Not provided
Not provided
Not provided
Not provided
Not provided
Difficulty recruiting participants
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The objective of this study is to compare clinical efficacy and tolerability of valproic acid (VPA) therapy versus dihydroergotamine (DHE) as abortive therapy in pediatric migraine.
The purpose of this study is to compare valproic acid (VPA) and dihydroergotamine (DHE) alone and sequentially in the treatment of pediatric migraines.
Inpatient pediatric migraine patients (based on International Classification of Headache Disorders, ICHD-II criteria) or those admitted to the University of Kentucky emergency department will receive standard of care acute headache management as per AAP/AAN guidelines. Those who fail to respond will be considered for further eligibility. Informed consent/assent will be obtained from the patients, parents or legal guardian.
Baseline labs will be collected prior to the start of the study.
Patients will initially be randomized into two groups (VPA or DHE) and treated for 24 hours. Those patients whose migraines resolve will end the study at 24 hours. Patients who are refractory to treatment will switch interventions and continue treatment for an additional 24 hours.
Intervention 1: VPA Intervention 2: DHE
Patients in Group 1 will be treated with VPA for 24 hours. They will be given an initial dose of IV VPA at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours; depending on drug levels they may also be checked at 8 and 12 hours. The target serum concentration is 100 (+/-10) ug/mL.
Patients in Group 2 will be treated with DHE for 24 hours. Dosing will be weight-based with no single dose >1mg and total 24 hour dose <3mg.
0 hour: 0.5 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.0 x (wt in kg) x (0.014) =Xmg
Patients will be assessed for migraine severity at baseline, 4, 8, 12, and 24 hours.
The endpoint criterion is successful migraine resolution (improvement in VAS and resolution of photophobia, phonophobia, and nausea). Patients meeting this criterion will not continue forward in the study.
At 24 hours, those patients that are refractory to treatment will cross over to the alternate intervention, i.e. patients receiving VPA first will then get DHE, and patients receiving DHE first will then get VPA. Outcomes will be measured for the next 24 hour period as described above.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Valproic Acid | Active Comparator | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. |
|
| Dihydroergotamine | Active Comparator | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. |
|
| Cross-Over to Dihydroergotamine | Active Comparator | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Patients who do not respond to VPA after 24 hours will be given Dihydroergotamine (DHE) for the next 24 hours. Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. |
|
| Cross-Over to Valproic Acid | Active Comparator | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Patients who do not respond to DHE after 24 hours will be given Valproic Acid (VPA) for the next 24 hours. An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Valproic Acid (VPA) | Drug | IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Pain Perception | Change in pain perception measured by the 10-point visual analogue scale (VAS), where 0 is "no pain" and 10 is "pain as bad as it could be." | Baseline to 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Presence of Photophobia | Presence of absence of photophobia | Baseline, 4, 8, 12 and 24 hours |
| Percentage of Participants With Presence of Phonophobia | Presence of absence of phonophobia |
Not provided
Inclusion Criteria:
Exclusion Criteria:
For Valproic Acid (VPA)
For Dihydroergotamine (DHE)
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kentucky | Lexington | Kentucky | 40536 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Valproic Acid | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours |
| FG001 | Dihydroergotamine | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| FG002 | Cross-Over to Dihydroergotamine | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Patients who do not respond to VPA after 24 hours will be given Dihydroergotamine (DHE) for the next 24 hours. Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| FG003 | Cross-Over to Valproic Acid | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Patients who do not respond to DHE after 24 hours will be given Valproic Acid (VPA) for the next 24 hours. An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
No participants where enrolled in the cross-over dihydroergotamine group.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Valproic Acid | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Change in Pain Perception | Change in pain perception measured by the 10-point visual analogue scale (VAS), where 0 is "no pain" and 10 is "pain as bad as it could be." | No participants were enrolled in the cross-over to dihydroergotamine arm. Participants were analyzed on a per-arm basis. Data were not collected for DHE only for the two participants who crossed over to Valproic Acid; only the combination of treatments. | Posted | Mean | Standard Deviation | change in score on a scale | Baseline to 24 hours |
|
Participants were assessed at baseline, 4 hour, 8 hour, 12, 24 hours per intervention.
No participants were enrolled in the cross-over to dihydroergotamine arm so there was no risk for all-cause mortality.
