Post Traumatic Stress DisorderPhase 2NCT03667846
Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With PTSD
A Phase 2 study testing Topiramate in people with Post Traumatic Stress Disorder and Alcohol Use Disorder, run by NYU Langone Health at 1 site in United States.
Trial summary
This is a double-blind, 2-group randomized controlled trial evaluating the effects of topiramate versus placebo in patients with comorbid PTSD and moderate-to-severe AUD. This trial will provide one of the first rigorous tests of whether the effects of topiramate in AUD generalize to patients with co-occurring PTSD… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Post Traumatic Stress Disorder, Alcohol Use Disorder
- What is being tested?
- Topiramate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2019to 31 Aug 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females aged 18-70 years old
- DSM-5 diagnosis of moderate or severe AUD (using SCID5)
- Endorse a desire to cut down or stop drinking
- At least 4 heavy drinking days (4 or more drinks per day for a woman, 5 or more drinks per day for a man) in the 30 days prior to screen
- DSM-5 current diagnosis of PTSD with the Clinician Administered PTSD Scale OR subPTSD diagnosis (meeting criterion A, F, G, H and at least 6 symptoms across any criteria B-E) with Clinician Administered PTSD Scale (CAPS-5)
- If of childbearing potential (male or female), are willing to use contraception for duration of the trial
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- Able to provide at least 2 locators
- Able to provide voluntary informed consent
- Confirms they are reliably domiciled
Who cannot join
- Current alcohol withdrawal (CIWA-Ar score >7)
- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder I, current significant suicidality (assessed using the C-SSRS), any significant suicidal behavior in the past 12 months, or any history of serious suicide attempts requiring hospitalization, or active homicidality
- DSM-5 diagnosis of current severe substance use disorder for a substance other than alcohol or nicotine
- Any history of severe traumatic brain injury (assessed using the OSU TBI-ID modified). If current (past 12 months) mild/moderate TBI and CSI score ≥12 (for either lifetime month or current month), the PI will determine eligibility.
- Exposure to trauma in the last 30 days, including police duty or military service
- Significantly impaired liver function defined as a) alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN); b) ALT or AST > 3 x ULN with concomitant total bilirubin > 2.0 x ULN; or c) ALT or AST ≥ 3 x ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia
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- Other medical conditions which would preclude safe participation in the study
- Significant laboratory abnormalities, including significantly impaired hepatic function, abnormalities in complete blood count or metabolic panel
- Current use of medications with the potential for adverse drug-drug interactions including but not limited to CNS depressants specified anticonvulsants (such as: Phenytoin, Carbamazepine and Depakote), metformin, and pharmacologic treatments for addictions including alcohol use disorder ,and other Carbonic Anhydrase inhibitors (i.e. zonisamide, acetazolamide, dichlorphenamide). Oral contraceptives are permitted as long as participants who are on an estrogen and/or estrogen-progesterone form use a double barrier contraceptive. Antidepressant medications are permitted if participants have been on a stable dose for at least 4 weeks prior to screening and the dose may not be changed during treatment phase (weeks 0-14) of the study.
- Pregnancy or lactation
- Current treatment for AUD (with the exception of AA/12-step treatment and/or psychosocial treatment initiated more than 2 months prior to the screening visit)
- Current treatment for methadone or opioid abuse
- Psychotherapy for PTSD or other psychiatric condition, if initiated within 3 months of screening
- Allergy or hypersensitivity to topiramate
- Active legal problems likely to result in incarceration within 12 weeks of treatment initiation
- Significantly impaired renal function defined as) creatinine clearance rate <70 mL/min/1.73 m2.
- High risk of adverse emotional or behavioral reaction, and/or an inability to understand study procedures or the informed consent process, based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, lack of meaningful social support)
- Inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency Department stays
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
New York University School of Medicine
New York, New York, 10016
Dayeon Cho, 646-754-7454, Dayeon.Cho@nyulangone.org
Charles Marmar, MD
About this study
Official title: Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With Post Traumatic Stress Disorder
This is a double-blind, 2-group randomized controlled trial evaluating the effects of topiramate versus placebo in patients with comorbid PTSD and moderate-to-severe AUD. This trial will provide one of the first rigorous tests of whether the effects of topiramate in AUD generalize to patients with co-occurring PTSD, and one of the first rigorous tests of whether topiramate has beneficial effects on PTSD symptoms in this population. It will be the first study to test whether the rs2832407 genotype predicts clinical response to topiramate for AUD and PTSD in patients with both disorders. Further, it will contribute to the understanding of topiramate's mechanisms of action in the co-morbid AUD/PTSD population, and to the discovery of predictors of treatment response.
Read the detailed description
Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are highly comorbid, and present a clinical challenge for which existing treatments have limited efficacy. Existing clinical evidence suggests treatments that simultaneously address symptoms of both PTSD and AUD should be more efficacious than treating either disorder in isolation. The overlap in the neurobiological basis of PTSD and AUD (involving alterations in incentive salience, stress/negative affect, and executive control network functioning) suggests that there could be treatments that would effectively treat both disorders. However, there is no pharmacotherapy or psychotherapy treatment that is clearly effective for both disorders.
