Trial Outcomes & Findings for A Randomized, Double-blind Placebo-Controlled Pharmacogenetic Study of Topiramate in European-American Heavy Drinkers (NCT NCT02371889)
NCT ID: NCT02371889
Last Updated: 2022-01-20
Results Overview
The number of Heavy Drinking Days during 12 weeks of treatment in the topiramate and placebo groups.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
320 participants
Primary outcome timeframe
12 weeks
Results posted on
2022-01-20
Participant Flow
The study was conducted from December 18, 2014 through August 1, 2019 at the University of Pennsylvania Treatment Research Center (Penn; n=164) and the Corporal Michael J. Crescenz Veterans Affairs Medical Center (CMCVAMC; n=6).
Participants completed an in-person visit, where they gave informed consent, underwent a medical history, physical examination, routine clinical laboratory testing, a urine drug screen, and, if appropriate, pregnancy testing. We excluded 150 participants based on the first in-person visit based on the inclusion/exclusion criteria from the protocol.
Participant milestones
| Measure |
Topiramate + Medical Management
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|
|
Overall Study
STARTED
|
85
|
85
|
|
Overall Study
COMPLETED
|
66
|
71
|
|
Overall Study
NOT COMPLETED
|
19
|
14
|
Reasons for withdrawal
| Measure |
Topiramate + Medical Management
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|
|
Overall Study
Adverse medication effect
|
11
|
2
|
|
Overall Study
Lost to Follow-up
|
6
|
5
|
|
Overall Study
Personal time constraints
|
2
|
4
|
|
Overall Study
Lack of Efficacy
|
0
|
2
|
|
Overall Study
Relapse
|
0
|
1
|
Baseline Characteristics
A Randomized, Double-blind Placebo-Controlled Pharmacogenetic Study of Topiramate in European-American Heavy Drinkers
Baseline characteristics by cohort
| Measure |
Topiramate + Medical Management
n=85 Participants
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=85 Participants
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Total
n=170 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
|
52.3 years
STANDARD_DEVIATION 10.5 • n=99 Participants
|
50 years
STANDARD_DEVIATION 12.8 • n=107 Participants
|
51.2 years
STANDARD_DEVIATION 11.6 • n=206 Participants
|
|
Sex: Female, Male
Female
|
24 Participants
n=99 Participants
|
25 Participants
n=107 Participants
|
49 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
61 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
121 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
85 Participants
n=99 Participants
|
85 Participants
n=107 Participants
|
170 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 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
|
85 participants
n=99 Participants
|
85 participants
n=107 Participants
|
170 participants
n=206 Participants
|
|
Married or cohabiting
|
47 Participants
n=99 Participants
|
51 Participants
n=107 Participants
|
98 Participants
n=206 Participants
|
|
Genotype
CC genotype
|
30 Participants
n=99 Participants
|
31 Participants
n=107 Participants
|
61 Participants
n=206 Participants
|
|
Genotype
AC/AA genotype
|
55 Participants
n=99 Participants
|
54 Participants
n=107 Participants
|
109 Participants
n=206 Participants
|
|
Lifetime Major Depression
CC genotype
|
7 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Lifetime Major Depression
AC/AA genotype
|
11 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Lifetime Anxiety Disorder
CC genotype
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Lifetime Anxiety Disorder
AC/AA genotype
|
6 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
|
Drinking Days 90days prior to screening
|
87.2 Drinking days
STANDARD_DEVIATION 16.5 • n=99 Participants
|
86.3 Drinking days
STANDARD_DEVIATION 16.8 • n=107 Participants
|
86.5 Drinking days
STANDARD_DEVIATION 17.01 • n=206 Participants
|
|
Heavy drink days 90 days prior to screening
|
73.8 Heavy drinking days
STANDARD_DEVIATION 23.5 • n=99 Participants
|
68.7 Heavy drinking days
STANDARD_DEVIATION 25.6 • n=107 Participants
|
68.9 Heavy drinking days
STANDARD_DEVIATION 26.58 • n=206 Participants
|
PRIMARY outcome
Timeframe: 12 weeksThe number of Heavy Drinking Days during 12 weeks of treatment in the topiramate and placebo groups.
