Topiramate and Prolonged Exposure (TOP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03176953
Recruitment Status : Recruiting
First Posted : June 6, 2017
Last Update Posted : September 6, 2018
University of California, San Diego
Information provided by (Responsible Party):
VA Office of Research and Development

Brief Summary:
Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur, and having both disorders is associated with greater psychological and functional impairment than having either disorder alone. The most effective PTSD treatment, prolonged exposure (PE) is sometimes less effective when individuals also have AUD. Anti-relapse medication appears promising to improve the effectiveness of PE to help individuals reduce alcohol use and PTSD symptoms and improve functioning. This study compares PE with and without topiramate, a medication shown to both reduce drinking and PTSD symptoms, with the hypothesis that combined PE and topiramate will be more effective than PE and placebo. The aim of this grant is to improve treatment outcomes for Veterans with AUD and PTSD.

Condition or disease Intervention/treatment Phase
PTSD and Alcohol Use Disorder Drug: topiramate Behavioral: prolonged exposure Drug: placebo Phase 2 Phase 3

Detailed Description:

Objectives. Alcohol use disorder (AUD) and posttraumatic stress disorder (PTSD) frequently co-occur, and having one condition worsens the course of the other. Individuals with both disorders exhibit worse functioning across a number of domains than individuals with either disorder alone. Prolonged exposure therapy (PE) is among the most effective treatments for PTSD. PE has been rated as a frontline treatment by multiple guidelines and reviews including the VA/DoD Clinical Practice Guidelines for the treatment of PTSD. However, in studies of individuals with PTSD and AUD, changes in alcohol use are only slightly better than in control or standard care conditions, reductions in PTSD symptoms are sometimes modest relative to studies of PE in PTSD patients without AUD, and rates of drop out from treatment are high. Combining PE with medication to curb drinking shows promise to improve upon the effectiveness of PE for individuals with comorbid AUD and PTSD, although thus far few studies have examined combining psychotherapy and medication. Topiramate is the single medication that has shown effectiveness for both AUD and PTSD and shows promise for reducing drinking among individuals with AUD and PTSD. However, the effect of adding topiramate to PE to treat comorbid AUD/PTSD has yet to be examined. The critical next step is to test a best practice PTSD treatment, PE, together with a promising pharmacological agent, topiramate, which has been found to be effective for both AUD and PTSD. Innovation: This application seeks to shift current clinical practice paradigms. A refinement to existing interventions is proposed through integration of two evidence based treatments.

Methodology. The investigators propose to use a randomized, controlled, double blind study design to examine the effect of adding topiramate (TOP) to a best practice treatment for PTSD, PE. Participants will be 120 male and female Veterans from all services with AUD and PTSD. The investigators' primary aims are to determine the relative efficacy of PE+topiramate, as compared to PE+placebo, in reducing problematic drinking, reducing PTSD symptoms, and improving functioning and quality of life among Veterans with comorbid AUD/PTSD at post-treatment and 3- and 6-month post-treatment follow-up. The investigators will explore the extent to which decreases in drinking and PTSD symptoms lead to improvement in functioning.

The proposed study has the potential to improve functional and psychological recovery for a highly prevalent and highly impaired population of Veterans. This study will test a novel and innovative combination of psychotherapy and medication with the goal of improving the care of Veterans. The successful completion of this project will help change the practices that drive treatment for Veterans who have both AUD and PTSD. The fundamental rationale for this study is to improve the evidence base that informs how patients with AUD and PTSD can attain sustained recovery from both of these disorders. The investigators will also explore whether changes in PTSD symptoms in the PE+TOP condition are partially explained by reductions in alcohol cravings.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants randomly assigned to one of two conditions.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double blind study. Only pharmacist will have access to randomization table.
Primary Purpose: Treatment
Official Title: Combining Topiramate and Prolonged Exposure for PTSD and Alcohol Use Disorder
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : October 31, 2021
Estimated Study Completion Date : October 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Alcohol
Drug Information available for: Topiramate

Arm Intervention/treatment
Experimental: prolonged exposure + topiramate
psychotherapy plus active medication
Drug: topiramate
active medication

Behavioral: prolonged exposure

Active Comparator: prolonged exposure + placebo
psychotherapy plus placebo medication
Behavioral: prolonged exposure

Drug: placebo
non-active medication

Primary Outcome Measures :
  1. CAPS-5 change [ Time Frame: Change from baseline to 16 weeks ]
    PTSD symptom diagnostic interview