Topiramate, an FDA-approved anticonvulsant with effects on GABAergic and glutamatergic signaling, has demonstrated efficacy in the treatment of AUD in several randomized clinical trials (RCTs), and has also been tested in several open-label and small RCTs for treatment of PTSD with some evidence of effectiveness. Positive results in one open-label trial and one small RCT in patients with co-occurring PTSD and AUD suggest that topiramate may have beneficial effects on symptoms of both PTSD and AUD in this population. Preclinical work also supports the efficacy of topiramate in ameliorating anxiety-like behavior and altered stress response in animal models of stress and chronic alcohol exposure. A recent clinical study demonstrated that the effects of topiramate on alcohol use were moderated by a polymorphism of the GRIK1 gene (coding for the kainate receptor GluK1 subunit), such that significant benefit was found only among rs2832407 C-allele homozygotes.
This trial is designed to contrast acute and persisting effects of topiramate to those of placebo treatment in a sample of 150 participants with comorbid PTSD and moderate to severe AUD, and to evaluate the moderating effect of rs2832407 genotype on medication effects. Drug will be titrated over 8 weeks to a maximum dose of 200 mg and continued for 4 more weeks for a total of 12 weeks of treatment, followed by a 2-week taper. Alcohol and PTSD-related outcomes will be assessed at multiple time points throughout the study. Plasma biomarkers and neuropsychological assessments will be obtained at baseline and at week 12. In support of the overall aims of the center focusing on personalized medicine, the trial will serve as a platform for studies of topiramate's effects on brain chemistry and function as measured by fMRI, and EEG . Data from this clinical trial will also contribute to Overall Center Aims investigating the relationship of plasma biomarkers to neuroimaging markers.
- Being tested
- Topiramate, Placebo
- 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
Also called Topamax
Generic topiramate, FDA-approve for clinical use, will be purchased in 25mg, 50mg, and 100mg strengths, and encapsulated.
PlaceboOther
Placebo tablets will be encapsulated in identical capsules.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
| Topiramate | Experimental | Week 0-1: 25 mg qhs Week 1-2: 25 mg qAM, 25 mg qhs Week 2-3: 25 mg qAM, 50 mg qhs Week 3-4: 50 mg qAM, 50 mg qhs Week 4-5: 50 mg qAM, 75 mg qhs Week 5-6: 75 mg qAM, 75 mg qhs Week 6-7: 75 mg qAM, 100 mg qhs Week 7-8: 100 mg qAM, 100 mg qhs Week 8-10: 100 mg qAM, 100 mg qhs Week 10-12: 100 mg qAM, 100 mg qhs Week 12-14: 2-week taper Receives: Drug: Topiramate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure of Time-line Follow-back (TLFB)
Retrospective estimate of daily alcohol consumption over a time period ranging from 7 days to 24 months prior to initial interview
Measured: Day 1
Percent Day Abstinent from Alcohol
Percentage of day abstinent from alcohol between week 9 and week 12
Measured: Week 9 to Week 12
PCL-5 score
20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items. Each question is measured on a 5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range - 0-80; 80 being more severe) can be obtained by summing the scores for each of the 20 items.
Measured: Week 9 to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2018
- Study start10 Oct 2019
- Primary completion31 Aug 2025 (estimated)
- Study completion31 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Sponsor
- Investigators
- Charles Marmar, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03667846
- Sponsor's protocol ID
- 18-01405
- Other IDs
- P01AA027057
- Status last verified
- Mar 2025
- First submitted
- 22 Aug 2018
- Last updated
- 1 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial, after deidentification.
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With Post Traumatic Stress Disorder
- ClinicalTrials.gov ID
- NCT03667846
- Acronym / sponsor ID
- 18-01405
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 10 Oct 2019 (actual)
- Primary completion
- 31 Aug 2025 (estimated)
- Study completion
- 31 Aug 2025 (estimated)
- First posted
- 12 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, 2-group randomized controlled trial evaluating the effects of topiramate versus placebo in patients with comorbid PTSD and moderate-to-severe AUD. This trial will provide one of the first rigorous tests of whether the effects of topiramate in AUD generalize to patients with co-occurring PTSD, and one of the first rigorous tests of whether topiramate has beneficial effects on PTSD symptoms in this population. It will be the first study to test whether the rs2832407 genotype predicts clinical response to topiramate for AUD and PTSD in patients with both disorders. Further, it will contribute to the understanding of topiramate's mechanisms of action in the co-morbid AUD/PTSD population, and to the discovery of predictors of treatment response.
Detailed description
Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are highly comorbid, and present a clinical challenge for which existing treatments have limited efficacy. Existing clinical evidence suggests treatments that simultaneously address symptoms of both PTSD and AUD should be more efficacious than treating either disorder in isolation. The overlap in the neurobiological basis of PTSD and AUD (involving alterations in incentive salience, stress/negative affect, and executive control network functioning) suggests that there could be treatments that would effectively treat both disorders. However, there is no pharmacotherapy or psychotherapy treatment that is clearly effective for both disorders.
