Comparison of a Drug and Placebo in the Prevention of Migraine Headaches

• ClinicalTrials.gov Identifier: NCT01122381
• Recruitment Status: Terminated
• First Posted: May 13, 2010
• Results First Posted: August 19, 2015
• Last Update Posted: August 19, 2015
• Sponsor: US Department of Veterans Affairs
• Collaborators: Thomas Jefferson University; University of Pittsburgh
• Information provided by (Responsible Party): VA Office of Research and Development ( US Department of Veterans Affairs )

• 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
• Enrollment: 5

Participant Flow

Recruitment Details	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	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.

Arm/Group Title	Arm 1-drug Treatment	Arm 2-placebo
Arm/Group Description	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	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
Period Title: Overall Study
Started	1	1
Completed	1 [1]	0
Not Completed	0	1
Reason Not Completed
study terminated early	0	1
[1] Subject never took the drug per review of ESX levels after unblinding

Baseline Characteristics

Arm/Group Title		Arm 1	Arm 2	Total
Arm/Group Description		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	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 of all reporting groups
Overall Number of Baseline Participants		1	1	2
Baseline Analysis Population Description		Enrollees who completed baseline period and randomization.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	1 100.0%	1 100.0%	2 100.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	Female	1 100.0%	0 0.0%	1 50.0%
	Male	0 0.0%	1 100.0%	1 50.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	1 100.0%	1 100.0%	2 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	2 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	1 100.0%	1 100.0%	2 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	1 participants	1 participants	2 participants
		1	1	2

Outcome Measures

1. Primary Outcome

Title	Migraine Headache Days Per 4 Week Period Comparing the Last 4 Weeks of Treatment to a 4 Week Pre-treatment Baseline.
Description	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.
Time Frame	4 weeks, end of treatment and pre-treatment baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1-ethosuximide	Arm 2-placebo Comparator
Arm/Group Description:	Study was terminated early-no outcome data available. Only one subject was assigned to study drug arm but did not actually take it according to subsequent review of ESX drug levels.	Study was terminated early-no outcome data available. Only one subject was assigned to study placebo but was dis-enrolled after titration phase due to study termination.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	16 weeks
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Arm 1- Ethosuximide		Arm 2- Placebo Comparator
Arm/Group Description	ethosuximide blinded capsules of 250mg ESX; subject was titrated up to 4 capsules qd		placebo blinded capsules of "250mg"; subject was titrated up to 4 capsules qd
All-Cause Mortality
	Arm 1- Ethosuximide		Arm 2- Placebo Comparator
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Arm 1- Ethosuximide		Arm 2- Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0.00%)		0/1 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm 1- Ethosuximide		Arm 2- Placebo Comparator
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		1/1 (100.00%)
Gastrointestinal disorders
diarrhea † 1 [1]	0/1 (0.00%)	0	1/1 (100.00%)	1
abdominal pain † 1 [1]	1/1 (100.00%)	1	0/1 (0.00%)	0
nausea † 1 [1]	0/1 (0.00%)	0	1/1 (100.00%)	1
General disorders
fatigue † 1 [1]	1/1 (100.00%)	1	1/1 (100.00%)	1
Nervous system disorders
somnolence † 1 [1]	1/1 (100.00%)	1	0/1 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
hiccups † 1 [1]	1/1 (100.00%)	1	1/1 (100.00%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, CTCAE (4.0); [1] grade 1, mild

Limitations and Caveats

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

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
• EMail: kathy.gardner@va.gov

• Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
• ClinicalTrials.gov Identifier: NCT01122381
• Other Study ID Numbers: B5043-R
• First Submitted: May 10, 2010
• First Posted: May 13, 2010
• Results First Submitted: June 5, 2015
• Results First Posted: August 19, 2015
• Last Update Posted: August 19, 2015