Trial Outcomes & Findings for Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy (NCT NCT01087736)

Last Updated: 2014-06-03

Results Overview

Alcohol consumption was assessed at baseline and weekly during the treatment phase (12 weeks) using the Time Line Follow Back (TLFB) interview which yields number of days of alcohol use (DD). DD: day on which alcohol was consumed Standard alcoholic drink defined as containing 13.6 g of pure alcohol.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

30 participants

Primary outcome timeframe

Weekly, weeks 1-12, average

Results posted on

2014-06-03

Participant Flow

Participant milestones

Participant milestones
Measure	Topiramate Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Overall Study STARTED	14	16
Overall Study COMPLETED	13	14
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Topiramate Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Overall Study Lost to Follow-up	1	0
Overall Study Death	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Topiramate n=14 Participants Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo n=16 Participants Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.	Total n=30 Participants Total of all reporting groups
Age, Continuous	49.5 years STANDARD_DEVIATION 13.9 • n=99 Participants	50.4 years STANDARD_DEVIATION 12.8 • n=107 Participants	50 years STANDARD_DEVIATION 13.1 • n=206 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Sex: Female, Male Male	13 Participants n=99 Participants	15 Participants n=107 Participants	28 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Black or African American	2 Participants n=99 Participants	5 Participants n=107 Participants	7 Participants n=206 Participants
Race (NIH/OMB) White	8 Participants n=99 Participants	8 Participants n=107 Participants	16 Participants n=206 Participants
Race (NIH/OMB) More than one race	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	14 participants n=99 Participants	16 participants n=107 Participants	30 participants n=206 Participants
History of combat exposure Combat exposure	10 participants n=99 Participants	12 participants n=107 Participants	22 participants n=206 Participants
History of combat exposure No combat exposure	4 participants n=99 Participants	4 participants n=107 Participants	8 participants n=206 Participants
Comorbid substance use disorder Comorbid substance use disorder present	5 participants n=99 Participants	5 participants n=107 Participants	10 participants n=206 Participants
Comorbid substance use disorder Comorbid substance use disorder absent	9 participants n=99 Participants	11 participants n=107 Participants	20 participants n=206 Participants
Prior treatment for substance use disorder Residential treatment	4 participants n=99 Participants	2 participants n=107 Participants	6 participants n=206 Participants
Prior treatment for substance use disorder Outpatient treatment	7 participants n=99 Participants	8 participants n=107 Participants	15 participants n=206 Participants
Prior treatment for substance use disorder No prior substance use disorder treatment	3 participants n=99 Participants	6 participants n=107 Participants	9 participants n=206 Participants
BDI	23.4 units on a scale STANDARD_DEVIATION 11.6 • n=99 Participants	26.3 units on a scale STANDARD_DEVIATION 12.3 • n=107 Participants	24.9 units on a scale STANDARD_DEVIATION 11.9 • n=206 Participants
BAI	20.4 units on a scale STANDARD_DEVIATION 12.7 • n=99 Participants	27.4 units on a scale STANDARD_DEVIATION 13.3 • n=107 Participants	24.0 units on a scale STANDARD_DEVIATION 13.3 • n=206 Participants
Alcohol Use Disorders Identification Test	27.1 units on a scale STANDARD_DEVIATION 7.9 • n=99 Participants	23.0 units on a scale STANDARD_DEVIATION 7.5 • n=107 Participants	24.9 units on a scale STANDARD_DEVIATION 7.8 • n=206 Participants
Percent drinking days per week	73.3 percent days in a week STANDARD_DEVIATION 30.3 • n=99 Participants	80.4 percent days in a week STANDARD_DEVIATION 21.5 • n=107 Participants	77.1 percent days in a week STANDARD_DEVIATION 25.8 • n=206 Participants
Percent heavy drinking days per week	58.5 percent days in a week STANDARD_DEVIATION 33.7 • n=99 Participants	72.6 percent days in a week STANDARD_DEVIATION 28.5 • n=107 Participants	66.0 percent days in a week STANDARD_DEVIATION 31.3 • n=206 Participants
Average drinks per week	52.4 Drinks STANDARD_DEVIATION 34.2 • n=99 Participants	58.2 Drinks STANDARD_DEVIATION 25.4 • n=107 Participants	55.5 Drinks STANDARD_DEVIATION 29.4 • n=206 Participants
Average drinks per drinking day	11.1 Drinks STANDARD_DEVIATION 6.1 • n=99 Participants	10.9 Drinks STANDARD_DEVIATION 4.7 • n=107 Participants	11.0 Drinks STANDARD_DEVIATION 5.3 • n=206 Participants
Baseline PTSD Symptomatology PTSD total score	72.8 units on a scale STANDARD_DEVIATION 14.3 • n=99 Participants	83.1 units on a scale STANDARD_DEVIATION 17.3 • n=107 Participants	78.3 units on a scale STANDARD_DEVIATION 16.6 • n=206 Participants
Baseline PTSD Symptomatology Intrusion subscale	18.2 units on a scale STANDARD_DEVIATION 4.3 • n=99 Participants	21.9 units on a scale STANDARD_DEVIATION 6.9 • n=107 Participants	20.2 units on a scale STANDARD_DEVIATION 6.0 • n=206 Participants
Baseline PTSD Symptomatology Avoidance subscale	31.1 units on a scale STANDARD_DEVIATION 6.1 • n=99 Participants	34.8 units on a scale STANDARD_DEVIATION 8.9 • n=107 Participants	33.1 units on a scale STANDARD_DEVIATION 7.8 • n=206 Participants
Baseline PTSD Symptomatology Arousal subscale	23.5 units on a scale STANDARD_DEVIATION 6.7 • n=99 Participants	26.4 units on a scale STANDARD_DEVIATION 4.1 • n=107 Participants	25.0 units on a scale STANDARD_DEVIATION 5.6 • n=206 Participants

