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)
NCT ID: 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
| 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
| 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
| 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=5 Participants
|
50.4 years
STANDARD_DEVIATION 12.8 • n=7 Participants
|
50 years
STANDARD_DEVIATION 13.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
16 participants
n=7 Participants
|
30 participants
n=5 Participants
|
|
History of combat exposure
Combat exposure
|
10 participants
n=5 Participants
|
12 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
History of combat exposure
No combat exposure
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
8 participants
n=5 Participants
|
|
Comorbid substance use disorder
Comorbid substance use disorder present
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Comorbid substance use disorder
Comorbid substance use disorder absent
|
9 participants
n=5 Participants
|
11 participants
n=7 Participants
|
20 participants
n=5 Participants
|
|
Prior treatment for substance use disorder
Residential treatment
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Prior treatment for substance use disorder
Outpatient treatment
|
7 participants
n=5 Participants
|
8 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Prior treatment for substance use disorder
No prior substance use disorder treatment
|
3 participants
n=5 Participants
|
6 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
BDI
|
23.4 units on a scale
STANDARD_DEVIATION 11.6 • n=5 Participants
|
26.3 units on a scale
STANDARD_DEVIATION 12.3 • n=7 Participants
|
24.9 units on a scale
STANDARD_DEVIATION 11.9 • n=5 Participants
|
|
BAI
|
20.4 units on a scale
STANDARD_DEVIATION 12.7 • n=5 Participants
|
27.4 units on a scale
STANDARD_DEVIATION 13.3 • n=7 Participants
|
24.0 units on a scale
STANDARD_DEVIATION 13.3 • n=5 Participants
|
|
Alcohol Use Disorders Identification Test
|
27.1 units on a scale
STANDARD_DEVIATION 7.9 • n=5 Participants
|
23.0 units on a scale
STANDARD_DEVIATION 7.5 • n=7 Participants
|
24.9 units on a scale
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Percent drinking days per week
|
73.3 percent days in a week
STANDARD_DEVIATION 30.3 • n=5 Participants
|
80.4 percent days in a week
STANDARD_DEVIATION 21.5 • n=7 Participants
|
77.1 percent days in a week
STANDARD_DEVIATION 25.8 • n=5 Participants
|
|
Percent heavy drinking days per week
|
58.5 percent days in a week
STANDARD_DEVIATION 33.7 • n=5 Participants
|
72.6 percent days in a week
STANDARD_DEVIATION 28.5 • n=7 Participants
|
66.0 percent days in a week
STANDARD_DEVIATION 31.3 • n=5 Participants
|
|
Average drinks per week
|
52.4 Drinks
STANDARD_DEVIATION 34.2 • n=5 Participants
|
58.2 Drinks
STANDARD_DEVIATION 25.4 • n=7 Participants
|
55.5 Drinks
STANDARD_DEVIATION 29.4 • n=5 Participants
|
|
Average drinks per drinking day
|
11.1 Drinks
STANDARD_DEVIATION 6.1 • n=5 Participants
|
10.9 Drinks
STANDARD_DEVIATION 4.7 • n=7 Participants
|
11.0 Drinks
STANDARD_DEVIATION 5.3 • n=5 Participants
|
|
Baseline PTSD Symptomatology
PTSD total score
|
72.8 units on a scale
STANDARD_DEVIATION 14.3 • n=5 Participants
|
83.1 units on a scale
STANDARD_DEVIATION 17.3 • n=7 Participants
|
78.3 units on a scale
STANDARD_DEVIATION 16.6 • n=5 Participants
|
|
Baseline PTSD Symptomatology
Intrusion subscale
|
18.2 units on a scale
STANDARD_DEVIATION 4.3 • n=5 Participants
|
21.9 units on a scale
STANDARD_DEVIATION 6.9 • n=7 Participants
|
20.2 units on a scale
STANDARD_DEVIATION 6.0 • n=5 Participants
|
|
Baseline PTSD Symptomatology
Avoidance subscale
|
31.1 units on a scale
STANDARD_DEVIATION 6.1 • n=5 Participants
|
34.8 units on a scale
STANDARD_DEVIATION 8.9 • n=7 Participants
|
33.1 units on a scale
STANDARD_DEVIATION 7.8 • n=5 Participants
|
|
Baseline PTSD Symptomatology
Arousal subscale
|
23.5 units on a scale
STANDARD_DEVIATION 6.7 • n=5 Participants
|
26.4 units on a scale
STANDARD_DEVIATION 4.1 • n=7 Participants
|
25.0 units on a scale
STANDARD_DEVIATION 5.6 • n=5 Participants
|
PRIMARY outcome
Timeframe: Weekly, weeks 1-12, averageAlcohol 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.
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, 12The 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
| 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
| 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
| 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