Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy (TAP)
The proposed project aims to:
- 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;
- Obtain preliminary assessments of safety/tolerability of topiramate in these patients;
- 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 increase in percent days abstinent from baseline to end of treatment.
SECONDARY HYPOTHESIS: There will be a significantly greater percent of days abstinent from alcohol use in the topiramate treatment group compared to the placebo group.
Other: Placebo administration
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy|
- Change in percent days abstinent [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]The primary outcome measure will be the change in percent days abstinent from alcohol use from baseline to end of study, associated with topiramate treatment. This measure will test our primary hypothesis, which is that there will be a significant increase in percent days abstinent from alcohol over successive time periods from baseline to end of treatment in the topiramate treatment group.
- The difference in percent days abstinent from alcohol between the topiramate and placebo arms of the study. [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]The secondary outcome measure will be the difference in percent days abstinent from alcohol use between the topiramate and placebo arms of the study. This outcome will test our secondary hypothesis, which is that there will be a significantly greater percent of days abstinent from alcohol use in the topiramate treatment group compared to the placebo group.
- PTSD symptom severity in veterans with chronic PTSD and alcohol abuse/dependence [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
We will assess changes in PTSD measures (CAPS and PCL) in the topiramate treatment group over successive time periods from baseline to end of treatment. We hypothesize that there will be decreases in the measures of PTSD symptoms.
These PTSD outcome measures will be analyzed in a parallel fashion to the primary outcome, with a separate mixed model for each outcome variable.
|Study Start Date:||April 2010|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||September 2012 (Final data collection date for primary outcome measure)|
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.
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.
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.
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.
|United States, California|
|San Francisco VA Medical Center|
|San Francisco, California, United States, 94121|
|Principal Investigator:||Steven L. Batki, MD||University of California, San Francisco; Department of Veteran's Affairs|