Topiramate, an FDA-approved anticonvulsant with effects on GABAergic and glutamatergic signaling, has demonstrated efficacy in the treatment of AUD in several randomized clinical trials (RCTs), and has also been tested in several open-label and small RCTs for treatment of PTSD with some evidence of effectiveness. Positive results in one open-label trial and one small RCT in patients with co-occurring PTSD and AUD suggest that topiramate may have beneficial effects on symptoms of both PTSD and AUD in this population. Preclinical work also supports the efficacy of topiramate in ameliorating anxiety-like behavior and altered stress response in animal models of stress and chronic alcohol exposure. A recent clinical study demonstrated that the effects of topiramate on alcohol use were moderated by a polymorphism of the GRIK1 gene (coding for the kainate receptor GluK1 subunit), such that significant benefit was found only among rs2832407 C-allele homozygotes.
This trial is designed to contrast acute and persisting effects of topiramate to those of placebo treatment in a sample of 150 participants with comorbid PTSD and moderate to severe AUD, and to evaluate the moderating effect of rs2832407 genotype on medication effects. Drug will be titrated over 8 weeks to a maximum dose of 200 mg and continued for 4 more weeks for a total of 12 weeks of treatment, followed by a 2-week taper. Alcohol and PTSD-related outcomes will be assessed at multiple time points throughout the study. Plasma biomarkers and neuropsychological assessments will be obtained at baseline and at week 12. In support of the overall aims of the center focusing on personalized medicine, the trial will serve as a platform for studies of topiramate's effects on brain chemistry and function as measured by fMRI, and EEG . Data from this clinical trial will also contribute to Overall Center Aims investigating the relationship of plasma biomarkers to neuroimaging markers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
| Topiramate | Experimental | Drug: TopiramateWeek 0-1: 25 mg qhs Week 1-2: 25 mg qAM, 25 mg qhs Week 2-3: 25 mg qAM, 50 mg qhs Week 3-4: 50 mg qAM, 50 mg qhs Week 4-5: 50 mg qAM, 75 mg qhs Week 5-6: 75 mg qAM, 75 mg qhs Week 6-7: 75 mg qAM, 100 mg qhs Week 7-8: 100 mg qAM, 100 mg qhs Week 8-10: 100 mg qAM, 100 mg qhs Week 10-12: 100 mg qAM, 100 mg qhs Week 12-14: 2-week taper |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Males and females aged 18-70 years old
- DSM-5 diagnosis of moderate or severe AUD (using SCID5)
- Endorse a desire to cut down or stop drinking
- At least 4 heavy drinking days (4 or more drinks per day for a woman, 5 or more drinks per day for a man) in the 30 days prior to screen
- DSM-5 current diagnosis of PTSD with the Clinician Administered PTSD Scale OR subPTSD diagnosis (meeting criterion A, F, G, H and at least 6 symptoms across any criteria B-E) with Clinician Administered PTSD Scale (CAPS-5)
Key exclusion criteria (18 listed)
- Current alcohol withdrawal (CIWA-Ar score >7)
- DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder I, current significant suicidality (assessed using the C-SSRS), any significant suicidal behavior in the past 12 months, or any history of serious suicide attempts requiring hospitalization, or active homicidality
- DSM-5 diagnosis of current severe substance use disorder for a substance other than alcohol or nicotine
- Any history of severe traumatic brain injury (assessed using the OSU TBI-ID modified). If current (past 12 months) mild/moderate TBI and CSI score ≥12 (for either lifetime month or current month), the PI will determine eligibility.
- Exposure to trauma in the last 30 days, including police duty or military service
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 |
|---|---|---|
| TopiramateAlso: TopamaxGeneric topiramate, FDA-approve for clinical use, will be purchased in 25mg, 50mg, and 100mg strengths, and encapsulated. | Drug | Topiramate |
| PlaceboPlacebo tablets will be encapsulated in identical capsules. | Other | Placebo |
Primary outcome
Measure of Time-line Follow-back (TLFB)
Time frame: Day 1
Retrospective estimate of daily alcohol consumption over a time period ranging from 7 days to 24 months prior to initial interview
Percent Day Abstinent from Alcohol
Time frame: Week 9 to Week 12
Percentage of day abstinent from alcohol between week 9 and week 12
PCL-5 score
Time frame: Week 9 to Week 12
20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The symptom severity score (range - 0-80) can be obtained by summing the scores for each of the 20 items. Each question is measured on a 5-point Likert (0 = "Not at all" to 4 = "Extremely"). A total symptom severity score (range - 0-80; 80 being more severe) can be obtained by summing the scores for each of the 20 items.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.
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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.
Charles Marmar, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Topiramate in people with Post Traumatic Stress Disorder and Alcohol Use Disorder, run by NYU Langone Health 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 9 inclusion and 18 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: looking for participants now, as of the sponsor's last update on 1 Apr 2025. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dayeon Cho (646-754-7454, Dayeon.Cho@nyulangone.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measure of Time-line Follow-back (TLFB) (time frame: Day 1). The study lists 3 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 1 Apr 2025.