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Migraine is a neurological disease characterized by severe and recurrent headaches. Children and adolescents with migraine often present to the emergency department (ED) with acute attacks, where migraine accounts for up to ~30% of all pediatric ED visits for headache. Based on the limited evidence, many centers have adopted protocols whereby children and adolescents who visit the ED with acute attacks of migraine are treated with an IV neuroleptic (metoclopramide or prochlorperazine) and an IV non-steroidal anti-inflammatory (ketorolac). This combination of interventions is largely considered to be standard of care despite no rigorous evidence to support this practice. Side effect rates with the neuroleptics (metoclopramide or prochlorperazine) are considerable. Therefore, the current standard of care for managing children and adolescents visiting the ED with acute attacks of migraine poses concern to patients and is associated with significant pain and frequent side effects.
Over the past few years, there has been a growth in research investigating the efficacy and safety of non-invasive neuromodulation for the management of acute attacks of migraine. At present, there are several commercially available, non-invasive neuromodulation devices that effectively and safely treat acute attacks of migraine in adults. Because none of these devices have a high level evidence in children, adolescents, nor in the ED setting, there is clinical equipoise as to which device would be most appropriate to study for treating children and adolescents visiting the ED with acute attacks. Throughout our patient engagement work, children and adolescents with migraine have identified that they are interested in trying remote electrical neuromodulation for treating migraine attacks in the ED.
The investigators completed a pilot randomized controlled trial (RCT) to determine the feasibility and acceptability of executing a phase III RCT, in which children and adolescents visiting the ED with acute attacks of migraine were randomized to REN or standard of care IV treatment. The trial had two phases: initially the design was a parallel-group design, and after 14 months of recruitment to that design, an amendment was made to allow participants to cross over to the other treatment arm if the initial intervention was not effective, in a crossover design. This change was made in response to participant and staff feedback around the parallel-group design.
One in ten Canadian children and adolescents suffer from migraine, and visits to the pediatric emergency department (ED) for acute attacks are common, with over 2,500 annual visits in Alberta alone. Evidence-based acute management options for children and adolescents presenting to the ED with acute attacks of migraine are limited. The current standard of care, which comprises a combination of a neuroleptic (metoclopramide) and a non-steroidal anti-inflammatory (ketorolac), has a low level of evidence and is administered through an intravenous (IV) cannula. However, at least half of children and adolescents presenting to the ED with acute attacks of migraine would prefer to avoid an IV, and these standard of care migraine interventions have substantial side effects and costs. The Nerivio remote electrical neuromodulation (REN) device is a novel, non-invasive, wearable REN device that is applied to the arm using an armband and wirelessly controlled by a smartphone software application. REN has established efficacy and safety for the treatment of acute attacks of migraine in adults, and preliminary open-label efficacy and safety data for use in adolescents. Through user engagement efforts, the investigators have identified that children and adolescents with migraine and ED providers are interested in trying REN to treat refractory acute attacks in the ED.
The investigators completed a pilot randomized controlled trial (RCT) that aimed to determine the feasibility and acceptability of implementing a phase III RCT, in which children and adolescents visiting the ED with acute attacks of migraine were randomized to REN, or to standard of care IV treatment in a double-dummy parallel group design phase, followed by a crossover design phase. During the crossover phase, participants were crossed over to the other treatment arm if the initial intervention is not effective. The objectives of the investigators were:
The investigators employed a pilot RCT to determine the feasibility and acceptability of implementing a double-dummy, parallel and crossover RCT protocol. The controlled trial was completed with two design phases: 1) a parallel-group phase from February 22, 2022 to May 15, 2023, and 2) a crossover design phase from May 16, 2023 to March 1, 2024. The design was switched to a crossover design mid-way through the trial based on feedback from participants and clinical staff around concerns with not being able to receive typical care in a timely manner if randomized to the REN arm in the parallel-group design.
