Trial Outcomes & Findings for Topiramate Treatment of Problem Drinkers (NCT NCT00626925)

Last Updated: 2018-03-08

Results Overview

Change in the number of heavy drinking days during treatment phase of study. Drinking data were aggregated to the weekly level. The number of days per week of heavy drinking (i.e., four or more drinks in a day for women and five or more drinks in a day for men) and of abstinence were the primary outcomes.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

200 participants

Primary outcome timeframe

12 weeks (from initiation to end of treatment)

Results posted on

2018-03-08

Participant Flow

The study was initiated at the University of Connecticut Health Center in March 2008 and was transferred to the University of Pennsylvania in December 2010. The last study visit was completed on 11/20/2013. We enrolled a total of 200 subjects, randomizing 138 to study medication. We recruited participants using flyers, newspaper and radio ads.

Participant milestones

Participant milestones
Measure	Active Med topiramate (up to 200 mg orally) topiramate: up to 200mg/day orally (over 12 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)
Overall Study STARTED	67	71
Overall Study COMPLETED	55	62
Overall Study NOT COMPLETED	12	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Med topiramate (up to 200 mg orally) topiramate: up to 200mg/day orally (over 12 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)
Overall Study Lost to Follow-up	1	2
Overall Study relapse	1	0
Overall Study Adverse effect	6	2
Overall Study Lack of Efficacy	1	4
Overall Study Time constraints	3	1

Baseline Characteristics

Topiramate Treatment of Problem Drinkers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total Topiramate Group n=67 Participants topiramate (up to 200 mg orally) topiramate: up to 200mg/day orally (over 12 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Total Placebo Group n=71 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Total n=138 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 9 • n=39 Participants	52.8 years STANDARD_DEVIATION 7.4 • n=41 Participants	51.07 years STANDARD_DEVIATION 8.3 • n=35 Participants
Sex: Female, Male Female	22 Participants n=39 Participants	30 Participants n=41 Participants	52 Participants n=35 Participants
Sex: Female, Male Male	45 Participants n=39 Participants	41 Participants n=41 Participants	86 Participants n=35 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Asian	0 Participants n=39 Participants	1 Participants n=41 Participants	1 Participants n=35 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Black or African American	10 Participants n=39 Participants	4 Participants n=41 Participants	14 Participants n=35 Participants
Race (NIH/OMB) White	56 Participants n=39 Participants	66 Participants n=41 Participants	122 Participants n=35 Participants
Race (NIH/OMB) More than one race	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants
Proportion Heavy drinking Days preceding screening visit	.67 Proportion Heavy drinking days STANDARD_DEVIATION .27 • n=39 Participants	.66 Proportion Heavy drinking days STANDARD_DEVIATION .27 • n=41 Participants	.66 Proportion Heavy drinking days STANDARD_DEVIATION .27 • n=35 Participants
Location of enrollment University Of Connecticut	39 participants n=39 Participants	37 participants n=41 Participants	76 participants n=35 Participants
Location of enrollment University of Pennsylvania	28 participants n=39 Participants	34 participants n=41 Participants	62 participants n=35 Participants
Education	15.8 years STANDARD_DEVIATION 2.5 • n=39 Participants	15.3 years STANDARD_DEVIATION 2.5 • n=41 Participants	15.5 years STANDARD_DEVIATION 2.5 • n=35 Participants
Marital Status Married	39 Number of participants n=39 Participants	45 Number of participants n=41 Participants	84 Number of participants n=35 Participants
Marital Status Not married	28 Number of participants n=39 Participants	26 Number of participants n=41 Participants	54 Number of participants n=35 Participants
Annual Income Less than $40,000	6 participants n=39 Participants	9 participants n=41 Participants	15 participants n=35 Participants
Annual Income $40,000-$79,999	14 participants n=39 Participants	15 participants n=41 Participants	29 participants n=35 Participants
Annual Income $80,000 -$119,000	18 participants n=39 Participants	19 participants n=41 Participants	37 participants n=35 Participants
Annual Income $120,000 or more	28 participants n=39 Participants	28 participants n=41 Participants	56 participants n=35 Participants
Annual Income Missing	1 participants n=39 Participants	0 participants n=41 Participants	1 participants n=35 Participants
Beck Depression Inventory score	6.1 units on a scale STANDARD_DEVIATION 4.8 • n=39 Participants	6.8 units on a scale STANDARD_DEVIATION 5.3 • n=41 Participants	6.48 units on a scale STANDARD_DEVIATION 5.07 • n=35 Participants
Proportion of abstinent days	0.13 Proportion of abstinent days STANDARD_DEVIATION 0.16 • n=39 Participants	0.12 Proportion of abstinent days STANDARD_DEVIATION 0.15 • n=41 Participants	0.12 Proportion of abstinent days STANDARD_DEVIATION 0.15 • n=35 Participants
Short Index of Problems	14.9 units on a scale STANDARD_DEVIATION 8.6 • n=39 Participants	15.5 units on a scale STANDARD_DEVIATION 6.7 • n=41 Participants	15.20 units on a scale STANDARD_DEVIATION 7.6 • n=35 Participants
Lifetime major depression (M.D.) Lifetime episode Major Depression	18 # of participants n=39 Participants	22 # of participants n=41 Participants	40 # of participants n=35 Participants
Lifetime major depression (M.D.) No lifetime Major Depression episode	49 # of participants n=39 Participants	49 # of participants n=41 Participants	98 # of participants n=35 Participants
Genotype CC	23 Participants n=39 Participants	31 Participants n=41 Participants	54 Participants n=35 Participants
Genotype AC	29 Participants n=39 Participants	32 Participants n=41 Participants	61 Participants n=35 Participants
Genotype AA	15 Participants n=39 Participants	8 Participants n=41 Participants	23 Participants n=35 Participants
Mean Daily Alcohol Consumption	5.426 Number of SD Drinks per day STANDARD_DEVIATION 2.019 • n=39 Participants	5.207 Number of SD Drinks per day STANDARD_DEVIATION 1.735 • n=41 Participants	5.314 Number of SD Drinks per day STANDARD_DEVIATION 1.875 • n=35 Participants

