Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)
Condition: Post Traumatic Stress Disorder (PTSD); Addiction; Alcohol Abuse
MeSH terms: Alcoholism; Stress Disorders, Traumatic; Behavior, Addictive; Alcohol Drinking; Stress Disorders, Post-Traumatic
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): N-Acetylcysteine (NAC) Treatment; Cognitive Behavioral Therapy (CBT); Inactive Placebo Oral Capsule; Functional magnetic resonance imaging (fMRI); Proton magnetic resonance spectroscopy (MRS) Imaging
Intervention type(s): Drug; Behavioral; Drug; Other; Other
Intervention description(s): 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.; Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.; 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.; Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).; Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).
Other intervention name(s): Imaging
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Post Traumatic Stress Disorder (PTSD); Addiction; Alcohol Use Disorder; Cognitive Behavioral Therapy; N-acetylcysteine (NAC)