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

May 1, 2014 updated by: University of California, San Francisco

The proposed project aims to:

  1. Obtain a preliminary assessment of the efficacy of topiramate treatment in reducing alcohol use in veterans with Post Traumatic Stress Disorder (PTSD) and alcohol dependence;
  2. Obtain preliminary assessments of safety/tolerability of topiramate in these patients;
  3. Assess the feasibility of recruitment and retention for topiramate treatment in this comorbid population; and 4) to inform the design of a planned subsequent larger controlled trial of topiramate.

PRIMARY HYPOTHESIS: Topiramate treatment combined with Medical Management alcohol counseling will be associated with a significant decrease in percent drinking days from baseline to end of treatment.

SECONDARY HYPOTHESIS: There will be significantly less percent drinking days in the topiramate treatment group compared to the placebo group.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The goal of the proposed project is to improve the treatment of veterans with co-occurring Post Traumatic Stress Disorder (PTSD) and alcohol dependence. Exposure to the stresses of combat is known to be associated with risk for both PTSD and alcohol and other substance use. PTSD and alcohol use disorders occur frequently among returning OEF/OIF veterans. Alcohol and substance use are risk factors for the development of PTSD, moderators of PTSD symptom severity, and potential consequences of PTSD. Alcohol is by far the most common substance of abuse in patients with PTSD, and its use may represent an attempt by PTSD patients to "self-medicate" symptoms such as hyperarousal. However, to date there has been little research to develop pharmacotherapies that would, ideally, reduce both alcohol use and PTSD symptoms.

Topiramate is one of the few medications for alcohol dependence that has also been tested as a potential medication to treat PTSD. Topiramate's efficacy in alcohol dependence has been shown in two recent large controlled trials. Several open trials have suggested that topiramate may be effective in reducing PTSD symptoms while the results of two small controlled trials have been mixed.

A clinical trial of topiramate is therefore indicated in order to achieve the following specific aims:

The primary aim is to obtain a preliminary assessment of the efficacy of topiramate in increasing the percent of days abstinent from alcohol use from baseline to the end of treatment in veterans with PTSD and alcohol abuse/dependence who are drinking heavily.

The secondary aim is to obtain a preliminary assessment of the efficacy of topiramate in increasing the percent of days abstinent from alcohol as compared to placebo.

Additional aims include the following:

  • To obtain a preliminary assessment of the efficacy of topiramate in reducing other measures of alcohol use such as percent heavy drinking days, number of drinks per week, number of drinks per drinking day, and alcohol craving.
  • To obtain a preliminary assessment of the efficacy of topiramate in reducing PTSD symptom severity in veterans with chronic PTSD and alcohol abuse/dependence.
  • Informing the design of a planned subsequent larger controlled trial of topiramate in veterans with chronic PTSD and alcohol abuse/dependence
  • To obtain an estimate of topiramate vs. placebo effect size for future studies. B. To obtain a preliminary assessment of the effects of topiramate treatment on measures of risk-taking behavior in veterans with chronic PTSD and alcohol abuse/dependence.

To achieve these aims, we will conduct a prospective, parallel groups, randomized, double-blind, placebo-controlled flexible-dose pilot clinical trial of topiramate in veterans with PTSD and alcohol abuse/dependence who are already receiving standard treatment for PTSD but still drink heavily. The primary treatment outcome will be percent days abstinent from alcohol; secondary outcomes will include other alcohol use measures, PTSD symptom severity, adverse effects, recruitment and retention rates.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94121
        • San Francisco VA Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female outpatient veterans.
  • Current DSM-IV diagnosis of PTSD.
  • Current (past month) DSM-IV diagnosis of an Alcohol Use Disorder.
  • Must meet criteria for "heavy" or "at-risk" drinking by NIAAA thresholds.
  • Receiving treatment for PTSD.
  • Must express desire to reduce alcohol consumption.
  • Female subjects must have negative urine pregnancy test and must be either postmenopausal for at least one year, or practicing an effective method of birth control.
  • Must have a BAC of less than 0.02% when signing the informed consent.