PRIMARY outcome

Timeframe: Weekly, weeks 1-12, average

Outcome measures

Outcome measures
Measure	Topiramate n=14 Participants Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo n=16 Participants Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Percent Drinking Days (%DD)	19.5 percent days in a week Standard Deviation 34.2	39.7 percent days in a week Standard Deviation 36.5

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 4, 8, 12

The average PTSD symptom severity score during treatment (weeks 4, 8, 12). The PTSD Checklist (PCL) is a self-report measure of the 17 DSM-IV symptoms of PTSD. Respondents rate on a scale from 1 (not at all) to 5 (extremely) how much they were bothered by each symptom in the past month. A total symptom severity score (range = 17 - 85) can be obtained by summing the scores from the 17 items, with higher scores indicating greater severity of PTSD symptoms. Mean scores may be calculated for subscales of intrusion (range 5-25), avoidance (range 7-35), and arousal (range 5-25).

Outcome measures

Outcome measures
Measure	Topiramate n=14 Participants Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo n=16 Participants Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
PTSD Symptom Severity PCL Total Score (Weeks 1-12 Average)	42.3 units on a scale Standard Deviation 16.4	49.0 units on a scale Standard Deviation 16.5
PTSD Symptom Severity PCL-B Intrusion (Weeks 1-12 Average)	12.3 units on a scale Standard Deviation 5.5	14.3 units on a scale Standard Deviation 5.5
PTSD Symptom Severity PCL-C Avoidance (Weeks 1-12 Average)	17.6 units on a scale Standard Deviation 7.4	19.9 units on a scale Standard Deviation 6.9
PTSD Symptom Severity PCL-D Arousal (Weeks 1-12 Average)	12.4 units on a scale Standard Deviation 4.9	14.9 units on a scale Standard Deviation 5.0

Adverse Events

Topiramate

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Topiramate n=14 participants at risk Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo n=16 participants at risk Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Psychiatric disorders Suicidal ideation	0.00% 0/14 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
Cardiac disorders Chest pain	0.00% 0/14 • 12 Weeks	12.5% 2/16 • Number of events 4 • 12 Weeks
General disorders Death	0.00% 0/14 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks

Other adverse events

Other adverse events
Measure	Topiramate n=14 participants at risk Topiramate: topiramate titrated up over 5 weeks, beginning at 25 mg per day, and increased in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Upon completing the 6 week maintenance period dosage was tapered off over a 7-day period (Week 12).	Placebo n=16 participants at risk Placebo: Placebo pills prepared by the UCSF pharmacy were indistinguishable from the topiramate pills used in that arm. The dosing of placebo pills followed the same regimen as outlined for the topiramate arm. In the event of a safety issue, there would be a procedure for unblinding only that participant.
Nervous system disorders numbness/tingling	21.4% 3/14 • Number of events 3 • 12 Weeks	12.5% 2/16 • Number of events 2 • 12 Weeks
Nervous system disorders Altered taste	21.4% 3/14 • Number of events 3 • 12 Weeks	31.2% 5/16 • Number of events 5 • 12 Weeks
Nervous system disorders Difficulty with concentration/attention	14.3% 2/14 • Number of events 2 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
Nervous system disorders Difficulty with memory	7.1% 1/14 • Number of events 1 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
Nervous system disorders Slow thinking	14.3% 2/14 • Number of events 2 • 12 Weeks	12.5% 2/16 • Number of events 2 • 12 Weeks
Nervous system disorders Confusion	14.3% 2/14 • Number of events 2 • 12 Weeks	18.8% 3/16 • Number of events 3 • 12 Weeks
Nervous system disorders Language problems	7.1% 1/14 • Number of events 1 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
General disorders Fatigue	21.4% 3/14 • Number of events 3 • 12 Weeks	12.5% 2/16 • Number of events 2 • 12 Weeks
General disorders Loss of appetite	28.6% 4/14 • Number of events 4 • 12 Weeks	37.5% 6/16 • Number of events 6 • 12 Weeks
General disorders Dizziness	7.1% 1/14 • Number of events 1 • 12 Weeks	25.0% 4/16 • Number of events 4 • 12 Weeks
General disorders Itching	21.4% 3/14 • Number of events 3 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
General disorders Sleepiness	35.7% 5/14 • Number of events 5 • 12 Weeks	12.5% 2/16 • Number of events 2 • 12 Weeks
Psychiatric disorders Nervousness	7.1% 1/14 • Number of events 1 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
Psychiatric disorders Depression	0.00% 0/14 • 12 Weeks	6.2% 1/16 • Number of events 1 • 12 Weeks
Gastrointestinal disorders Diarrhea	28.6% 4/14 • Number of events 4 • 12 Weeks	18.8% 3/16 • Number of events 3 • 12 Weeks
Eye disorders Abnormal vision	21.4% 3/14 • Number of events 3 • 12 Weeks	18.8% 3/16 • Number of events 3 • 12 Weeks
Eye disorders Eye pain	7.1% 1/14 • Number of events 1 • 12 Weeks	12.5% 2/16 • Number of events 2 • 12 Weeks

Additional Information

David L. Pennington, PhD (Research Psychologist II)

University of California, San Francisco

Phone: 415-221-4810

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place