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

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Treatments: Topiramate

Criteria

Inclusion Criteria:

1. Males and females aged 18-70 years old

2. DSM-5 diagnosis of moderate or severe AUD (using SCID5)

3. Endorse a desire to cut down or stop drinking

4. At least 6 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

5. 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)

6. If of childbearing potential (male or female), are willing to use contraception for duration of the trial

7. Able to provide at least 2 locators

8. Able to provide voluntary informed consent

9. Confirms they are reliably domiciled

Exclusion Criteria:

1. Current alcohol withdrawal (CIWA-Ar score >7)

2. DSM-5 diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, 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

3. DSM-5 diagnosis of current moderate or severe substance use disorder for a substance other than alcohol or nicotine

4. 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.

5. Exposure to trauma in the last 30 days, including police duty or military service

6. 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

7. Other medical conditions which would preclude safe participation in the study

8. Significant laboratory abnormalities, including significantly impaired hepatic function, abnormalities in complete blood count or metabolic panel

9. 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.

10. Pregnancy or lactation

11. Current treatment for AUD (with the exception of AA/12-step treatment and/or psychosocial treatment initiated more than 3 months prior to the screening visit)

12. Psychotherapy for PTSD or other psychiatric condition, if initiated within 3 months of screening

13. Allergy or hypersensitivity to topiramate

14. Active legal problems likely to result in incarceration within 12 weeks of treatment initiation

15. Significantly impaired renal function defined as) creatinine clearance rate <70 mL/min/1.73 m2.

16. 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)

17. Inpatient psychiatric treatment in the last 12 months, with the exception of detox and extended Emergency Department stays