In this pilot study, children and adolescents visiting the ED with acute attacks of migraine were randomized to initially receive either REN or standard of care IV treatment (i.e. a combination of metoclopramide and ketorolac). Each group also received a blinded control (either normal saline through the IV for the REN group, or sham stimulation for the standard of care IV group). Consenting participants were randomized at a 1:1 ratio to either REN or standard of care IV treatment. The allocation sequence was sent to the research pharmacy and was not accessible to anyone involved in the study or patient care. The REN group received active stimulation and normal saline placebo that appeared identical in appearance and volume to the medications given to the comparison group. The comparison group received a combination of pharmaceutical interventions considered to be the standard of care for treating children and adolescents visiting the ED with migraine: IV metoclopramide and IV ketorolac. The comparison group also received sham stimulation that was low enough that it did not induce conditioned pain modulation, the mechanism of action of REN, but it was perceptible and similar to the sensation induced by the REN device. Stimulation for both groups occurred over 45 minutes. In the crossover design phase, participants were assessed 120 minutes following the initial intervention and were crossed over to the other treatment arm if the initial intervention was not effective. Efficacy and safety outcomes were measured at baseline, 60 minutes, and 120 minutes (for both the initial and crossover study interventions as applicable), as well as 48 hours post-intervention.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard-of-Care IV Group | Other | Patients randomised to the standard of care IV group will receive a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
|
| REN Group | Other | Patients randomised to the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketorolac | Drug | Intervention in syringe for target dose of 0.5 mg/kg, maximum 30 mg of ketorolac (1 mL), and administer as a direct IV push over 1-5 minutes |
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| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Recruitment Rate | The primary outcome for this pilot study involves assessment of the feasibility of using the REN device to treat children and adolescents suffering from acute migraine attacks in the ED. The primary feasibility outcome will be determined based on the recruitment rate, defined as the number of participants enrolled per month. Our target is to have an average recruitment rate of 1.5 participants per month. Feasibility will be used as the primary outcome, along with the secondary outcomes, to provide preliminary data to help design and optimize a fully powered, phase III RCT. Recruitment rate for both phases of the study are reported to understand if changing to crossover design improved recruitment. We switched to a crossover design strictly to address participant and recruitment concerns around not receiving standard of care migraine treatment if initially randomized to receive REN treatment and such treatment was unsuccessful. | Evaluated monthly and at the end of recruitment (i.e., 2 years or once the final participant has completed the study) |
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in Pain Severity | Reduction in pain severity between baseline and 1-hour, 2 hours, and 48 hours post-interventions. Pain measured on an 11-point Likert scale where 0 = no pain and 10 = worst pain possible, with lower values indicating no/less pain and higher values indicating more pain. Headache pain was only assessed at 48 hours if participants indicated they were currently experiencing a headache and the 48 hours reduction in pain severity outcome does not include participants who crossed over and were exposed to both interventions as we expected them to become unblinded after being exposed to both study treatments; Standard of Care (Initial Treatment) n = 7, REN (Initial Treatment) n = 5. |
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Inclusion Criteria:
Patients aged 8-18 years visiting the Alberta Children's Hospital Emergency Department (ED) with an acute attack of migraine as per criteria B-E of the International Classification of Headache Disorders-3 criteria (ICHD-3):
B. Headache attacks lasting at least 2 hours (untreated or unsuccessfully treated)
C. Headache has at least two of the following four characteristics:
D. Also has least one of the following:
E. Not better accounted for by another diagnosis in the opinion of the treating physician
Criterion A (at least 5 attacks) is not being used in this study because prior research has shown that removing criterion A increases the sensitivity of these criteria in the ED. The patient and their caregiver will also be required to understand spoken and written English. In addition, potential participants will be required to have an upper arm circumference of at least 20 cm to ensure optimal device fit and safety.
Exclusion Criteria:
Exclusion criteria include the following: allergy or contraindication to metoclopramide, ketorolac, or non-steroidal anti-inflammatories; implanted electrical device, congestive heart failure, severe cardiac or cerebrovascular disease, uncontrolled epilepsy (2 or more unprovoked seizures per year), abnormal skin on both upper arms (e.g., cancerous lesion on both upper arms, metallic implants on both upper arms, or abnormal physical sensation in both upper arms), febrile at triage, head trauma in the past 7 days, current secondary headache, previously enrolled in the study, pregnant or lactating.
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| Name | Affiliation | Role |
|---|---|---|
| Serena L Orr, MD, MSc, FRCPC | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39290050 | Derived | Orr SL, Kuziek J, Ali S, Anderson E, Birnie KA, Hershey AD, Khanna P, Kirton A, Sajobi T, Freedman SB. Remote electrical neuromodulation to treat children and adolescents with migraine in the emergency department: A randomized double-dummy pilot trial. Headache. 2025 Jun;65(6):1015-1026. doi: 10.1111/head.14838. Epub 2024 Sep 17. |
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During the parallel-group phase, 3 participants provided written informed consent but withdrew prior to being randomized. As such, 22 participants were enrolled in the entire study but 19 of those were randomized to a study treatment. During the crossover phase, participants were not required to receive the crossover treatment if well enough to go home after the initial treatment. Only 2 participants received the crossover treatment (both REN initially and Standard of Care as crossover).
