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
Intervention: N-acetylcysteine; Placebo; Cognitive behavioral therapy
Intervention description: 1200mg bid (2400mg/day); Placebo pills bid; CBT for AUD/SUD, one hour/once a week
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Alcohol; PTSD; Trauma; Veteran; Substance; Drug; Post Traumatic Stress Disorder; Military

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.
    

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).

          -  Meet DSM-5 criteria for current PTSD or subthreshold PTSD. Subjects may also meet
             criteria for a mood disorder (except bipolar affective disorder, see Exclusion
             Criteria) or other anxiety disorders (e.g., panic disorder, agoraphobia, social
             phobia, generalized anxiety disorder). The inclusion of subjects with affective and
             other anxiety disorders is essential because of the marked frequency of the
             co-existence of mood and other anxiety disorders among patients with PTSD (Brady et
             al., 2000; Kessler et al., 2005).

          -  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.

        Exclusion Criteria:

          -  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.

          -  MRI exclusions: Claustrophobia; tattoos above the shoulders; permanent eyeliner or
             permanent artificial eyebrows; cardiac pacemaker; metal fragments in eye, skin, or
             body, including shrapnel; heart valve replacement; brain clips; venous umbrella; being
             a sheet-metal worker or welder; lifetime history of aneurysm surgery; intracranial
             bypass, renal, or aortic clips; prosthetic devices such as middle ear, eye, joint, or
             penile implants; joint replacements; non-removable hearing aid, neurostimulator, or
             insulin pump; shunts/stents; metal mesh/coil implants; metal plate/pin/screws/wires;
             or any other metal implants. Note that individuals who meet inclusion/exclusion
             criteria for the medication component of the study but not the MRI portion (e.g.,
             excluded due to metal implants) will still be eligible to enroll in and complete the
             medication/treatment phase.

          -  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.