PRIMARY outcome

Timeframe: 12 weeks (from initiation to end of treatment)

Population: Intention to treat (ITT)

Outcome measures

Outcome measures
Measure	Active Med n=67 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=71 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 6 months post treatment
Mean Heavy Drinking Days Per Week by Medication Group	1.82 Number of heavy drinking days Standard Error 0.082	2.94 Number of heavy drinking days Standard Error 0.091	—	—	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: Intention to treat (ITT).

Outcome measures

Outcome measures
Measure	Active Med n=67 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=71 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 6 months post treatment
Mean Abstinent Days Per Week by Medication Group	2.00 Mean abstinent days per week Standard Error 0.085	1.36 Mean abstinent days per week Standard Error 0.065	—	—	—	—

SECONDARY outcome

Timeframe: 12 weeks (from initiation to end of treatment); 3- and 6-months post-treatment

Population: Intention to Treat

Outcome measures

Outcome measures
Measure	Active Med n=67 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=71 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group n=60 Participants Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group n=63 Participants Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group n=59 Participants Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group n=59 Participants Mean Standard Drinks Per Day, 6 months post treatment
Mean Daily Alcohol Consumption	2.9859 Standard Drinks per day Standard Deviation 2.01983	3.5523 Standard Drinks per day Standard Deviation 1.59254	2.6129 Standard Drinks per day Standard Deviation 1.84037	2.7560 Standard Drinks per day Standard Deviation 1.92299	2.6448 Standard Drinks per day Standard Deviation 2.00703	2.8377 Standard Drinks per day Standard Deviation 1.96230

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Active Med n=21 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=30 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group n=24 Participants Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group n=29 Participants Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group n=11 Participants Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group n=7 Participants Mean Standard Drinks Per Day, 6 months post treatment
Mean Heavy Drinking Days Per Week by Medication Group and rs2832407 Genotype	1.28 Mean Heavy Drinking Days Per Week Standard Error 0.131	3.49 Mean Heavy Drinking Days Per Week Standard Error 0.141	2.30 Mean Heavy Drinking Days Per Week Standard Error 0.130	2.72 Mean Heavy Drinking Days Per Week Standard Error 0.129	1.8 Mean Heavy Drinking Days Per Week Standard Error 0.163	1.54 Mean Heavy Drinking Days Per Week Standard Error 0.211

