NCT02966873

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
182

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Oct 2016

Longer than P75 for phase_2

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2016

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

November 4, 2016

Completed
13 days until next milestone

First Posted

Study publicly available on registry

November 17, 2016

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 16, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

September 19, 2022

Completed
7 months until next milestone

Results Posted

Study results publicly available

April 18, 2023

Completed
Last Updated

April 13, 2026

Status Verified

March 1, 2026

Enrollment Period

5 years

First QC Date

November 4, 2016

Results QC Date

December 22, 2022

Last Update Submit

March 23, 2026

Conditions

Keywords

Post Traumatic Stress Disorder (PTSD)AddictionAlcohol Use DisorderCognitive Behavioral TherapyN-acetylcysteine (NAC)

Outcome Measures

Primary Outcomes (6)

  • Change in Alcohol Use Severity

    Change in Alcohol Use Severity as measured by standard drinks per day using the Time Line Follow Back (TLFB) to measure alcohol consumption. Fewer standard drinks per day represent better outcomes. Greater change in standard drinks per day represents better outcomes.

    From baseline to week 12

  • Change in Alcohol Craving - Obsessive Subscale

    Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the obsessive subscale of alcohol craving. The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Obsessive subscale includes items 1-6. Each item is scored on a scale from 0 to 4. Scores range from 0 to 28, with lower scores representing better outcomes.

    From baseline to week 12

  • Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated

    Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered PTSD Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms. The CAPS-5 is a 30-item structured interview. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 PTSD symptoms, each with severity scores ranging from 0-4. The overall total severity score for CAPS-5 ranges from 0-80, with lower scores representing better outcomes (less severe PTSD).

    From baseline to week 12

  • Change in Post Traumatic Stress Disorder Symptom Severity - Self Report

    Change in Post Traumatic Stress Disorder (PTSD) symptom severity as measured by the Posttraumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition \[DSM-5\](PCL-5) for self-reported symptoms. The PCL-5 is a 20-item self-report measure that assesses the 20 symptoms of PTSD. The rating scale is 0-4 for each symptom/item, and overall scores range from 0-80, with lower scores representing better outcomes (less severe PTSD).

    From baseline to week 12

  • Change in Alcohol Craving - Compulsive Subscale

    Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the compulsive subscale of alcohol craving. The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Compulsive subscale includes items 7-14. Each item is scored on a scale from 0 to 4. Scores range from 0 to 32, with lower scores representing better outcomes.

    From baseline to week 12

  • Change in Alcohol Use Severity - Percent Days Abstinent

    Change in Alcohol Use Severity as measured by the percent days abstinent using the Time Line Follow Back (TLFB) to measure alcohol consumption. Greater percentage of days of abstinence represents better outcomes. Greater change in Percent Days Abstinent represents better outcomes.

    From baseline to week 12

Study Arms (2)

N-Acetylcysteine (NAC) Treatment Group

EXPERIMENTAL

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.

Drug: N-Acetylcysteine (NAC) TreatmentBehavioral: Cognitive Behavioral Therapy (CBT)Other: Functional magnetic resonance imaging (fMRI)Other: Proton magnetic resonance spectroscopy (MRS) Imaging

Placebo Group

PLACEBO COMPARATOR

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.

Behavioral: Cognitive Behavioral Therapy (CBT)Drug: Inactive Placebo Oral CapsuleOther: Functional magnetic resonance imaging (fMRI)Other: Proton magnetic resonance spectroscopy (MRS) Imaging

Interventions

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

N-Acetylcysteine (NAC) Treatment GroupPlacebo Group

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.

N-Acetylcysteine (NAC) Treatment Group

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

N-Acetylcysteine (NAC) Treatment GroupPlacebo Group

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.

Placebo Group

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

Also known as: Imaging
N-Acetylcysteine (NAC) Treatment GroupPlacebo Group

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female; any race or ethnicity; age 18 to 70 years old.
  • Subjects must be able to comprehend English.
  • Meet DSM-5 criteria for current alcohol use disorder (AUD).

You may not qualify if:

  • 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.
  • Must consent to random assignment to N-acetylcysteine (NAC) or placebo.
  • Must consent to complete all treatment and follow-up visits.
  • Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, as the study protocol may be therapeutically insufficient.
  • Subjects with a current eating disorder (bulimia, anorexia nervosa) or with dissociative identity disorder, as they are likely to require specific time-intensive psychotherapy.
  • 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.
  • 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.
  • 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.
  • 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.
  • History of childhood or adult seizures of any cause.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Medical University of South Carolina

Charleston, South Carolina, 29401, United States

Location

The Charleston Center

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Stress Disorders, Post-TraumaticBehavior, AddictiveAlcoholism

Interventions

AcetylcysteineTherapeuticsCognitive Behavioral TherapyX-RaysProton Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Stress Disorders, TraumaticTrauma and Stressor Related DisordersMental DisordersCompulsive BehaviorImpulsive BehaviorBehaviorAlcohol-Related DisordersSubstance-Related DisordersChemically-Induced Disorders

Intervention Hierarchy (Ancestors)

CysteineAmino Acids, SulfurSulfur CompoundsOrganic ChemicalsAmino AcidsAmino Acids, Peptides, and ProteinsBehavior TherapyPsychotherapyBehavioral Disciplines and ActivitiesElectromagnetic RadiationElectromagnetic PhenomenaMagnetic PhenomenaPhysical PhenomenaRadiationRadiation, IonizingMagnetic Resonance SpectroscopySpectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Results Point of Contact

Title
Stacey Sellers
Organization
Medical University of South Carolina

Study Officials

  • Sudie Back, PhD

    Medical University of South Carolina

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

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

Study Record Dates

First Submitted

November 4, 2016

First Posted

November 17, 2016

Study Start

October 1, 2016

Primary Completion

September 16, 2021

Study Completion

September 19, 2022

Last Updated

April 13, 2026

Results First Posted

April 18, 2023

Record last verified: 2026-03

Data Sharing

IPD Sharing
Will share

Locations