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This is a Post-marketing study investigating the safety and efficacy of the REN device (Nerivio by Theranica, Israel) in adolescents with migraine. Data analysis concerning the REN treatment efficacy in terms of pain and functional disability as a standalone treatment or in combination with other medications will be performed.
The REN device (Nerivio by Theranica, Israel) is a neuromodulation device approved by the FDA for acute treatment of migraine in patients of 12 years old and above (1-4). It is a wearable device applied to the upper arm. It stimulates C and Aδ noxious fibers using a modulated, symmetrical, biphasic, square pulse with a pulse width of 400 μs, modulated frequency of 100-120 Hz, and up to 40 mA output current which the patient can adjust. The REN device is operated by a designated app that is downloaded to the user's phone prior first use of the Nerivio device
As part of the sign-up process to the Nerivio app, all patients accept the terms of use which specify that providing personal information is done of their own free will and that their de-identified data may be used for research purposes. Users are not obligated to provide personal information and could treat without providing any feedback. The app includes a secured, personal migraine diary, which enables patients to record and track their migraines and other headaches. At the beginning of each treatment, and again 2 hours after the start of treatment, patients are prompted to record their symptoms, including pain level (none, mild, moderate, severe), functional disability (No limitation, Some limitation, Moderate limitation, Severe limitation), and an indication of which medications, if any, were taken within that 2-hour time window.
Post-marketing surveillance is designed to assess the efficacy and safety in larger and more diverse populations and in various real-world environments and situations. As a digital therapeutic device (i.e., electroceutical), the REN device enables prospective collection of electronic patient-reported outcomes in real-world clinical practice.
Recently, Real World Evidence (RWE) papers of Nerivio usage in adults were published (5-6). these papers demonstrated the safety and efficacy of the Nerivio device in a large-scale population using the accumulated data gathered by diary within the Nerivio app.
This post-marketing RWE study investigates the efficacy of the Nerivio treatment using the following outcomes:
Together, these four objectives provide a comprehensive evaluation of efficacy, drug-device interactions, dose stability, and safety, in a large real-world dataset of over XXXXX treatments in the migraine adolescent population.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nerivio | Device | Remote electrical neuromodulation (REN) device for the acute treatment of migraines. The device delivers transcutaneous electrical stimulation to the upper arm to induce conditioned pain modulation(CPM) that activates a descending endogenous analgesic mechanism. The treatment is self-administered and controlled by a smartphone application. |
| Measure | Description | Time Frame |
|---|---|---|
| Consistent Pain Relief at 2 Hours Post-treatment | The proportion of subjects reporting pain relief at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. Pain relief is defined as an improvement from severe or moderate pain to mild or no pain, Pain level is reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain,3- Severe pain) | 2 hours post treatment, up to 16 months from the 1st treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Consistent Pain Freedom at 2 Hours Post-treatment | The proportion of subjects reporting freedom from pain at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. Pain freedom is defined as reduction from severe or moderate or mild pain to no pain, Pain level is reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain,3- Severe pain) |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Intensity Distribution | The mean intensity of the stimulation collected for all treatments that were performed within the study | 45 minutes post treatment, up to 16 months from the 1st treatment |
| Device Related Adverse Events |
Inclusion Criteria:
Exclusion Criteria:
(1) - Treatments shorter than 20 minutes
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Adolescence (age 12-18) who suffers from migraine who are using the Nerivio device for acute treatment of migraine
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| Name | Affiliation | Role |
|---|---|---|
| Alit Stark Inbar, PhD | Theranica Bio-Electronics ltd | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Theranica USA Inc | Bridgewater | New Jersey | 08807 | United States | ||
| Theranica Bio-Electronics Ltd |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31074005 | Background | Yarnitsky D, Dodick DW, Grosberg BM, Burstein R, Ironi A, Harris D, Lin T, Silberstein SD. Remote Electrical Neuromodulation (REN) Relieves Acute Migraine: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial. Headache. 2019 Sep;59(8):1240-1252. doi: 10.1111/head.13551. Epub 2019 May 9. | |
| 34138449 | Background |
| Label | URL |
|---|---|
| Results for NCT05443659 | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Nerivio Users Age 12-18 | Adolecents with migraine who used theNerivio REN device for treating theitr migraine |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Adolescents with migraine who used the Nerivio REN device for treatment of their migraine