SECONDARY outcome

Timeframe: 12 weeks

Population: ITT

Outcome measures

Outcome measures
Measure	Active Med n=21 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=30 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group n=24 Participants Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group n=29 Participants Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group n=11 Participants Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group n=7 Participants Mean Standard Drinks Per Day, 6 months post treatment
Mean Abstinent Days Per Week by Medication Group and rs2832407 Genotype	2.41 Mean Abstinent Days Per Week Standard Error 0.148	1.02 Mean Abstinent Days Per Week Standard Error 0.090	1.51 Mean Abstinent Days Per Week Standard Error 0.119	1.44 Mean Abstinent Days Per Week Standard Error 0.095	2.26 Mean Abstinent Days Per Week Standard Error 0.186	2.49 Mean Abstinent Days Per Week Standard Error 0.227

SECONDARY outcome

Timeframe: 12 weeks (from intiation to end of treatment)

Population: Subject were measured at Baseline and Endpoint.

The Short Inventory of Problems (SIP). The SIP, a 15-item instrument, yields a total score that ranges from 0 to 45, higher score indicating higher levels of drinking problems. The SIP was derived from the Drinker Inventory of Consequences (DrInC), which was developed for use in Project MATCH (Miller and Tonigan 1995). We (Feinn et al. 2003) have found that, like the DrInC, the SIP measures a single factor of alcohol-related problems. Given that it is substantially shorter than the DrInC, we will use the SIP as a measure of alcohol-related consequences.

Outcome measures

Outcome measures
Measure	Active Med n=67 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=71 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 6 months post treatment
Severity of Alcohol-related Problems at End of Treatment	7.0 units on a scale Standard Deviation 7.2	11.1 units on a scale Standard Deviation 7.5	—	—	—	—

SECONDARY outcome

Timeframe: 6 weeks (from initiation to midpoint)

Population: Subjects were measured at midpoint.

Gamma-glutamyl transferase (GGT) is a liver enzyme biochemical measure used to detect liver health and function and alcohol consumption. GGT is a very sensitive measure than can change very quickly compared to other biochemical markers.

Outcome measures

Outcome measures
Measure	Active Med n=59 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=64 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 6 months post treatment
Gamma-glutamyl Transferase (GGT) at Midpoint	37.6 IU/L Standard Deviation 36.7	50.1 IU/L Standard Deviation 64.8	—	—	—	—

SECONDARY outcome

Timeframe: 12 weeks (from initiation to end of treatment)

Population: ITT

Outcome measures

Outcome measures
Measure	Active Med n=58 Participants Topiramate (up to 200 mg orally) Medication: Topiramate (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=63 Participants placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	3 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 3 months post treatment	3 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 3 months post treatment	6 Month Post Treatment Topiramate Group Mean Standard Drinks Per Day, 6 months post treatment	6 Month Post Treatment Placebo Group Mean Standard Drinks Per Day, 6 months post treatment
Gamma-glutamyl Transferase (GGT) at End of Treatment	36.3 IU/L Standard Deviation 40.2	47.9 IU/L Standard Deviation 52.1	—	—	—	—

Adverse Events

Topiramate Group

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Topiramate Group n=67 participants at risk topiramate (up to 200 mg orally) topiramate: up to 200mg/day orally (over 12 weeks during which the dosage is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)	Placebo Group n=71 participants at risk placebo placebo: placebo (12 weeks during which the dosage of study medication is gradually increased up to 200 mg orally and then maintained, and 1 week of medication taper)
General disorders Numbness/Tingling	53.7% 36/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	14.1% 10/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Change in taste	37.3% 25/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	8.5% 6/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Tireness/Sleepiness	26.9% 18/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	22.5% 16/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Difficulty with memory	23.9% 16/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	22.5% 16/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Loss of appetite	23.9% 16/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	2.8% 2/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Headache	22.4% 15/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	19.7% 14/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Diarrehea	20.9% 14/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	14.1% 10/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Weight loss	19.4% 13/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	2.8% 2/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Difficulty Concentrating	17.9% 12/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	5.6% 4/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Dry Mouth	16.4% 11/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	5.6% 4/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.
General disorders Nausea	10.4% 7/67 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.	11.3% 8/71 • Adverse events were reported from the time of enrollment, throughout the 12 week treatment phase and 6 month followup phase of the study.

Additional Information

Henry R. Kranzler, M.D.

University of Pennsylvania Perelman School of Medicine

Phone: 215-386-6662

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place