Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)

NCT ID: NCT02966873

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 182 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-01
• Study Completion Date: 2022-09-19

Brief Summary

This is a randomized controlled Phase II clinical trial designed to evaluate the effects of N-acetylcysteine (NAC) in reducing Alcohol Use Disorder (AUD) severity and Post Traumatic Stress Disorder (PTSD) symptomatology among individuals with current AUD and PTSD.

Detailed Description

The primary objective of the proposed Phase II study is to evaluate the effects of N-acetylcysteine (NAC), in reducing (1) Alcohol Use Disorder (AUD) severity and (2) Post Traumatic Stress Disorder (PTSD) symptomatology among individuals (N=200) with current AUD and PTSD. We will also use functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS) to investigate the neural circuitry and neurochemistry underlying comorbid AUD/PTSD and prognostic indicators of positive treatment response. Secondary objectives are to evaluate the effects of NAC on impairment in associated areas of functioning (e.g., depression, anxiety, sleep, risky behaviors). In order to accomplish this we will (1) employ an intent-to-treat, double-blind, placebo-controlled randomized controlled trial that will consist of 12 weeks of treatment with NAC (2400 mg per day) or placebo medication; (2) examine standardized, repeated dependent measures of clinical outcomes at baseline, week 6, week 12, and 3-, 6-, and 12-month follow-up; and (3) employ advanced neuroimaging methodologies, a laboratory cue paradigm, and collect biologic measures of alcohol consumption. All participants will also undergo weekly individual cognitive behavior therapy sessions (CBT).The following specific aims are proposed:

Specific Aim 1: To determine the efficacy of N-acetylcysteine (NAC), as compared to placebo, in reducing alcohol use severity (i.e., total standard drinks, percent days drinking, abstinence rates) and craving.

Specific Aim 2: To determine the efficacy of N-acetylcysteine (NAC), as compared to placebo, in reducing self-report and clinician-rated PTSD symptomatology.

Specific Aim 3: To use multimodal neuroimaging techniques to investigate the pathophysiology underlying AUD and comorbid PTSD, and prognostic indicators of treatment outcome.

The proposed study will answer critical questions regarding the potential of NAC as an effective pharmacotherapy for AUD and comorbid PTSD, and elucidate possible mechanisms underlying improved outcomes. This study has the particular advantage of building directly on positive preliminary findings by (1) further testing NAC in the treatment of individuals with co-occurring AUD/PTSD using a double-blind, placebo-controlled randomized design; (2) measuring functioning in related areas, such as depression and risky behaviors; (3) employing innovative measurements including neuroimaging and laboratory cue paradigms; and (4) employing a multidisciplinary team of experts who have successfully collaborated in the past and are uniquely qualified to implement this type of investigation. This project is directly responsive to the mission of the National Institute of Alcohol and Alcoholism (NIAAA) and the new AUD/PTSD initiative in that it seeks to evaluate a promising therapeutic agent for the treatment of AUD/PTSD and identify neurobiological mechanisms common to AUD/PTSD as potential treatment targets. The findings from this study have the potential to significantly improve the standard of patient care, advance the comorbidity science in this area, and decrease public health expenditures associated with AUD and comorbid PTSD.

Conditions

Post Traumatic Stress Disorder (PTSD); Addiction; Alcohol Abuse

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

N-Acetylcysteine (NAC) Treatment Group

Participant will receive 12 weeks of Active Treatment NAC (2400 mg) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.

Participant will receive one week of study medication at a time from the study physician or the study coordinator. The study medication provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Group Type: EXPERIMENTAL

N-Acetylcysteine (NAC) Treatment

Intervention Type: DRUG

Participant will receive 12 weeks of Active Treatment NAC (2400 mg) daily. The study medication will be provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Cognitive Behavioral Therapy (CBT)

Intervention Type: BEHAVIORAL

Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.

Functional magnetic resonance imaging (fMRI)

Intervention Type: OTHER

Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).

Proton magnetic resonance spectroscopy (MRS) Imaging

Intervention Type: OTHER

Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).

Placebo Group

Participant will receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.

Participant will receive one week of study medication (placebo) at a time from the study physician or the study coordinator. The study medication (placebo) provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Group Type: PLACEBO_COMPARATOR

Cognitive Behavioral Therapy (CBT)

Intervention Type: BEHAVIORAL

Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.

Inactive Placebo Oral Capsule

Intervention Type: DRUG

Participant will receive 12 weeks of inactive placebo. The study medication will be provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Functional magnetic resonance imaging (fMRI)

Intervention Type: OTHER

Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).

Proton magnetic resonance spectroscopy (MRS) Imaging

Intervention Type: OTHER

Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).

Interventions

N-Acetylcysteine (NAC) Treatment

Participant will receive 12 weeks of Active Treatment NAC (2400 mg) daily. The study medication will be provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Intervention Type: DRUG

Cognitive Behavioral Therapy (CBT)

Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.

Intervention Type: BEHAVIORAL

Inactive Placebo Oral Capsule

Participant will receive 12 weeks of inactive placebo. The study medication will be provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Intervention Type: DRUG

Functional magnetic resonance imaging (fMRI)

Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).

Intervention Type: OTHER

Proton magnetic resonance spectroscopy (MRS) Imaging

Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).

Intervention Type: OTHER

Other Intervention Names

Imaging

Eligibility Criteria

Inclusion Criteria

1. Male or female; any race or ethnicity; age 18 to 70 years old.

2. Subjects must be able to comprehend English.

3. Meet DSM-5 criteria for current alcohol use disorder (AUD).

Exclusion Criteria

5. Subjects taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before treatment initiation. This is because initiation or change of medications during the course of the trial may interfere with interpretation of results.

6. Must consent to random assignment to N-acetylcysteine (NAC) or placebo.

7. Must consent to complete all treatment and follow-up visits.

1. Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, as the study protocol may be therapeutically insufficient.

2. Subjects with a current eating disorder (bulimia, anorexia nervosa) or with dissociative identity disorder, as they are likely to require specific time-intensive psychotherapy.

3. Subjects experiencing significant withdrawal symptoms, as evidence by a score of 10 or above on the Clinical Institute Withdrawal Assessment of Alcohol (CIWA). These subjects will be referred for clinical detoxification and may be re-assessed for study eligibility after medically supervised detoxification has been completed.

4. Individuals considered an immediate suicide risk or who are likely to require hospitalization during the course of the study for suicidality.

Women who are pregnant, nursing or not practicing an effective form of birth control.

5. Evidence of liver failure; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 3 times the upper limit of normal; asthma or any clinically significant medical condition that in the opinion of the investigator would adversely affect safety or study participation.

6. Use of carbamazepine, phenytoin, nitrous oxide, methotrexate, 6 azauridine triacetate, or nitroglycerin within the last 14 days or any other medication felt to have a hazardous interaction if taken with NAC.

7. History of childhood or adult seizures of any cause.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Elizabeth Santa Ana

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sudie Back, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

The Charleston Center

Charleston, South Carolina, United States

Countries

United States

References

Back SE, Gray K, Jarnecke AM, Saraiya TC, Santa Ana EJ, Killeen T, Joseph JE, Prisciandaro JJ, Brown DG, Nietert PJ, Stecker T, Rothbaum A, Jones JL, Flanagan JC, Brady KT. N-Acetylcysteine for the Treatment of Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder: A Double-Blind, Randomized Controlled Trial. J Clin Psychiatry. 2025 Aug 27;86(4):25m15803. doi: 10.4088/JCP.25m15803.

Reference Type: DERIVED

PMID: 40875537 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01AA025086

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00056889

Identifier Type: -

Identifier Source: org_study_id