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Purpose

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.

Condition

Eligibility

Eligible Ages
Between 10 Years and 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • acute migraine as per ICHD-II criteria
  • pediatric (age 10-18)

Exclusion Criteria

For Valproic Acid (VPA)

- Pregnancy

- Liver disease (Acute or Chronic)

- Urea Cycle Disorder

- Mitochondrial Disease

For Dihydroergotamine (DHE)

- Pregnancy

- Peripheral vascular disease, coronary heart disease

- History of cerebrovascular event

- Severe or poorly controlled hypertension

- Impaired liver or renal function

- Triptan given in last 24 hours

- Hemiplegic migraine

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
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.
  • Drug: Valproic Acid (VPA)
    IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours
    Other names:
    • Depakene
Active Comparator
Dihydroergotamine
Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose >1mg and not exceeding 3mg over 24 hours.
  • Drug: 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
Active Comparator
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.
  • Drug: Valproic Acid (VPA)
    IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours
    Other names:
    • Depakene
  • Drug: 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
Active Comparator
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.
  • Drug: Valproic Acid (VPA)
    IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours
    Other names:
    • Depakene
  • Drug: 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

Recruiting Locations

UK Center for Clinical and Translational Science and nearby locations

University of Kentucky
Lexington, Kentucky 40536

More Details

NCT ID
NCT03885154
Status
Recruiting
Sponsor
Kimberly S Jones

Study Contact

Sharoon Qaiser, MBBS
859-218-5011
sharoon.qaiser@uky.edu

Detailed Description

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.

1. Complete Blood Count (CBC)

2. Comprehensive Metabolic Panel (CMP)

3. Prothrombin Time/Activated Partial Thromboplastin Time/International Normalized Ratio (PT/APTT/INR)

4. Magnesium and phosphorous

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.

1. pain (using the standard 0-10 point VAS pain scale)

2. presence or absence of photophobia

3. presence or absence of phonophobia

4. presence or absence of nausea

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.