We employed a double-dummy, double-blind, pilot randomized controlled trial initially as a parallel-group design (February 22, 2022 to May 15, 2023), but switched to a crossover design (May 16, 2023 to March 1, 2024) to address participant concerns about not getting typical IV treatment if REN unsuccessful. Receiving the crossover treatment was not required as per protocol. The trial was carried out in a tertiary care pediatric ED at the Alberta Children's Hospital in Calgary, Alberta, Canada.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard-of-Care IV Group (Parallel Design Phase) | Patients recruited during the parallel phase and randomised to the standard of care IV group will receive a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg and 0.15 mg/kg, respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. Ketorolac: Intervention in syringe for target dose of 0.5 mg/kg, maximum 30 mg of ketorolac (1 mL), and administer as a direct IV push over 1-5 minutes Metoclopramide: Intervention in 50 mL mini bag of normal saline (0.9% NaCl) for target dose of 0.15 mg/kg, maximum 10 mg of metoclopramide (2 mL), and administer as infusion over 15-30 minutes Sham Remote Electrical Neuromodulation Device: The sham REN device is identical to the active REN device but the stimulation parameters are different, administering a modulated symmetrical biphasic square electrical pulse, modulated frequency of ~0.083 Hz and a modulated pulse width of 40-550 µ. These sham parameters are designed to induce a sensation that will be perceptible to participants, similar to stimulation from the active REN device, but at a frequency that is low enough so as to not modulate the nociceptive sensory nerves. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 10, 2023 |
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The investigators will carry out a pilot randomized controlled trial (RCT) to determine the feasibility and acceptability of implementing a double-dummy, parallel and crossover RCT protocol. The parallel-group phase was completed from February 22, 2022 to May 15, 2023, and the crossover design phase was completed from May 16, 2023 to March 1, 2024.
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Participants, research staff, and clinical staff, including the investigator, research assistant, research nurse, and attending physician, will remain blind to the study interventions.
|
| Metoclopramide | Drug | Intervention in 50 mL mini bag of normal saline (0.9% NaCl) for target dose of 0.15 mg/kg, maximum 10 mg of metoclopramide (2 mL), and administer as infusion over 15-30 minutes |
|
|
| Active Remote Electrical Neuromodulation Device | Device | The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. |
|
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| Placebo | Drug | 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
|
|
| Sham Remote Electrical Neuromodulation Device | Device | The sham REN device is identical to the active REN device but the stimulation parameters are different, administering a modulated symmetrical biphasic square electrical pulse, modulated frequency of ~0.083 Hz and a modulated pulse width of 40-550 µ. These sham parameters are designed to induce a sensation that will be perceptible to participants, similar to stimulation from the active REN device, but at a frequency that is low enough so as to not modulate the nociceptive sensory nerves. |
|
|
| Difference between baseline and 1 hour, 2 hours, and 48 hours post-intervention. |
| Number of Eligible Participants Who Are Screened, Enrolled, and Complete All Assessments | This secondary feasibility outcome involves the following: The number of participants who complete all assessments at each time point (baseline, 60, 120 minutes or at discharge if before 120 minutes, and 48-hours; for both the initial assigned intervention and the crossover intervention where applicable). | Evaluated monthly and at the end of recruitment (i.e., 2 years or once the final participant has completed the study) |
| Global Impression of Change | This acceptability outcome involves the following:
| Evaluated for each participant at 2-hours post-intervention, and 48-hours post-intervention |
| Study Feedback From Participants and Staff | This acceptability outcome involves the following: - Participant feedback regarding study acceptability. Participant feedback measured on 5-point Likert scale (1 = strongly disagree, 5 = strongly agree), where higher values indicate agreement and lower values indicate disagreement. Feedback questions related to study treatments is reported for both treatment groups and combined across treatment groups. Feedback questions related to the research staff and overall study experience is only combined and reported across both groups, rather than being reported for each group separately since these questions don't relate to specific study treatments. Feedback from clinical staff was collected after each participant's enrollment but not analyzed as this feedback was free-form and not collected using a scale. | Participant feedback evaluated at 48 hours post-intervention |
| Number of Participants Reporting Pain Freedom | Number of participants who indicated they were pain free 2-hours post-intervention. Pain measured on an 11-point Likert scale where 0 = no pain and 10 = worst pain possible, with lower values indicating no/less pain and higher values indicating more pain. | 2 hours post-intervention |
| Number of Participants Reporting Sustained Pain Freedom | Number of participants who indicated they were pain free 2-hours post-intervention and again 48-hours post-intervention. Pain measured on an 11-point Likert scale where 0 = no pain and 10 = worst pain possible, with lower values indicating no/less pain and higher values indicating more pain. | 48 hours post-intervention |