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 | Valproic Acid | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tightness in chest | Cardiac disorders | Non-systematic Assessment | Participant experienced chest tightness that resolved in 15 to 20 minutes |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kimberly Jones, MD | University of Kentucky | 859-218-5011 | kimberly.jones@uky.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Nov 27, 2018 | Aug 25, 2021 | Prot_SAP_ICF_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D008881 | Migraine Disorders |
| D006261 | Headache |
| ID | Term |
|---|---|
| D051270 | Headache Disorders, Primary |
| D020773 | Headache Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D014635 | Valproic Acid |
| D004087 | Dihydroergotamine |
| ID | Term |
|---|---|
| D010421 | Pentanoic Acids |
| D014631 | Valerates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Dihydroergotamine (DHE) | Drug | 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
|
| Baseline, 4, 8, 12 and 24 hours |
| Percentage of Participants With Presence of Nausea | Presence or absence of nausea | Baseline, 4, 8, 12 and 24 hours |
| BG001 | Dihydroergotamine | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| BG002 | Cross-Over to Dihydroergotamine | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Patients who do not respond to VPA after 24 hours will be given Dihydroergotamine (DHE) for the next 24 hours. Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| BG003 | Cross-Over to Valproic Acid | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Patients who do not respond to DHE after 24 hours will be given Valproic Acid (VPA) for the next 24 hours. An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Dihydroergotamine | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| OG002 | Cross-Over to Dihydroergotamine | An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Patients who do not respond to VPA after 24 hours will be given Dihydroergotamine (DHE) for the next 24 hours. Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
| OG003 | Cross-Over to Valproic Acid | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Patients who do not respond to DHE after 24 hours will be given Valproic Acid (VPA) for the next 24 hours. An initial dose of Valproic Acid (VPA) will be given IV at 20mg/kg, followed by continuous infusion of 1mg/kg/hour for 24 hours. Serum levels of VPA will be checked at 4 and 24 hours, with additional timepoints possible at 8 and 12 hours based on drug levels. Valproic Acid (VPA): IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg |
|
|
| Secondary | Percentage of Participants With Presence of Photophobia | Presence of absence of photophobia | No participants were enrolled in the cross-over to dihydroergotamine arm. Participants were analyzed on a per-arm basis. Data were not collected for DHE only for the two participants who crossed over to Valproic Acid; only the combination of treatments. | Posted | Number | percentage of participants w/photophobia | Baseline, 4, 8, 12 and 24 hours |
|
|
|
| Secondary | Percentage of Participants With Presence of Phonophobia | Presence of absence of phonophobia | No participants were enrolled in the cross-over to dihydroergotamine arm. Participants were analyzed on a per-arm basis. Data were not collected for DHE only for the two participants who crossed over to Valproic Acid; only the combination of treatments. | Posted | Number | percentage of participants w/phonophobia | Baseline, 4, 8, 12 and 24 hours |
|
|
|
| Secondary | Percentage of Participants With Presence of Nausea | Presence or absence of nausea | No participants were enrolled in the cross-over to dihydroergotamine arm. Participants were analyzed on a per-arm basis. Data were not collected for DHE only for the two participants who crossed over to Valproic Acid; only the combination of treatments. | Posted | Number | percentage of participants w/nausea | Baseline, 4, 8, 12 and 24 hours |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Dihydroergotamine | Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours. Dihydroergotamine (DHE): 0 hour: 0.50 x (wt in kg) x (0.014) =Xmg 8 hour: 0.75 x (wt in kg) x (0.014) =Xmg 24 hour: 1.00 x (wt in kg) x (0.014) =Xmg | 0 | 12 | 0 | 12 | 3 | 12 |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment | Participant experienced dyspnea and anxiety |
|
Not provided
Not provided
Not provided
| D009422 | Nervous System Diseases |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D005232 | Fatty Acids, Volatile |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D004879 | Ergotamines |
| D004876 | Ergot Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Title | Measurements |
|---|---|
|
| 8 hours |
|
| 12 hours |
|
| 24 hours |
|
| Title | Measurements |
|---|---|
|
| 8 hours |
|
| 12 hours |
|
| 24 hours |
|
| Title | Measurements |
|---|---|
|
| 8 hours |
|
| 12 hours |
|
| 24 hours |
|