Comparison of a Drug and Placebo in the Prevention of Migraine Headaches
The purpose of this study is to determine whether ethosuximide works better than placebo in the prevention of episodic migraine among veterans.
Other: placebo comparator
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Pharmacologic and Genetic Evaluation of a C. Elegans Model for Migraine|
- Migraine headache days per 4 week period comparing the last 4 weeks of treatment to a 4 week pre-treatment baseline. [ Time Frame: 4 weeks, end of treatment and pre-treatment baseline ] [ Designated as safety issue: No ]
- Determine the percentage with a > 50% reduction and >75% reduction in migraine days last 4 weeks of treatment compared with 4 week baseline [ Time Frame: last 4 weeks of treatment period ] [ Designated as safety issue: No ]
- Determine changes in frequency /quantity of acute medication use for migraines during last 4 weeks of treatment compared with 4 week baseline [ Time Frame: last 4 weeks of treatment period ] [ Designated as safety issue: No ]
- Determine changes in duration of migraine during last 4 weeks of treatment compared with 4 week baseline [ Time Frame: last 4 weeks of treatment period ] [ Designated as safety issue: No ]
- Identify and characterize side effects, especially weight gain compared with baseline 4 week period and placebo response group [ Time Frame: duration of treatment period for side effects, end of treatment period compared with start of baseline for weight ] [ Designated as safety issue: Yes ]
- Provide CBC, LFT, AED (antiepileptic level) monitoring for possible though unlikely bone marrow or liver toxicity and to ensure drug compliance to be drawn at start, end of study, and with monthly visits [ Time Frame: start of study, every 4 weeks, and end of study ] [ Designated as safety issue: Yes ]
- Compare scoring on the MIDAS migraine disability scale at the end of pretreatment baseline and end of treatment [ Time Frame: end of baseline pre-treatment period to end of treatment period ] [ Designated as safety issue: Yes ]
- Compare scoring on the Beck Depression Inventory II at end of treatment with end of pretreatment baseline and to the placebo response group [ Time Frame: end of pre-treatment baseline to end of treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria
ethosuximide (ESX) 250mg blinded capsules; begin 250mg qd titrating up to 1000mg qd (expected) or 1250mg qd, or 1500mg qd /30mg/kg/d maximum for efficacy goal of < 50% reduction in headache days versus maximum tolerability
Other Name: zarontin
Placebo Comparator: Arm 2
placebo same size blinded capsules as the 250mg ESX; similar titration up to 4 capsules qd (expected) or 5 or 6 capsules for efficacy (not to exceed "30mg"/kg/d) vs maximum tolerability
Other: placebo comparator
placebo same size blinded capsules as the 250mg ESX; similar titration up to 4 capsules qd (expected) or 5 or 6 capsules for efficacy (not to exceed 30mg/kg/d) vs maximum tolerability
Chronic and episodic headaches in veteran populations include migraine, transformed migraine, and post-traumatic headache with migraineous features. More and better prophylactic drugs with fewer side effects (such as weight gain) are needed to treat these disabling, refractory conditions which generally have less than a 50% response rate to preventative treatments.
Rare forms of severe familial hemiplegic migraine (FHM) are considered channelopathies and can be caused by mutations in a calcium channel gene. Serotonin is also known to be a critical neurotransmitter in migraine based on the pharmacology of acute and preventative treatments. We previously identified a "migraine" signaling pathway in an invertebrate C. elegans "hemiplegic migraine" model of a mutant calcium channel upstream from TGF-beta and showed that low serotonin levels can be rescued by treatment with the childhood antiepileptic drug ethosuximide (ESX).
Objective: We propose to test our findings from this invertebrate migraine model to determine its relevance to humans in the prevention of episodic migraine.
Primary Aim: Determine whether ethosuximide (ESX) will be significantly more effective than placebo in reducing migraine headache days. We propose a 3 year, double blind, phase 1/2 randomized, 2:1 ESX:placebo controlled parallel trial in episodic migraineurs comparing migraine headache days during the last 4 weeks of treatment to a pre-treatment 4 week baseline.
|United States, Pennsylvania|
|VA Pittsburgh Health Care System|
|Pittsburgh, Pennsylvania, United States, 15240|
|Principal Investigator:||Kathy L Gardner, MD||VA Pittsburgh Health Care System|