| Numbers of Participants Reporting a Change in 4-point Pain Severity Scale Between Baseline and 2 Hours Post-intervention | Number of participants who experienced a pain reduction from "severe" or "moderate" severity down to a "mild" or "no pain" severity, or those participants who experienced a pain reduction from "mild" to "no pain" severity between baseline and 2 hours post-intervention. Measured using the 4-point pain severity scale where 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe. Smaller values indicate no/less severe pain and higher values indicate more severe pain. | 2 hours post-intervention |
| Number of Participants Reporting Sustained Pain Relief | Change from baseline "moderate" to "severe pain" to "mild or "no pain", or change from baseline "mild pain" to "no pain" 2 hours post-intervention, which is sustained to 48 hours post-intervention. Measured using the 4-point pain severity scale where 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe. Smaller values indicate no/less severe pain and higher values indicate more severe pain. Participants who reported they did not have a headache between 2 hours and 48 hours post-intervention were not asked to rate their pain severity and were considered to have no headache pain at 48 hours. | 48 hours post-intervention |
| Number of Participants Reporting Adverse Events | The number of participants who reported experiencing adverse events and serious adverse events following intervention | Evaluated from time of intervention to 2 hours and 48 hours post-intervention |
| Number of Participants Reporting Freedom From Most Bothersome Symptom | The number of participants who experienced freedom from their most bothersome symptom (nausea, vomiting, sensitivity to light, or sensitivity to sound). | 2 hours post-intervention |
| Number of Participants Discharged From the Emergency Department With no Further Intervention | The number of participants discharged from the emergency department with no further intervention other than study intervention | 2 hours post-intervention (after last intervention, following ED discharge) |
| FG001 | REN Group (Parallel Design Phase) | Patients recruited during the parallel phase and randomised to the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| FG002 | Standard-of-Care IV Group First, Then REN Group if Applicable (Crossover Design Phase) | Patients recruited during the crossover phase and initially randomised to the standard of care IV group during the crossover phase will receive a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. At 120-minutes following the initial study intervention, participants will be assessed to see if they feel ready to go home or if they would like to receive the study treatment they did not initially receive(i.e., treatment from the REN Group). This would be a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. The crossover treatment is not required if the participant is considered well enough to go home (as per protocol). |
| FG003 | REN Group First, Then Standard-of-Care IV Group First if Applicable (Crossover Design Phase) | Patients recruited during the crossover phase and initially randomised to the REN group during the crossover phase will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. At 120-minutes following the initial study intervention, participants will be assessed to see if they feel ready to go home or if they would like to receive the study treatment they did not initially receive(i.e., treatment from the Standard-of-Care Group). This would be a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. The crossover treatment is not required if the participant is considered well enough to go home (as per protocol). |
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Baseline characteristics are reported per arm/group, separately for the parallel phase and crossover phase. No participants received the REN crossover treatment during the crossover phase as they were well enough to go home after the initial IV treatment (as per protocol). Both participants in the "REN Group First" arm of the crossover phase also received the SoC crossover treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard-of-Care IV Group (Parallel Design Phase) | Patients recruited during the parallel phase and randomised to the standard of care IV group will receive a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg and 0.15 mg/kg, respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. Ketorolac: Intervention in syringe for target dose of 0.5 mg/kg, maximum 30 mg of ketorolac (1 mL), and administer as a direct IV push over 1-5 minutes Metoclopramide: Intervention in 50 mL mini bag of normal saline (0.9% NaCl) for target dose of 0.15 mg/kg, maximum 10 mg of metoclopramide (2 mL), and administer as infusion over 15-30 minutes Sham Remote Electrical Neuromodulation Device: The sham REN device is identical to the active REN device but the stimulation parameters are different, administering a modulated symmetrical biphasic square electrical pulse, modulated frequency of ~0.083 Hz and a modulated pulse width of 40-550 µ. These sham parameters are designed to induce a sensation that will be perceptible to participants, similar to stimulation from the active REN device, but at a frequency that is low enough so as to not modulate the nociceptive sensory nerves. |
| BG001 | REN Group (Parallel Design Phase) | Patients recruited during the parallel phase and randomised to the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| BG002 | Standard-of-Care IV Group First, Then REN Group if Applicable (Crossover Design Phase) | Patients recruited during the crossover phase and initially randomised to the standard of care IV group during the crossover phase will receive a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. At 120-minutes following the initial study intervention, participants will be assessed to see if they feel ready to go home or if they would like to receive the study treatment they did not initially receive(i.e., treatment from the REN Group). This would be a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. The crossover treatment is not required if the participant is considered well enough to go home (as per protocol). |
| BG003 | REN Group First, Then Standard-of-Care IV Group First if Applicable (Crossover Design Phase) | Patients recruited during the crossover phase and initially randomised to the REN group during the crossover phase will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. At 120-minutes following the initial study intervention, participants will be assessed to see if they feel ready to go home or if they would like to receive the study treatment they did not initially receive(i.e., treatment from the Standard-of-Care Group). This would be a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. The crossover treatment is not required if the participant is considered well enough to go home (as per protocol). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age group of participants. Due to the inclusion and exclusion criteria, participants had to be between 8.00 and 18.00 years of age. | Count of Participants | Participants |
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| Age, Continuous | Reported age of all participants who were enrolled and completed study treatment. Standard-of-Care Group: Range = 11 to 17 years REN Group: Range = 13 to 17 years | Mean | Standard Deviation | years |
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| Sex: Female, Male | Sex of participants as recorded by the research nurse. Question wording: "Participant sex (what sex was assigned at birth)". Potential responses = Male, Female, Other | Count of Participants | Participants |
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| Race (NIH/OMB) | Race as reported by participants. Question wording: "Are you:". Possible responses: White, South Asian (e.g., East Indian, Pakistani, Sri Lankan), Chinese, Black, Filipino, Arab, Latin American, Southeast Asian (e.g., Vietnamese, Cambodian, Laotian, Thai), West Asian, Korean, Japanese, Other | Count of Participants | Participants |
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| Region of Enrollment | Region participants were recruited from. All participants were recruited exclusively in Canada. | Number | participants |
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| Current attack baseline pain severity | 11-point (0-10) pain numerical rating as reported by the participant. Question wording: "On a scale of 0 to 10, what is the level of your pain for this headache?" | Median | Inter-Quartile Range | units on a scale |
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| Current attack duration in hours | Duration of the current migraine attack (converted to "hours") as reported by the participant. Questions wording: "How long has the participant had this headache for?" | Median | Inter-Quartile Range | Hours |
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| Current attack with aura | Number of participants who report having an aura with the current migraine attack. Question wording: "Did the participant have any auras (warnings) that today's headache was going to start?" | Count of Participants | Participants |
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| History of prior attacks with aura | Number of participants who reported having a history of aura with their migraine attacks. Question wording: "Does the participant have any auras (warnings) that the headache is going to start?" | Count of Participants | Participants |
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| Headache frequency in days/month | Frequency of migraine attacks (days per month) as reported by participants. Exact question: "How many days per month does the participant have ANY headaches?" | Median | Inter-Quartile Range | Days per Month |
| ||||||||||||||
| Number of participants with continuous headache at baseline | Number of participants who reported having a continuous headache (reported "Daily" or "Always"). Question wording: "How often do the participant's headaches occur" Potential responses: < 1/month, 1-3/month, 1/week, 2-3/week, 4-6/week, Daily, Always, N/A, this is participant's first headache ever, Other | Count of Participants | Participants |
| |||||||||||||||
| Number of past headache-related ED visits | Numbers of headache-related emergency department visits reported by the participant. Only asked to participants who indicate "Yes" to the question "Has the participant been to the emergency department for headache in the past?" Question wording: "How many times has the participant been to the emergency department for headache in the past 2 years?" Potential responses: 1, 2, 3, 4, 5, 6 or more | Number | Counts |
| |||||||||||||||
| Took acute intervention at home prior to ED visit | Number of participants who reported taking any acute intervention(s) at home for their current migraine attack. Question wording: "What pain medication(s) did you take at home for this headache?" | Count of Participants | Participants |
| |||||||||||||||
| On a migraine preventive intervention at home | Number of participants who are currently taking any preventive intervention(s) at home. Question wording: "What medication(s) or nutraceutical(s) is the participant currently using to PREVENT headaches?" | Count of Participants | Participants |