  2. Timeline Followback Interview (TLFB) [ Time Frame: Change from baseline to 16 weeks ]
    substance use severity

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Veteran of the U.S. military or and Reserve/National Guard member
  • are at least 18 years of age
  • have a BMI 18 kg/m2
  • are survivors of a psychological trauma meeting DSM-5 criterion A, at least one month post-trauma
  • have current DSM-5 diagnoses of AUD and PTSD based on semi-structured diagnostic interviews
  • have at least 20 days of heavy drinking (>= 5 drinks/day for men and >= 4/drinks per day for women) in the last 90 days spent in a non-restricted environment and meet criteria for heavy drinking at least 4 days in the 30 days prior to screening
  • are not currently receiving trauma-focused psychotherapy
  • are literate in English and intend to stay in the San Diego area during study participation
  • are willing to attend psychotherapy, medication, and assessment sessions
  • trying or planning to try to cut down on or abstain from alcohol
  • are generally in good health, as confirmed by medical history, physical examination, laboratory tests, and vital signs
  • for females of childbearing potential, agree to use an approved form of contraception for the duration of the study, including:

    • hormonal contraceptives (e.g., oral contraceptives or implantable devices)
    • intrauterine device (IUD)
    • or double barrier methods (e.g., diaphragm with spermicidal condom)
  • are capable of giving informed consent

Exclusion Criteria:

  • based on medical history and physical examination conducted by the study physician, report or show evidence of a clinically significant medical condition including, but not limited to:

    • symptomatic coronary artery or peripheral vascular disease
    • malignancy or history of malignancy within the past 5 years (except basal cell carcinoma)
    • clinically significant renal disease and/or impaired renal function as defined by participants with an estimated creatinine clearance of 60 mL/min
    • clinically significant diseases of the gastrointestinal system including active liver disease
    • participants with AST and/or ALT >3 times the upper limit of the normal range and/or serum bilirubin >2 times the upper limit of normal at screening

      • Note: if these values are abnormal they can be retested prior to enrollment. If the repeat study is within the limits of the protocol, the participant may be randomized
    • pulmonary disorders including participants with active tuberculosis
    • endocrinological disorders
    • neurological disorders including participants with seizure disorders and participants with progressive and degenerative neurological disorders (e.g., multiple sclerosis)
    • any disease or condition that compromises the function of those body systems that could result in altered absorption, excess accumulation or impaired metabolism or excretion of topiramate
    • participants with myocardial infarction, unstable angina, stroke or other major cardiovascular event within 6 months of the screening period
  • have been treated with topiramate for any reason in the past and discontinued the drug due to an adverse event or to a hypersensitivity reaction DSM-5 diagnosis of an uncontrolled psychiatric disorder with psychotic symptoms or cognitive impairment
  • in the opinion of the investigator, should not be enrolled because of the precautions, warnings, or contraindications listed on the topiramate package insert (e.g. history of kidney stones, glaucoma)
  • have a history of nephrolithiasis
  • are taking or plan to take during the study period prohibited medications including, but not limited to

    • other anti-relapse medications
    • stimulants
    • anxiolytics and sedative hypnotics
    • herbal preparations
    • other antiepileptic agents
    • antipsychotics
    • carbonic anhydrase inhibitors
    • systemic corticosteroids
    • or opioid analgesics.

      • These medications will be prohibited for a washout period of five serum half-lives
  • are pregnant, lactating, or plan to become pregnant during the period of participation in the study
  • in the judgment of the investigator, represent a significant risk of suicidal or homicidal behavior

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03176953

Contact: Sonya B Norman, PhD (858) 552-8585 ext 5198
Contact: Erika Blanes, MA (858) 552-8585 ext 6434

United States, California
VA San Diego Healthcare System, San Diego, CA Recruiting
San Diego, California, United States, 92161
Contact: Sonya B Norman, PhD    858-552-8585 ext 5198   
Principal Investigator: Sonya B. Norman, PhD         
Sponsors and Collaborators
VA Office of Research and Development
University of California, San Diego
Principal Investigator: Sonya B. Norman, PhD VA San Diego Healthcare System, San Diego, CA

Responsible Party: VA Office of Research and Development Identifier: NCT03176953     History of Changes
Other Study ID Numbers: D2412-R
First Posted: June 6, 2017    Key Record Dates
Last Update Posted: September 6, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by VA Office of Research and Development:
alcohol use disorder

Additional relevant MeSH terms:
Alcohol Drinking
Drinking Behavior
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents