Comparison of a Drug and Placebo in the Prevention of Migraine Headaches - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition:	Headache, Migraine
Interventions:	Drug: ethosuximide Other: placebo comparator

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Primary Care and Neurology Clinic prescreening and recruitment from VA Pittsburgh hospitals during the following periods: 1/14/11-4/1/11; 1/14/12-3/19/12; 2/4/13-3/12/14. Average prescreening of datawarehouse records for eligibility = 2954 subjects/month. Average prescreening electronic chart review for eligibility = 265 subjects/month.

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Primary Care and Neurology Clinic prescreening and recruitment from VA Pittsburgh hospitals during the following periods:

1/14/11-4/1/11; 1/14/12-3/19/12; 2/4/13-3/12/14. Average prescreening of datawarehouse records for eligibility = 2954 subjects/month.

Average prescreening electronic chart review for eligibility = 265 subjects/month.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
5 consented. Initial 4 week baseline period uses headache diary to confirm headache days prior to randomization. 3/5 enrollees did not begin baseline phase; 1 lost to f/u, 1 dis-enrolled due to study interruption, 1 dis-enrolled shortly after consent when another physician began a study excluded drug. 2 enrollees did complete baseline phase.

Reporting Groups

	Description
Arm 1-drug Treatment	migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria 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
Arm 2-placebo	migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria 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

Description

Arm 1-drug Treatment

migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria

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

Arm 2-placebo

migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria

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

Participant Flow: Overall Study

	Arm 1-drug Treatment	Arm 2-placebo
STARTED	1	1
COMPLETED	1 ^[1]	0
NOT COMPLETED	0	1
study terminated early	0	1

^[1]	Subject never took the drug per review of ESX levels after unblinding

Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrollees who completed baseline period and randomization.

Reporting Groups

	Description
Arm 1	migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria 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
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 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
Total	Total of all reporting groups

Description

Arm 1

migraineurs with 4-14 headache days per month that meet all inclusion/exclusion criteria

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

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

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

Total

Total of all reporting groups

Baseline Measures

	Arm 1	Arm 2	Total
Overall Participants Analyzed [Units: Participants]	1	1	2

Age [Units: Participants]
<=18 years	0	0	0
Between 18 and 65 years	1	1	2
>=65 years	0	0	0

Gender [Units: Participants]
Female	1	0	1
Male	0	1	1

Ethnicity (NIH/OMB) [Units: Participants]
Hispanic or Latino	0	0	0
Not Hispanic or Latino	1	1	2
Unknown or Not Reported	0	0	0

Race (NIH/OMB) [Units: Participants]
American Indian or Alaska Native	0	0	0
Asian	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	0	0	0
White	1	1	2
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment [Units: Participants]
United States	1	1	2

Outcome Measures

1. Primary:

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 ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination occurred due to inadequate recruitment of episodic migraineurs in a population meeting too many exclusion criteria; resulting in no subjects available for analysis.

More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact:

Name/Title: Kathy Gardner MD
Organization: Vetarans Administration Pittsburgh Healthcare System
phone: (412) 360-6185
e-mail: kathy.gardner@va.gov

Responsible Party:	VA Office of Research and Development
ClinicalTrials.gov Identifier:	NCT01122381 History of Changes
Other Study ID Numbers:	B5043-R
Study First Received:	May 10, 2010
Results First Received:	June 5, 2015
Last Updated:	August 11, 2015