| |||||||||||||||
| PedMIDAS Score | Summed score of the Pediatric Migraine Disability Assessment (PedMIDAS) headache disability questionnaire, as completed by participants. The PedMIDAS aims to assess the degree of migraine-related disability in children and adolescents with headache. It is a 6-item scale whereby patients are asked to quantify the number of days of reduced attendance and functioning in the academic, home and extracurricular spheres over the past three months. Minimum score = 0, Maximum score = 240. Larger scores indicate greater migraine-related disability. | Median | Inter-Quartile Range | units on a scale |
| ||||||||||||||
| Duration of time with headaches in months | How long participants report having any headaches (in months). Question wording: "How long has the participant had any type of headache?" | Median | Inter-Quartile Range | Months |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Assessment of Recruitment Rate | The primary outcome for this pilot study involves assessment of the feasibility of using the REN device to treat children and adolescents suffering from acute migraine attacks in the ED. The primary feasibility outcome will be determined based on the recruitment rate, defined as the number of participants enrolled per month. Our target is to have an average recruitment rate of 1.5 participants per month. Feasibility will be used as the primary outcome, along with the secondary outcomes, to provide preliminary data to help design and optimize a fully powered, phase III RCT. Recruitment rate for both phases of the study are reported to understand if changing to crossover design improved recruitment. We switched to a crossover design strictly to address participant and recruitment concerns around not receiving standard of care migraine treatment if initially randomized to receive REN treatment and such treatment was unsuccessful. | Number of participants who were screened, deemed eligible, and subsequently enrolled. Three (3) participants during the parallel-group design phase withdrew after consent but before being randomized/receiving study treatments. No other participants withdrew during the study. | Posted | Mean | Standard Deviation | participants per month | Evaluated monthly and at the end of recruitment (i.e., 2 years or once the final participant has completed the study) |
|
|
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| Secondary | Reduction in Pain Severity | Reduction in pain severity between baseline and 1-hour, 2 hours, and 48 hours post-interventions. Pain measured on an 11-point Likert scale where 0 = no pain and 10 = worst pain possible, with lower values indicating no/less pain and higher values indicating more pain. Headache pain was only assessed at 48 hours if participants indicated they were currently experiencing a headache and the 48 hours reduction in pain severity outcome does not include participants who crossed over and were exposed to both interventions as we expected them to become unblinded after being exposed to both study treatments; Standard of Care (Initial Treatment) n = 7, REN (Initial Treatment) n = 5. | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Mean | Standard Deviation | units on a scale | Difference between baseline and 1 hour, 2 hours, and 48 hours post-intervention. |
| ||||||||||||||||||||||||||||||
| Secondary | Number of Eligible Participants Who Are Screened, Enrolled, and Complete All Assessments | This secondary feasibility outcome involves the following: The number of participants who complete all assessments at each time point (baseline, 60, 120 minutes or at discharge if before 120 minutes, and 48-hours; for both the initial assigned intervention and the crossover intervention where applicable). | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | Evaluated monthly and at the end of recruitment (i.e., 2 years or once the final participant has completed the study) |
| |||||||||||||||||||||||||||||||
| Secondary | Global Impression of Change | This acceptability outcome involves the following:
| Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Number | participants | Evaluated for each participant at 2-hours post-intervention, and 48-hours post-intervention |
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| Secondary | Study Feedback From Participants and Staff | This acceptability outcome involves the following: - Participant feedback regarding study acceptability. Participant feedback measured on 5-point Likert scale (1 = strongly disagree, 5 = strongly agree), where higher values indicate agreement and lower values indicate disagreement. Feedback questions related to study treatments is reported for both treatment groups and combined across treatment groups. Feedback questions related to the research staff and overall study experience is only combined and reported across both groups, rather than being reported for each group separately since these questions don't relate to specific study treatments. Feedback from clinical staff was collected after each participant's enrollment but not analyzed as this feedback was free-form and not collected using a scale. | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Mean | Standard Deviation | units on a scale | Participant feedback evaluated at 48 hours post-intervention |
| ||||||||||||||||||||||||||||||
