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| Sponsor: | Department of Veterans Affairs |
|---|---|
| Collaborators: |
Thomas Jefferson University University of Pittsburgh |
| Information provided by (Responsible Party): | Department of Veterans Affairs |
| ClinicalTrials.gov Identifier: | NCT01122381 |
Purpose
The purpose of this study is to determine whether ethosuximide works better than placebo in the prevention of episodic migraine among veterans.
| Condition | Intervention | Phase |
|---|---|---|
|
Headache, Migraine |
Drug: ethosuximide Other: placebo comparator |
Phase I Phase II |
| Study Type: | Interventional |
| 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 |
| Estimated Enrollment: | 128 |
| 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) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria
|
Drug: ethosuximide
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: 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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Veterans with headache must have migraine categorized using the International Headache Society (I.H.S.) criteria as illustrated below for the two main types with and without aura.
Criteria for migraine without aura (I.H.S. 1.1)
headache with two of the following characteristics
one of the following occurs with headache
Criteria for migraine with aura (I.H.S. 1.2)
at least three of the following characteristics:
One or more fully reversible aura symptoms indicating focal cerebral cortical - and/or brain stem dysfunction.
One or more aura symptoms of the following types:
Headache follows aura with a free interval of less than 60 minutes. (It may also begin before or simultaneously with the aura). Headache, nausea and/or photophobia usually follow neurological aura symptoms directly or after a free interval of less than an hour. The headache usually lasts 4-72 hours, but may be completely absent (1.2.5, acephalgic migraine).
Exclusion Criteria:
7.Significant depression, anxiety, post-traumatic stress disorder, or other disabling psychiatric condition.
8.Known allergies or serious side effects with ESX or succinimides in the past. 9.Known liver or significant renal disease. 10.Women veterans of child-bearing age who do not have adequate birth control. 11.Chronic bone marrow suppression. 12.Using psychogenic or other sedating maintenance drugs. 13.History of porphyria. 14.History of cluster headache. 15.History of other CNS disease. 16.Age younger than 18 years and greater than 65. 17.Women veterans who are breastfeeding. 18. Veterans with familial hemiplegic migraine (FHM).
Ongoing exclusions during the study:
1. The addition of other migraine prophylactic headache med
Contacts and Locations| Contact: Jill S Schaefer, MS | (412) 360-6185 | Jill.Schaefer@VA.gov |
| United States, Pennsylvania | |
| VA Pittsburgh Health Care System | Recruiting |
| Pittsburgh, Pennsylvania, United States, 15240 | |
| Contact: Jill S Schaefer, MS 412-360-6185 Jill.Schaefer@VA.gov | |
| Principal Investigator: Kathy L Gardner, MD | |
| Principal Investigator: | Kathy L Gardner, MD | VA Pittsburgh Health Care System |
More Information
| Responsible Party: | Department of Veterans Affairs |
| ClinicalTrials.gov Identifier: | NCT01122381 History of Changes |
| Other Study ID Numbers: | B5043R |
| Study First Received: | May 10, 2010 |
| Last Updated: | January 5, 2012 |
| Health Authority: | United States: Federal Government; United States: Food and Drug Administration |
|
headache, migraine depression disability evaluation weight gain |
|
Headache Migraine Disorders Pain Neurologic Manifestations Nervous System Diseases Signs and Symptoms Headache Disorders, Primary Headache Disorders |
Brain Diseases Central Nervous System Diseases Ethosuximide Anticonvulsants Central Nervous System Agents Therapeutic Uses Pharmacologic Actions |