NAC for Treating Comorbid PTSD and SUD

NCT ID: NCT02911285

Last Updated: 2021-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2019-11-04

Brief Summary

As a result of sustained operations in Afghanistan and Iraq, there are an increasing number of U.S. military Veterans with substance use disorders and comorbid posttraumatic stress disorder (PTSD). If left untreated, individuals with substance use disorders and PTSD are at increased risk for developing other mental health problems (e.g., depression, anxiety), suicidal ideation and attempts, medical problems, reduced resiliency and military readiness, vocational problems, and family/social impairment. This study will determine the benefits of N-acetylcysteine (NAC) in treating alcohol use disorder and comorbid post-traumatic stress disorder (PTSD) among military Veterans.

Detailed Description

As a result of sustained operations in Afghanistan and Iraq, there are an increasing number of U.S. military Veterans with substance use disorders and comorbid posttraumatic stress disorder (PTSD). While mental health services are in place for U.S. service members, substantial gaps in the treatment of co-occurring substance use disorders and PTSD exist and there is little scientific evidence available to guide the provision of care. Treatment for comorbid substance use disorders and PTSD, especially pharmacologic treatment, is largely ineffective and short-lived. While there have been numerous studies focused largely on dopaminergic mechanisms of reward, they have not led to the development of adequate treatments for comorbid substance use disorders and PTSD. Animal models demonstrate that (a) acute stress and chronic use of addictive substances reduce the capacity of glia to remove the neurotransmitter glutamate, and (b) this impairment as well as relapse can be prevented or reversed by N-acetylcysteine (NAC). Further, human studies indicate that NAC is associated with reduced craving and substance use. Based on this, the investigators conducted a Proof of Principle (PoP) study which was the first to examine the use of NAC for the treatment of PTSD, with or without comorbid addiction. In this randomized, controlled double-blind pilot study the investigators showed that Veterans with substance use disorders (81.5% alcohol use disorder) and PTSD who were treated with 2400mg NAC for 8 weeks demonstrated significant reduction in PTSD severity and craving. Moreover, reductions in PTSD and substance-related symptomatology were sustained at 1-month follow-up. However, to extend and confirm its clinical utility in the military/Veteran context, it is important to know whether NAC reduces severity of alcohol use disorder (AUD), the most common addiction among Veterans and military service members, and the mechanisms underlying therapeutic response. Based on promising data from the PoP project, the proposed Extend-and-Confirm (EC) study will determine the efficacy of NAC in reducing AUD and comorbid PTSD in Veterans (N=90). Further, new aims include the application of functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) to investigate the pathophysiology of AUD/PTSD, as well as prognostic indicators of treatment outcome. These aims extend the Future Plans proposed in the original PoP study and provide an opportunity for collaboration among clinical and preclinical investigators at the Ralph H. Johnson Veterans Affairs (VA) Medical Center and the Medical University of South Carolina (MUSC) to solve this critical health problem in the military context. In the proposed EC study, the investigators will (1) employ a randomized, double-blind, between-groups experimental design that will consist of 8 weeks of treatment with NAC (2400mg) or placebo medication, and follow-up assessment at 1-, 3-, and 6-months post treatment; (2) use standardized, repeated dependent measures to rigorously assess AUD severity and PTSD symptomatology during treatment and follow-up; (3) collect biologic measures of alcohol use; (4) measure impairment in associated areas of functioning (e.g., depression, sleep, suicidality, risky sexual behaviors, family/social functioning); and (5) employ advanced neuroimaging techniques before and after treatment among a subset of enrolled subjects. This proposal is directly responsive to the missions of the Institute for Translational Neuroscience (ITN), and the US Army/Department of Defense (DoD) in that it seeks to accelerate the development of new, medication-based treatments to mitigate the impact of AUD and comorbid psychological conditions, such as PTSD, in the military/Veteran context. The findings of this study will provide critically needed empirical evidence to help inform practice guidelines and better serve the needs of U.S. service members, Veterans and their families.

Conditions

Posttraumatic Stress Disorder (PTSD); Alcohol Use Disorder (AUD); Substance Use Disorder (SUD)

Study Design

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

Study Groups

NAC/CBT

Participants will receive N-acetylcysteine (NAC) and Cognitive Behavioral Therapy (CBT) for 8 weeks.

Group Type: EXPERIMENTAL

N-acetylcysteine

Intervention Type: DRUG

1200mg bid (2400mg/day)

Cognitive behavioral therapy

Intervention Type: BEHAVIORAL

CBT for AUD/SUD, one hour/once a week

Placebo/CBT

Participants will receive placebo pills and CBT for 8 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo pills bid

Cognitive behavioral therapy

Intervention Type: BEHAVIORAL

CBT for AUD/SUD, one hour/once a week

Interventions

N-acetylcysteine

1200mg bid (2400mg/day)

Intervention Type: DRUG

Placebo

Placebo pills bid

Intervention Type: DRUG

Cognitive behavioral therapy

CBT for AUD/SUD, one hour/once a week

Intervention Type: BEHAVIORAL

Other Intervention Names

NAC; CBT

Eligibility Criteria

Inclusion Criteria

• Male or female, any race or ethnicity, age 18 to 75 years old.
• U.S. military Veteran, including National Guard and Reservists.
• Able to comprehend English.
• Meet Diagnostic and Statistical Manual (DSM-5) criteria for current alcohol use disorder (AUD) and/or substance use disorder (SUD).

Exclusion Criteria

• 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 based on the Columbia Suicide Severity Rating Scale (C-SSRS) or who are likely to require hospitalization during the course of the study.
• Women who are pregnant, nursing or not practicing an effective form of birth control.
• Asthma or any clinically significant medical condition that in the opinion of the investigators 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.
• Subjects on maintenance anxiolytic, antidepressant, or mood stabilizing medications which have been initiated during the past four weeks. If it is determined, based on clinical criteria, that a subject needs to be started on maintenance medications for anxiety, mood or psychotic symptoms during the course of the study, they will be discontinued from the treatment trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United States Department of Defense

FED

Sponsor Role: collaborator

Institute for Translational Neuroscience

UNKNOWN

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sudie Back, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Ralph H Johnson VA Medical Center

Charleston, South Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Pro00052757

Identifier Type: -

Identifier Source: org_study_id