| Secondary | Number of Participants Reporting Pain Freedom | Number of participants who indicated they were pain free 2-hours post-intervention. Pain measured on an 11-point Likert scale where 0 = no pain and 10 = worst pain possible, with lower values indicating no/less pain and higher values indicating more pain. | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | 2 hours post-intervention |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants Reporting Sustained Pain Freedom | Number of participants who indicated they were pain free 2-hours post-intervention and again 48-hours post-intervention. Pain measured on an 11-point Likert scale where 0 = no pain and 10 = worst pain possible, with lower values indicating no/less pain and higher values indicating more pain. | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | 48 hours post-intervention |
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| Secondary | Numbers of Participants Reporting a Change in 4-point Pain Severity Scale Between Baseline and 2 Hours Post-intervention | Number of participants who experienced a pain reduction from "severe" or "moderate" severity down to a "mild" or "no pain" severity, or those participants who experienced a pain reduction from "mild" to "no pain" severity between baseline and 2 hours post-intervention. Measured using the 4-point pain severity scale where 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe. Smaller values indicate no/less severe pain and higher values indicate more severe pain. | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | 2 hours post-intervention |
| |||||||||||||||||||||||||||||||
| Secondary | Number of Participants Reporting Sustained Pain Relief | Change from baseline "moderate" to "severe pain" to "mild or "no pain", or change from baseline "mild pain" to "no pain" 2 hours post-intervention, which is sustained to 48 hours post-intervention. Measured using the 4-point pain severity scale where 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe. Smaller values indicate no/less severe pain and higher values indicate more severe pain. Participants who reported they did not have a headache between 2 hours and 48 hours post-intervention were not asked to rate their pain severity and were considered to have no headache pain at 48 hours. | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | 48 hours post-intervention |
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| Secondary | Number of Participants Reporting Adverse Events | The number of participants who reported experiencing adverse events and serious adverse events following intervention | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | Evaluated from time of intervention to 2 hours and 48 hours post-intervention |
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| Secondary | Number of Participants Reporting Freedom From Most Bothersome Symptom | The number of participants who experienced freedom from their most bothersome symptom (nausea, vomiting, sensitivity to light, or sensitivity to sound). | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | 2 hours post-intervention |
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| Secondary | Number of Participants Discharged From the Emergency Department With no Further Intervention | The number of participants discharged from the emergency department with no further intervention other than study intervention | Treatment data are combined across phases, separated based on treatment given and time given to be consistent with how we specified results would be reported in the protocol (i.e., "...for both the initial assigned intervention and the crossover intervention where applicable"). Participants who received SoC IV at crossover received REN initially, and vice versa. No participants received REN crossover treatment as they were well enough to go home after the initial IV treatment (as per protocol). | Posted | Count of Participants | Participants | 2 hours post-intervention (after last intervention, following ED discharge) |
|
Adverse events were monitored and recorded from the start of study treatment administration until completion of the 48-hour follow-up.
Any symptom, sign, illness or experience that develops or worsens in severity during the study, including intercurrent illnesses or injuries. Abnormal results of diagnostic tests are considered if it:
No participants received REN as the crossover treatment during the crossover phase.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard-of-Care IV (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the standard of care IV group will receive a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. Ketorolac: Intervention in syringe for target dose of 0.5 mg/kg, maximum 30 mg of ketorolac (1 mL), and administer as a direct IV push over 1-5 minutes Metoclopramide: Intervention in 50 mL mini bag of normal saline (0.9% NaCl) for target dose of 0.15 mg/kg, maximum 10 mg of metoclopramide (2 mL), and administer as infusion over 15-30 minutes Sham Remote Electrical Neuromodulation Device: The sham REN device is identical to the active REN device but the stimulation parameters are different, administering a modulated symmetrical biphasic square electrical pulse, modulated frequency of ~0.083 Hz and a modulated pulse width of 40-550 µ. These sham parameters are designed to induce a sensation that will be perceptible to participants, similar to stimulation from the active REN device, but at a frequency that is low enough so as to not modulate the nociceptive sensory nerves. | 0 | 10 | 0 | 10 | 1 | 10 |
| EG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. | 0 | 9 | 0 | 9 | 0 | 9 |
| EG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. Participants are assessed 2-hours after the initial study treatment and, if they indicate they are not well enough to go home, they are given the crossover treatment. When participants indicate that they feel well enough to go home after initial study treatments, they are not given the crossover treatment. | 0 | 2 | 0 | 2 | 0 | 2 |