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| ID | Title | Description |
|---|---|---|
| BG000 | Nerivio Users Age 12-18 | Adolecents with migraine who used the nerivio REN device for treating theitr migraine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age of participant at the day of creating a nerivio account |
| 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 | Consistent Pain Relief at 2 Hours Post-treatment | The proportion of subjects reporting pain relief at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. Pain relief is defined as an improvement from severe or moderate pain to mild or no pain, Pain level is reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain,3- Severe pain) | REN users at the age of 12-=18 who used the Nerivio device as a single therapy (without rescue treatments were used) and had at least two evaluable treatments (with data at T=0h and T=2h) and repoerted baseline headache of moderate or severe in T=0h | Posted | Count of Participants | Participants | 2 hours post treatment, up to 16 months from the 1st treatment |
|
up to 18 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nerivio Users Age 12-18 | Adolecents with migraine who used the nerivio REN device for treating theitr migraine |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tingling | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Dagan Harris, VP Clinical and Regulatory Affairs | Theranica | +972542220121 | daganh@theranica.com |
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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 | Jan 1, 2021 | Aug 17, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| 2 hours post treatment, up to 16 months from the 1st treatment |
| Consistent Usage of Migraine Abortive (Rescue) Medications | The proportion of subjects with REN treatments without the use of pharmacological migraine abortive (rescue) medication (either over the counter or prescribed), or with a combination of rescue medication or without any treatment at all at 2 hours post-treatment in at least 50% of all their treatments. | 2 hours post treatment, up to 16 months from the 1st treatment |
| Consistent Functional Disability Relief at 2 Hours Post-treatment | The proportion of subjects reporting Functional Disability (FD) relief at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. FD relief is defined as an improvement from severe or moderate limitation to some or no limitation. FD level is reported using a 4-point Likert scale (0 - No limitation, 1 - Some limitation, 2 - Moderate limitation, 3 - Severe limitation) | 2 hours post treatment, up to 16 months from the 1st treatment |
| Consistent Functional Disability Disappearance at 2 Hours Post-treatment | The proportion of subjects reporting no Functional Disability (FD) at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. FD disappearance is defined as an improvement from severe or moderate or limitation to no limitation. FD level is reported using a 4-point Likert scale (0 - No limitation, 1 - Some limitation, 2 - Moderate limitation, 3 - Severe limitation). | 2 hours post treatment, up to 16 months from the 1st treatment |
Incidence of device-related adverse events reported by subjects
| Up to 16 months |
| Netanya |
| 4250438 |
| Israel |
| Nierenburg H, Rabany L, Lin T, Sharon R, Harris D, Ironi A, Wright P, Chuang L. Remote Electrical Neuromodulation (REN) for the Acute Treatment of Menstrual Migraine: a Retrospective Survey Study of Effectiveness and Tolerability. Pain Ther. 2021 Dec;10(2):1245-1253. doi: 10.1007/s40122-021-00276-7. Epub 2021 Jun 17. |
| 34667919 | Background | Grosberg B, Rabany L, Lin T, Harris D, Vizel M, Ironi A, O'Carroll CP, Schim J. Safety and efficacy of remote electrical neuromodulation for the acute treatment of chronic migraine: an open-label study. Pain Rep. 2021 Oct 14;6(4):e966. doi: 10.1097/PR9.0000000000000966. eCollection 2021 Nov-Dec. |
| 33349920 | Background | Hershey AD, Lin T, Gruper Y, Harris D, Ironi A, Berk T, Szperka CL, Berenson F. Remote electrical neuromodulation for acute treatment of migraine in adolescents. Headache. 2021 Feb;61(2):310-317. doi: 10.1111/head.14042. Epub 2020 Dec 21. |
| 32935848 | Background | Tepper SJ, Lin T, Montal T, Ironi A, Dougherty C. Real-world Experience with Remote Electrical Neuromodulation in the Acute Treatment of Migraine. Pain Med. 2020 Dec 25;21(12):3522-3529. doi: 10.1093/pm/pnaa299. |
| 36931109 | Background | Esparham A, Stark-Inbar A, Jekel L, Tamir S, Rabany L, Ironi A, Gautreaux J, Rao R. Acute Treatment of Migraine in Adolescents: Real-World Analysis of Remote Electrical Neuromodulation (REN). Pediatr Neurol. 2023 May;142:51-55. doi: 10.1016/j.pediatrneurol.2023.02.008. Epub 2023 Feb 21. |
| 35295483 | Result | Ailani J, Rabany L, Tamir S, Ironi A, Starling A. Real-World Analysis of Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine. Front Pain Res (Lausanne). 2022 Jan 18;2:753736. doi: 10.3389/fpain.2021.753736. eCollection 2021. |
The age was calculated once per all study participants following by a subanalysis for each gender
| Mean |
| Standard Deviation |
| years |
|
| Sex/Gender, Customized | The gender of the participants (female, male, not identified) | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
|
|
