Clinical trial NCT03885154: Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine
Official title: Valproic Acid and Dihydroergotamine as Abortive Therapy in Pediatric Migraine: An Open-Label Randomized Trial.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Migraine in Children
Keywords: Migraine
Headache
Valproic acid
Dihydroergotamine
Pediatric
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2019-03-21
Enrollment: 24
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Pain Perception
timeFrame: Baseline to 24 hours
Secondary outcomes:
measure: Percentage of Participants With Presence of Photophobia
timeFrame: Baseline, 4, 8, 12 and 24 hours
measure: Percentage of Participants With Presence of Phonophobia
timeFrame: Baseline, 4, 8, 12 and 24 hours
measure: Percentage of Participants With Presence of Nausea
timeFrame: Baseline, 4, 8, 12 and 24 hours
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
References: