Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine

Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine: An Open-Label Randomized Trial.

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.

Study Overview

• Status: Terminated
• Conditions: Migraine in Children
• Intervention / Treatment: Drug: Valproic Acid (VPA); Drug: Dihydroergotamine (DHE)

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Kimberly S Jones

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2017
• Primary Completion (Actual): March 19, 2019
• Study Completion (Actual): March 19, 2019

Study Registration Dates

• First Submitted: March 20, 2019
• First Submitted That Met QC Criteria: March 20, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Pediatric; Migraine; Headache; Valproic acid; Dihydroergotamine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agonists; Dopamine Agents; GABA Agents; Anticonvulsants; Antimanic Agents; Vasoconstrictor Agents; Valproic Acid; Dihydroergotamine
• Other Study ID Numbers: 44243

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No