| Secondary | Consistent Pain Freedom at 2 Hours Post-treatment | The proportion of subjects reporting freedom from pain at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. Pain freedom is defined as reduction from severe or moderate or mild pain to no pain, Pain level is reported using a 4-point Likert scale (0 - No pain, 1 - Mild pain, 2 - Moderate pain,3- Severe pain) | REN users at the age of 12-18 who used the Nerivio device as a single therapy (without rescue treatments were used) and had at least two evaluable treatments (with data at T=0h and T=2h) and reported a type of headache in T=0h and no headache in the T=2h questionnaire | Posted | Count of Participants | Participants | 2 hours post treatment, up to 16 months from the 1st treatment |
|
|
|
| Secondary | Consistent Usage of Migraine Abortive (Rescue) Medications | The proportion of subjects with REN treatments without the use of pharmacological migraine abortive (rescue) medication (either over the counter or prescribed), or with a combination of rescue medication or without any treatment at all at 2 hours post-treatment in at least 50% of all their treatments. | REN users at the age of 12-18 who used the Nerivio device as a single therapy (without rescue treatments were used) or with a combination of Nerivio and rescue medication or without any treatment at all and had at least two evaluable treatments (with data at T=0h and T=2h) | Posted | Count of Units | Treatments with reportad medication | 2 hours post treatment, up to 16 months from the 1st treatment | Treatments with reportad medication | Treatments with reportad medication |
|
|
|
| Secondary | Consistent Functional Disability Relief at 2 Hours Post-treatment | The proportion of subjects reporting Functional Disability (FD) relief at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. FD relief is defined as an improvement from severe or moderate limitation to some or no limitation. FD level is reported using a 4-point Likert scale (0 - No limitation, 1 - Some limitation, 2 - Moderate limitation, 3 - Severe limitation) | REN users at the age of 12-18 who used the Nerivio device as a single therapy (without rescue treatments were used) and had at least two evaluable treatments (with data at T=0h and T=2h) and reported a reduction of at least one grade in the functional disability scale at T=2h | Posted | Count of Participants | Participants | 2 hours post treatment, up to 16 months from the 1st treatment |
|
|
|
| Secondary | Consistent Functional Disability Disappearance at 2 Hours Post-treatment | The proportion of subjects reporting no Functional Disability (FD) at 2 hours post-treatment without the use of rescue medication in at least 50% of all their treatments. FD disappearance is defined as an improvement from severe or moderate or limitation to no limitation. FD level is reported using a 4-point Likert scale (0 - No limitation, 1 - Some limitation, 2 - Moderate limitation, 3 - Severe limitation). | REN users at the age of 12-18 who used the Nerivio device as a single therapy (without rescue treatments were used) and had at least two evaluable treatments (with data at T=0h and T=2h) and had a score of at least 1 in the functional disability scale and reported no functional disability at T=2h | Posted | Count of Participants | Participants | 2 hours post treatment, up to 16 months from the 1st treatment |
|
|
|
| Other Pre-specified | Treatment Intensity Distribution | The mean intensity of the stimulation collected for all treatments that were performed within the study | Nerivio users at the age of 12-18 who treated at least once with the Nerivio device | Posted | Count of Units | Nerivio treatments | 45 minutes post treatment, up to 16 months from the 1st treatment | Nerivio treatments | Nerivio treatments |
|
|
|
| Other Pre-specified | Device Related Adverse Events | Incidence of device-related adverse events reported by subjects | Nerivio users at the age of 12-18 who used the device at least once | Posted | Count of Participants | Participants | Up to 16 months |
|
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|
| 0 |
| 1,629 |
| 0 |
| 1,629 |
| 3 |
| 1,629 |
| Arm soreness | Nervous system disorders | Non-systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| Title | Measurements |
|---|---|
|
| reatments with Nerivio and other Rx |
|
| Title | Measurements |
|---|---|
|
| Intensity level 16-20 |
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| Intensity level 21-25 |
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| Intensity level 26-30 |
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| Intensity level 31-35 |
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| Intensity level 36-40 |
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| Intensity level 41-45 |
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| Intensity level 46-50 |
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| Intensity level 51-55 |
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| Intensity level 56-60 |
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| Intensity level 61-65 |
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| Intensity level 66-70 |
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| Intensity level 71-75 |
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| Intensity level 76-80 |
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| Intensity level 81-85 |
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| Intensity level 86-90 |
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| Intensity level 91-95 |
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| tensity level 96-100 |
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