Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine

Phase 2

Terminated

Conditions: Migraine in Children

Interventions: Drug: Dihydroergotamine (DHE)
Drug: Valproic Acid (VPA)

Registration Number: NCT03885154

Lead Sponsor: Kimberly S Jones

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

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

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Dihydroergotamine	Dihydroergotamine (DHE)	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	Dihydroergotamine (DHE)	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	Dihydroergotamine (DHE)	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.
Cross-Over to Valproic Acid	Valproic Acid (VPA)	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.
Cross-Over to Dihydroergotamine	Valproic Acid (VPA)	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	Valproic Acid (VPA)	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.

Primary Outcome Measures

Name	Time	Method
Change in Pain Perception	Baseline to 24 hours	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."

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Presence of Nausea	Baseline, 4, 8, 12 and 24 hours	Presence or absence of nausea
Percentage of Participants With Presence of Photophobia	Baseline, 4, 8, 12 and 24 hours	Presence of absence of photophobia
Percentage of Participants With Presence of Phonophobia	Baseline, 4, 8, 12 and 24 hours	Presence of absence of phonophobia