Headache, MigrainePhase 1/2NCT01122381
Comparison of a Drug and Placebo in the Prevention of Migraine Headaches
A Phase 1/2 study testing ethosuximide in people with Headache, Migraine, run by US Department of Veterans Affairs at 1 site in United States.
Trial summary
The purpose of this study is to determine whether ethosuximide works better than placebo in the prevention of episodic migraine among veterans. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Headache, Migraine
- What is being tested?
- ethosuximide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Apr 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be a veteran.
- 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.
- Migraine must have been occurring for 6 months preceding entry into the trial and age of onset should be before age 60 years.
- Migraine must be at least moderate severity and interrupt daily activities in some respect at least 3 times per month.
- 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.
- Migraine diagnosis:
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- 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)
- > 5 attacks
- headache lasting 4-72 hours when untreated or not successfully treated.
- headache with two of the following characteristics
- unilateral,
- pulsating,
- moderate to severe intensity,
- aggravation by exertion.
- one of the following occurs with headache
- nausea and/or vomiting
- photophobia and phonophobia
- Criteria for migraine with aura (I.H.S. 1.2)
- at least 2 attacks
- 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:
- Homonymous visual disturbance
- Unilateral parenthesis and/or numbness
- Unilateral weakness
- Aphasia or unclassifiable speech difficulty
- At least one aura symptom develops gradually over more than 4 minutes or, 2 or more symptoms occur in succession.
- No aura symptom lasts more than 60 minutes. If more than one aura symptom is present, accepted duration is proportionally increased.
- 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).
Who cannot join
- Veterans with migraine plus other systemic disorder will be excluded if migraine onset was temporally related to onset of the systemic disorder.
- 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.
- Use of other prophylactic migraine drugs (requires a washout phase) and cannot have failed more than two other prophylactic drugs for migraine.
- Excessive use of acute pain medicines, including narcotics (>10 days month). Those using non-narcotics could be tapered off over 4-8 weeks.
- Receiving disability or seeking disability for headache or chronic pain.
- Significant neck pain or cervicogenic contributors to chronic headache.
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- Significant depression, anxiety, post-traumatic stress disorder, or other disabling psychiatric condition.
- Known allergies or serious side effects with ESX or succinimides in the past.
- Known liver or significant renal disease.
- Women veterans of child-bearing age who do not have adequate birth control.
- Chronic bone marrow suppression.
- Using psychogenic or other sedating maintenance drugs.
- History of porphyria.
- History of cluster headache. 15.History of other CNS disease.
- Age younger than 18 years and greater than 65.
- Women veterans who are breastfeeding.
- Veterans with familial hemiplegic migraine (FHM).
- Ongoing exclusions during the study:
- The addition of other migraine prophylactic headache medicines is not allowed. 2. New drugs cannot be added that aggravate headache (nitrates, dipyridamole, niacin).
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Pittsburgh Health Care System
Pittsburgh, Pennsylvania, 15240
About this study
Official title: Pharmacologic and Genetic Evaluation of a C. Elegans Model for Migraine
The purpose of this study is to determine whether ethosuximide works better than placebo in the prevention of episodic migraine among veterans.
Read the detailed description
Chronic and episodic headaches in veteran populations include migraine, transformed migraine, and post-traumatic headache with migrainous 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 transforming growth factor-beta (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.
- Conditions
- Headache, Migraine
- Being tested
- ethosuximide, placebo comparator
- Keywords
- headache, migraine, depression, disability evaluation, weight gain
- Medical subject headings
- Migraine Disorders, Depression, Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ethosuximideDrug
Also called zarontin
ethosuximide (ESX)
placebo comparatorOther
placebo
| Study group | Role | What they receive |
|---|---|---|
| Arm 1-ethosuximide | Experimental | ethosuximide blinded capsules of 250mg ESX; titration up to 4 capsules qd (expected) or 5 or 6 capsules for efficacy (not to exceed "30mg"/kg/d) vs maximum tolerability Receives: Drug: ethosuximide |
| Arm 2-placebo comparator | 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 Receives: Other: placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Migraine Headache Days Per 4 Week Period Comparing the Last 4 Weeks of Treatment to a 4 Week Pre-treatment Baseline.
Compare number of migraine headache days pre and post treatment between the ESX and placebo group.
Study terminated early-no outcome data available. The single subject assigned to study drug did not actually take it according to subsequent review of ESX drug levels.
Measured: 4 weeks, end of treatment and pre-treatment baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2010 (estimated)
- Study startDec 2011
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Headache, MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Collaborators
- Thomas Jefferson University, University of Pittsburgh
- Responsible party
- Sponsor
- Investigators
- Kathy L Gardner, MD, Principal investigator, VA Pittsburgh Health Care System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01122381
- Sponsor's protocol ID
- B5043-R
- Status last verified
- Aug 2015
- First submitted
- 10 May 2010
- Last updated
- 19 Aug 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacologic and Genetic Evaluation of a C. Elegans Model for Migraine
- ClinicalTrials.gov ID
- NCT01122381
- Acronym / sponsor ID
- B5043-R
- Conditions
- Headache, Migraine
- Keywords
- headache, migraine, depression, disability evaluation, weight gain
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor recruitment
- Enrolment
- 5 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Collaborators
- Thomas Jefferson University, University of Pittsburgh
- Study start
- Dec 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 13 May 2010 (estimated)
- Results
- Posted 19 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether ethosuximide works better than placebo in the prevention of episodic migraine among veterans.
Detailed description
Chronic and episodic headaches in veteran populations include migraine, transformed migraine, and post-traumatic headache with migrainous 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 transforming growth factor-beta (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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1-ethosuximide | Experimental | Drug: ethosuximideethosuximide blinded capsules of 250mg ESX; titration up to 4 capsules qd (expected) or 5 or 6 capsules for efficacy (not to exceed "30mg"/kg/d) vs maximum tolerability |
| Arm 2-placebo comparator | Placebo comparator | Other: placebo comparatorplacebo 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Must be a veteran.
- 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.
- Migraine must have been occurring for 6 months preceding entry into the trial and age of onset should be before age 60 years.
- Migraine must be at least moderate severity and interrupt daily activities in some respect at least 3 times per month.
- 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.
Key exclusion criteria (19 listed)
- Veterans with migraine plus other systemic disorder will be excluded if migraine onset was temporally related to onset of the systemic disorder.
- 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.
- Use of other prophylactic migraine drugs (requires a washout phase) and cannot have failed more than two other prophylactic drugs for migraine.
- Excessive use of acute pain medicines, including narcotics (>10 days month). Those using non-narcotics could be tapered off over 4-8 weeks.
- Receiving disability or seeking disability for headache or chronic pain.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ethosuximideAlso: zarontinethosuximide (ESX) | Drug | Arm 1-ethosuximide |
| placebo comparatorplacebo | Other | Arm 2-placebo comparator |
Primary outcome
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
Compare number of migraine headache days pre and post treatment between the ESX and placebo group. Study terminated early-no outcome data available. The single subject assigned to study drug did not actually take it according to subsequent review of ESX drug levels.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy L Gardner, MD principal investigator
VA Pittsburgh Health Care System
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ethosuximide in people with Headache, Migraine, run by US Department of Veterans Affairs at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 30 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2015.