Exclusion Criteria:

  • Psychotic disorders, bipolar disorder, dementia, or other psychiatric disorders judged to be unstable.
  • Subjects known to have clinically significant unstable medical conditions, including but not limited to: clinically significant renal disease and/or impaired renal function as defined by clinically significant elevation of BUN or creatinine or an estimated creatinine clearance of < 60 mL/min; AST (SGOT) and/or ALT (SGPT) >3 times the upper limit of the normal range and/or an increased serum bilirubin >2 times the upper limit of normal; seizure disorders.
  • Subjects with glaucoma.
  • Subjects with a history of kidney stones.
  • Subjects with a history of renal disease.
  • Concurrent participation in another treatment study.
  • Female patients who are pregnant or lactating.
  • Current topiramate use or use within the past 4 weeks.
  • Current medications for alcohol dependence or use within the past 4 weeks.
  • Needing acute medical detoxification from alcohol based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD);
  • Subjects who are legally mandated to participate in an alcohol treatment program.
  • Subjects who have had a suicide attempt or suicidal ideation in the 6 months prior to enrollment.
  • Subjects who have previously been treated with topiramate for any reason and discontinued treatment due to an adverse event or due to a hypersensitivity reaction to topiramate,
  • Subjects with seizure disorders that require anticonvulsant medications
  • Subjects currently being treated with another anticonvulsant.
  • Subjects who in the opinion of the investigator should not be enrolled in the study because of the precautions,warnings or contraindications outlined in the topiramate package insert.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Topiramate
Participants will be randomly assigned to either the topiramate arm or placebo arm. Neither the participant nor the researchers will know which arm the participant is in. Participants in the topiramate arm will be ingesting daily doses of topiramate that will gradually increase to a maximum, and then taper off.
Drug: Topiramate
After random assignment, topiramate will be titrated up over 5 weeks. Dosing begins at 25 mg per day, and increase 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. Patients will receive the highest dose tolerated, not to exceed 300 mg per day. Adjustments are permitted throughout titration. Once maximum tolerated dosage is reached, subjects will be asked to maintain dosage for remainder of the treatment phase. Upon completing the 6 week maintenance period subjects will taper off over a 7-day period (Week 12). If subjects experience significant side effects, the dosage may be adjusted.
Other Names:
  • Topamax
  • Qnexa
Placebo Comparator: Placebo
The Drug Product Services Laboratory at UCSF will purchase and supply our lab with USP or NF grade topiramate study capsules and matching placebo capsules. Randomization will be done by a consulting biostatistician, who will be the only one to know which participants are assigned to placebo. Dosing will follow the same procedures as with topiramate in that arm of the study. If adverse events occur, there will be a procedure in place for unblinding only that participant.
Other: Placebo administration
Placebo pills will be prepared by the UCSF pharmacy which will be indistinguishable from the topiramate pills used in that arm. Both topiramate and placebo will then be delivered to the VA pharmacy. A consulting biostatistician will randomly assign participants to either the topiramate or placebo group. The dosing of placebo pills will follow the same regimen as outlined for the topiramate arm. In the event of a safety issue, there will be a procedure for unblinding only that participant.
Other Names:
  • Placebo
  • Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Drinking Days (%DD)
Time Frame: Weekly, weeks 1-12, average

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.
Weekly, weeks 1-12, average

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PTSD Symptom Severity
Time Frame: 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).
Weeks 4, 8, 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

United States Department of Defense
US Department of Veterans Affairs

Investigators

  • Principal Investigator: Steven L. Batki, MD, University of California, San Francisco; Department of Veteran's Affairs

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

September 1, 2012

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

March 15, 2010

First Submitted That Met QC Criteria

March 15, 2010

First Posted (Estimate)

March 16, 2010

Study Record Updates

Last Update Posted (Estimate)

June 3, 2014

Last Update Submitted That Met QC Criteria

May 1, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H5220-34690-01
  • DAMD17-03-1-0532 (Other Grant/Funding Number: Department of Defense)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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