Outcome measures
| Measure |
Topiramate + Medical Management
n=85 Participants
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=85 Participants
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Topiramate + Medical Management
opiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Placebo Pill + Medical Management
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|---|---|
|
Frequency of Heavy Drinking Days by Medication Group (Timeline Follow Back Calendar).
|
29.00 Heavy drinking days
Standard Deviation 23.82
|
41.25 Heavy drinking days
Standard Deviation 26.38
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 weeksNumber of Heavy Drinking Days in the last week of the 12 week treatment phase by medication group and rs2832407 genotype group.
Outcome measures
| Measure |
Topiramate + Medical Management
n=30 Participants
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=31 Participants
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Topiramate + Medical Management
n=55 Participants
opiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Placebo Pill + Medical Management
n=54 Participants
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|---|---|
|
Frequency of Heavy Drinking Days Per Day by Medication and Genotype Group (Timeline Follow Back Calendar).
|
1.86 Heavy drinking days during week 12
Standard Deviation 2.27
|
3.17 Heavy drinking days during week 12
Standard Deviation 2.69
|
2.24 Heavy drinking days during week 12
Standard Deviation 2.46
|
3.14 Heavy drinking days during week 12
Standard Deviation 2.68
|
PRIMARY outcome
Timeframe: 12 weeksNumbers of drinking days over 12 week treatment phase by medication group. Data was collected using timeline follow back calendar.
Outcome measures
| Measure |
Topiramate + Medical Management
n=85 Participants
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=85 Participants
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Topiramate + Medical Management
opiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Placebo Pill + Medical Management
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|---|---|
|
Numbers of Drinking Days Over 12 Weeks Treatment by Medication Group.
|
58.58 Drinking days
Standard Deviation 25.35
|
65.14 Drinking days
Standard Deviation 22.31
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksCumulative number of adverse events as assessed at each study visit to determine the safety of topiramate.
Outcome measures
| Measure |
Topiramate + Medical Management
n=85 Participants
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=85 Participants
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Topiramate + Medical Management
opiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Genotype AA/AC Placebo Pill + Medical Management
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|---|---|
|
Adverse Effects in Study Participants (Questionnaire)
|
3.5 Number of adverse events
Standard Deviation 1.7
|
2.6 Number of adverse events
Standard Deviation 1.3
|
—
|
—
|
Adverse Events
Topiramate + Medical Management
Serious events: 1 serious events
Other events: 80 other events
Deaths: 1 deaths
Placebo Pill + Medical Management
Serious events: 1 serious events
Other events: 76 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Topiramate + Medical Management
n=85 participants at risk
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=85 participants at risk
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
exacerbation of asthma
|
1.2%
1/85 • Number of events 1 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
0.00%
0/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
alcohol-related relapse
|
0.00%
0/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
1.2%
1/85 • Number of events 1 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
Other adverse events
| Measure |
Topiramate + Medical Management
n=85 participants at risk
Topiramate 200 mg/day orally in two divided doses. Dose will be titrated upward over a six-week period, maintained for 6 weeks, then tapered over 6 days + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
Placebo Pill + Medical Management
n=85 participants at risk
Inactive placebo with dosing schedule matched to intervention group + Medical Management sessions for 15-25 minutes per study visit
Medical Management: Medical Management (MM; Pettinati, 2004) will support subjects' efforts to reduce or stop their drinking.
|
|---|---|---|
|
General disorders
Paresthesia
|
54.1%
46/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
10.6%
9/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Headache
|
24.7%
21/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
17.6%
15/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Dysgeusia
|
35.3%
30/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
5.9%
5/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Pain and discomfort
|
18.8%
16/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
20.0%
17/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Fatigue
|
24.7%
21/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
11.8%
10/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Upper respiratory infections
|
24.7%
21/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
11.8%
10/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Eye Disorders
|
20.0%
17/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
8.2%
7/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Speech/Language abnormalities
|
21.2%
18/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
3.5%
3/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Insomnia
|
14.1%
12/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
9.4%
8/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Somnolence
|
14.1%
12/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
7.1%
6/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Diarrhea
|
9.4%
8/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
10.6%
9/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
|
General disorders
Injuries NEC
|
10.6%
9/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
9.4%
8/85 • 12 weeks
Frequency, type, and severity of adverse effects will be assessed at each study visit to determine the safety of topiramate.
|
Additional Information
Henry R. Kranzler, M.D.
University of Pennsylvania Perelman School of Medicine
Phone: 215-746-1943
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place