NAC for Treating Comorbid PTSD and SUD
Condition: Posttraumatic Stress Disorder (PTSD); Alcohol Use Disorder (AUD); Substance Use Disorder (SUD)
MeSH terms: Substance-Related Disorders; Alcoholism; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): N-acetylcysteine; Placebo; Cognitive behavioral therapy
Intervention type(s): Drug; Drug; Behavioral
Intervention description(s): 1200mg bid (2400mg/day); Placebo pills bid; CBT for AUD/SUD, one hour/once a week
Other intervention name(s): NAC; CBT
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Alcohol; PTSD; Trauma; Veteran; Substance; Drug; Post Traumatic Stress Disorder; Military