Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine

NCT ID: NCT03885154

Last Updated: 2021-10-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-03
• Study Completion Date: 2019-03-19

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.

Conditions

Migraine in Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Valproic Acid (VPA)

Intervention Type: DRUG

IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours

Dihydroergotamine

Dihydroergotamine (DHE) will be given as weight-based dosing, with no single dose \>1mg and not exceeding 3mg over 24 hours.

Group Type: ACTIVE_COMPARATOR

Dihydroergotamine (DHE)

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Valproic Acid (VPA)

Intervention Type: DRUG

IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours

Dihydroergotamine (DHE)

Intervention Type: 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

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.

Group Type: ACTIVE_COMPARATOR

Valproic Acid (VPA)

Intervention Type: DRUG

IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours

Dihydroergotamine (DHE)

Intervention Type: 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

Interventions

Valproic Acid (VPA)

IV VPA load 20mg/kg, followed by continuous infusion of 1mg/kg/hr for 24 hours

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Depakene

Eligibility Criteria

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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kimberly S Jones

OTHER

Sponsor Role: lead

Responsible Party

Kimberly S Jones

Assistant Professor of Neurology and Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University of Kentucky

Lexington, Kentucky, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

44243

Identifier Type: -

Identifier Source: org_study_id