| EG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Participants are assessed 2-hours after the initial study treatment and, if they indicate they are not well enough to go home, they are given the crossover treatment. When participants indicate that they feel well enough to go home after initial study treatments, they are not given the crossover treatment. Because all participants randomized to the standard of care IV group for initial treatment felt well enough to go home after initial treatment, no participants received the REN crossover treatment and no participants in this group were at risk for adverse events during this phase of the study. | 0 | 0 | 0 | 0 | 0 | 0 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Akathisia | Nervous system disorders | Systematic Assessment | Physical/mental restlessness |
|
Our study was conducted during the COVID19 pandemic, the Fall of 2022 "tripledemic", and a shiga-toxin E. Coli outbreak. These events hampered recruitment and our recruitment estimate is likely lower than what we anticipate under 'normal' conditions. Due to delays in the approval process, we had a shorter crossover than the parallel-group phase (9 vs. 15 months). Lastly, 90% of our study participants were White, as such the generalizability of our results is limited.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Serena Orr | University of Calgary/Alberta Health Services | 403-955-7728 | serena.orr@albertahealthservices.ca |
| Sep 3, 2024 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D004630 | Emergencies |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D020910 | Ketorolac |
| D020911 | Ketorolac Tromethamine |
| D008787 | Metoclopramide |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D007213 | Indomethacin |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D062366 | para-Aminobenzoates |
| D062365 | Aminobenzoates |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D002723 | Chlorobenzoates |
| D062425 | Hydroxybenzoate Ethers |
| D062385 | Hydroxybenzoates |
| D006880 | Hydroxy Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010647 | Phenyl Ethers |
| D010636 | Phenols |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 1 |
|
| 2 |
|
| 3 |
|
| 4 |
|
| 5 |
|
| >=6 |
|
| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. Participants are assessed 2-hours after the initial study treatment and, if they indicate they are not well enough to go home, would be given the crossover treatment. As such, the crossover treatment was not required. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Participants are assessed 2-hours after the initial study treatment and, if they indicate they are not well enough to go home, would be given the crossover treatment. As such, the crossover treatment was not required. |
|
|
| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
|
|
| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
|
|
| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
| OG004 | All Participants | Participants from both SoC and REN treatment groups. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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| OG001 | REN (Initial Treatment; Parallel and Crossover Phases) | Patients randomised to initially receive the REN group will receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and will also receive two doses of normal saline though an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. Active Remote Electrical Neuromodulation Device: The REN device is a battery-powered, wirelessly controlled neuromodulation device that attaches via armband to the upper arm. The REN device is controlled by a smartphone application and administers electrical stimulation to the local C and Aδ nociceptive sensory nerves of the upper arm. This stimulation is achieved using a symmetrical, biphasic, square pulse, modulated at a frequency between 100-120 Hz. Each pulse has a width of 400 µs and the user, via the smartphone application, can adjust the output current to apply a maximum of 40 mA. Each stimulation session occurs over 45 minutes and each device can administer up to 12 stimulation sessions. Placebo: 0.9% NaCl will be administered to participants through IV in identical dosages, methods, and duration as the ketorolac and metoclopramide interventions described above. |
| OG002 | Standard-of-Care IV (Crossover Treatment; Crossover Phase) | Patients who initially received stimulation from the REN device and two doses of saline, and then crossed over to receive the standard of care IV and a single, 45-minute stimulation from a sham remote electrical neuromodulation (REN) device, which will not administer the typical electrical stimulation (modulated frequency of ~ 0.083 Hz and a modulated pulse width of 40-550 µs), and will be given a single dose IV ketorolac and IV metoclopramide, at a dose of 0.5 mg/kg (for a maximum 30 mg) and 0.15 mg/kg (for a maximum 10mg), respectively. Metoclopramide will be infused over 15-30 minutes and ketorolac will be administered as a direct IV push over 1-5 minutes. |
| OG003 | REN (Crossover Treatment; Crossover Phase) | Patients randomised to initially receive the Standard of Care IV and stimulation from the sham REN device, and then crossed over to receive a single 45-minutes stimulation from the REN device (modulated frequency of 100-120 Hz and a pulse width of 400 µs) and two doses of normal saline through an IV. Two doses of saline will be used to match the dosage, route of administration, and duration to ketorolac and metoclopramide, as described above in the standard-of-care IV group. |
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