Topiramate and Prolonged Exposure

NCT03176953 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: D2412-R
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

PTSD and Alcohol Use Disorder

Keywords

PTSD; alcohol use disorder; Veterans

Outcome Measures

Primary Outcomes (2)

• CAPS-5 Change

  PTSD symptom diagnostic interview CAPS-5 score range = 0 - 80 Higher scores = more severe PTSD symptoms

  Change from baseline to 16 weeks

• Timeline Followback Interview (TLFB)

  substance use severity score range = 0 - 100% of heavy drinking days higher scores = greater percentage of total days that included heavy drinking

  Change from baseline to 16 weeks

Study Arms (2)

prolonged exposure + topiramate

EXPERIMENTAL

psychotherapy plus active medication

Drug: topiramate; Behavioral: prolonged exposure

prolonged exposure + placebo

ACTIVE COMPARATOR

psychotherapy plus placebo medication

Behavioral: prolonged exposure; Drug: placebo

Interventions

topiramate DRUG

active medication

prolonged exposure + topiramate

prolonged exposure BEHAVIORAL

psychotherapy

prolonged exposure + placebo; prolonged exposure + topiramate

placebo DRUG

non-active medication

prolonged exposure + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veterans of the U.S. military and/or Reserve/National Guard members,
• at least 18 years of age,
• survivors of a psychological trauma meeting DSM-5 criterion A, and are 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 last 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 the study,
• are willing to attend psychotherapy, medication, and assessment sessions,
• trying or planning to try to cut down on or abstain from alcohol,
• 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); barrier method is preferred as topiramate may make birth control less effective,
• Individuals with clinically significant renal disease and/or impaired renal function, as defined by clinically significant elevation of blood urea nitrogen (BUN) or creatinine or an estimated creatinine clearance of \< 60 mL/min, can be included with physician approval, however the dosing schedule and maximum dose will be adjusted in accordance with FDA prescribing guidelines,
• if individual is on another addiction medication, they should be on a stable approved addiction medication dose (at least two weeks before starting study drug) throughout the study,
• are capable of giving informed consent.

You may not qualify if:

• Subjects known to have clinically significant unstable medical or psychiatric conditions, where participation is deemed by investigators and study physicians to be risky, including but not limited to:
• AST and/or ALT \>5 times the upper limit of the normal range and/or an increased serum bilirubin \>2 times the upper limit of normal.
• Seizure disorders
• have been treated with Topiramate for any reason in the past and discontinued the drug due to hypersensitivity reaction
• 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., certain types of glaucoma),
• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of California, San Diego: collaborator

Study Sites (1)

VA San Diego Healthcare System, San Diego, CA

San Diego, California, 92161-0002, United States

Location

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Alcoholism

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Sonya Norman, PhD
• Organization: National Center for PTSD

sonya.norman@va.gov

858-518-8266

Study Officials

• Sonya B. Norman, PhD

  VA San Diego Healthcare System, San Diego, CA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind study. Only pharmacist will have access to randomization table.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Participants randomly assigned to one of two conditions.

Study Record Dates

• First Submitted: May 30, 2017
• First Posted: June 6, 2017
• Study Start: November 1, 2017
• Primary Completion: October 31, 2022
• Study Completion: September 30, 2023
• Last Updated: November 18, 2023
• Results First Posted: November 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)