PTSD and Alcohol Use DisorderPhase 2/3TOPNCT03176953
Topiramate and Prolonged Exposure
A Phase 2/3 study testing topiramate and prolonged exposure in people with PTSD and Alcohol Use Disorder, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PTSD and Alcohol Use Disorder
- What is being tested?
- topiramate and prolonged exposure
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2017to 30 Sep 2023
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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,
Show all 13Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
VA San Diego Healthcare System, San Diego, CA
San Diego, California, 92161-0002
About this study
Official title: Combining Topiramate and Prolonged Exposure for PTSD and Alcohol Use Disorder
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.
Read the 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.
- Conditions
- PTSD and Alcohol Use Disorder
- Being tested
- topiramate, prolonged exposure, placebo
- Keywords
- PTSD, alcohol use disorder, Veterans
- Medical subject headings
- Stress Disorders, Post-Traumatic, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
topiramateDrug
active medication
prolonged exposureBehavioural
psychotherapy
placeboDrug
non-active medication
| Study group | Role | What they receive |
|---|---|---|
| prolonged exposure + topiramate | Experimental | psychotherapy plus active medication Receives: Drug: topiramate; Behavioral: prolonged exposure |
| prolonged exposure + placebo | Active comparator | psychotherapy plus placebo medication Receives: Behavioral: prolonged exposure; Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
CAPS-5 Change
PTSD symptom diagnostic interview CAPS-5 score range = 0 - 80 Higher scores = more severe PTSD symptoms
Measured: 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
Measured: Change from baseline to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2017
- Study start1 Nov 2017
- Primary completion31 Oct 2022
- Study completion30 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PTSD and Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants randomly assigned to one of two conditions.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of California, San Diego
- Responsible party
- Sponsor
- Investigators
- Sonya B. Norman, PhD, Principal investigator, VA San Diego Healthcare System, San Diego, CA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03176953
- Sponsor's protocol ID
- D2412-R
- Acronym
- TOP
- Status last verified
- Oct 2023
- First submitted
- 30 May 2017
- Last updated
- 18 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combining Topiramate and Prolonged Exposure for PTSD and Alcohol Use Disorder
- ClinicalTrials.gov ID
- NCT03176953
- Acronym / sponsor ID
- TOP / D2412-R
- Conditions
- PTSD and Alcohol Use Disorder
- Keywords
- PTSD, alcohol use disorder, Veterans
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of California, San Diego
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 30 Sep 2023 (actual)
- First posted
- 6 Jun 2017 (actual)
- Results
- Posted 18 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Participants randomly assigned to one of two conditions.
| Arm | Type | Receives |
|---|---|---|
| prolonged exposure + topiramate | Experimental | Drug: topiramate, Behavioral: prolonged exposurepsychotherapy plus active medication |
| prolonged exposure + placebo | Active comparator | Behavioral: prolonged exposure, Drug: placebopsychotherapy plus placebo medication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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,
Key exclusion criteria (7 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| topiramateactive medication | Drug | prolonged exposure + topiramate |
| prolonged exposurepsychotherapy | Behavioural | prolonged exposure + placebo, prolonged exposure + topiramate |
| placebonon-active medication | Drug | prolonged exposure + placebo |
Primary outcome
CAPS-5 Change
Time frame: Change from baseline to 16 weeks
PTSD symptom diagnostic interview CAPS-5 score range = 0 - 80 Higher scores = more severe PTSD symptoms
Timeline Followback Interview (TLFB)
Time frame: Change from baseline to 16 weeks
substance use severity score range = 0 - 100% of heavy drinking days higher scores = greater percentage of total days that included heavy drinking
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sonya B. Norman, PhD principal investigator
VA San Diego Healthcare System, San Diego, CA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing topiramate and prolonged exposure in people with PTSD and Alcohol Use Disorder, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CAPS-5 Change (time frame: Change from baseline to 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.