Comparison of a Drug and Placebo in the Prevention of Migraine Headaches
Information source: Department of Veterans Affairs
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Headache, Migraine
Intervention: ethosuximide (Drug); placebo comparator (Other)
Phase: Phase 1/Phase 2
Status: Not yet recruiting
Sponsored by: Department of Veterans Affairs
Official(s) and/or principal investigator(s):
Kathy L Gardner, MD, Principal Investigator, Affiliation: VA Pittsburgh Health Care System
Kathy L Gardner, MD, Phone: (412) 360-6185, Email: firstname.lastname@example.org
The purpose of this study is to determine whether ethosuximide works better than placebo in
the prevention of episodic migraine among veterans.
Official title: Pharmacologic and Genetic Evaluation of a C. Elegans Model for Migraine
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Primary outcome: Migraine headache days per 4 week period comparing the last 4 weeks of treatment to a 4 week pre-treatment baseline.
Determine the percentage with a > 50% reduction and >75% reduction in migraine days last 4 weeks of treatment compared with 4 week baseline
Determine changes in frequency /quantity of acute medication use for migraines during last 4 weeks of treatment compared with 4 week baseline
Determine changes in duration of migraine during last 4 weeks of treatment compared with 4 week baseline
Identify and characterize side effects, especially weight gain compared with baseline 4 week period and placebo response group
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
Compare scoring on the MIDAS migraine disability scale at the end of pretreatment baseline and end of treatment
Compare scoring on the Beck Depression Inventory II at end of treatment with end of pretreatment baseline and to the placebo response group
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
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
Minimum age: 18 Years.
Maximum age: 65 Years.
1. Must be a veteran.
2. The number of migraine days per 4-week period is to be 4-14 for a period of 3 months
prior to screening for entry into the trial.
3. Migraine must have been occurring for 6 months preceding entry into the trial and age
of onset should be before age 60 years.
4. Migraine must be at least moderate severity and interrupt daily activities in some
respect at least 3 times per month.
5. As long as the veteran can easily distinguish nonmigraine headaches from migraine,
there is no limit on the number of non migraine headache days allowed. "Transformed
migraine" headaches due to medication over usage will be excluded according to
exclusion criteria #4.
6. Migraine diagnosis:
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
Criteria for migraine without aura (I. H.S. 1. 1)
1. > 5 attacks
2. headache lasting 4-72 hours when untreated or not successfully treated.
3. headache with two of the following characteristics
3. moderate to severe intensity,
4. aggravation by exertion.
4. one of the following occurs with headache
1. nausea and/or vomiting
2. photophobia and phonophobia
Criteria for migraine with aura (I. H.S. 1. 2)
1. at least 2 attacks
2. at least three of the following characteristics:
1. 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:
1. Homonymous visual disturbance
2. Unilateral parenthesis and/or numbness
3. Unilateral weakness
4. Aphasia or unclassifiable speech difficulty
2. At least one aura symptom develops gradually over more than 4 minutes or, 2 or
more symptoms occur in succession.
3. No aura symptom lasts more than 60 minutes. If more than one aura symptom is
present, accepted duration is proportionally increased.
4. 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).
1. Veterans with migraine plus other systemic disorder will be excluded if
migraine onset was temporally related to onset of the systemic disorder.
2. Blood pressure elevations (must be < borderline values 135/85 for 4 weeks
before enrollment into the study). Current treatment for hypertension with
beta-blockers, calcium channel blockers, or ace inhibitors not allowed.
3. Use of other prophylactic migraine drugs (requires a washout phase) and
cannot have failed more than two other prophylactic drugs for migraine.
4. Excessive use of acute pain medicines, including narcotics (>10 days
month). Those using non-narcotics could be tapered off over 4-8 weeks.
5. Receiving disability or seeking disability for headache or chronic pain.
6. Significant neck pain or cervicogenic contributors to chronic headache.
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
Locations and Contacts
Kathy L Gardner, MD, Phone: (412) 360-6185, Email: email@example.com
VA Pittsburgh Health Care System, Pittsburgh, Pennsylvania 15240, United States
Starting date: June 2010
Last updated: June 14, 2010