Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With PTSD

NCT03667846 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 18-01405P01AA027057
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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, 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.

Conditions

Post Traumatic Stress Disorder; Alcohol Use Disorder

Outcome Measures

Primary Outcomes (3)

• 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

  Day 1

• Percent Day Abstinent from Alcohol

  Percentage of day abstinent from alcohol between week 9 and week 12

  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.

  Week 9 to Week 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

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

Drug: Topiramate

Interventions

Topiramate DRUG

Generic topiramate, FDA-approve for clinical use, will be purchased in 25mg, 50mg, and 100mg strengths, and encapsulated.

Also known as: Topamax

Topiramate

Placebo OTHER

Placebo tablets will be encapsulated in identical capsules.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Able to provide at least 2 locators
• Able to provide voluntary informed consent
• Confirms they are reliably domiciled

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

New York University School of Medicine

New York, New York, 10016, United States

RECRUITING

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

Study Officials

• Charles Marmar, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dayeon Cho

CONTACT

646-754-7454; Dayeon.Cho@nyulangone.org

Michael Bogenschutz, MD

CONTACT

(646) 501-4026; Michael.Bogenschutz@nyulangone.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: September 12, 2018
• Study Start: October 10, 2019
• Primary Completion: August 31, 2025
• Study Completion: August 31, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data will be made available within twelve months of database lock or following publication of primary manuscript, whichever occurs first. Data will be available indefinitely.
• Access Criteria: Anyone who wishes to access the data.

Locations

US (1)