Clinical trial NCT02966873: Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)
Official title: A Randomized Controlled Trial of N-Acetylcysteine for Alcohol Use Disorder and Comorbid Post Traumatic Stress Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Post Traumatic Stress Disorder (PTSD)
Addiction
Alcohol Abuse
Keywords: Post Traumatic Stress Disorder (PTSD)
Addiction
Alcohol Use Disorder
Cognitive Behavioral Therapy
N-acetylcysteine (NAC)
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
name: National Institutes of Health (NIH)
First posted: 2016-11-17
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female; any race or ethnicity; age 18 to 70 years old.
2. Subjects must be able to comprehend English.
3. Meet DSM-5 criteria for current alcohol use disorder (AUD).
4. 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 (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive 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 AUD and PTSD (Brady et al., 2000; Kessler et al., 2005). Subjects may meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for another substance use disorder as long as AUD is the primary substance of choice.
5. 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.
6. Must consent to random assignment to N-acetylcysteine (NAC) or placebo.
7. Must consent to complete all treatment and follow-up visits.

Exclusion Criteria:

1. Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, as the study protocol may be therapeutically insufficient.
2. Subjects with a current eating disorder (bulimia, anorexia nervosa) or with dissociative identity disorder, as they are likely to require specific time-intensive psychotherapy.
3. 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.
4. 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.
5. 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.
6. 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.
7. History of childhood or adult seizures of any cause.

Primary outcomes:
measure: Change in Alcohol Use Severity
timeFrame: From baseline to week 12
measure: Change in Alcohol Craving - Obsessive Subscale
timeFrame: From baseline to week 12
measure: Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated
timeFrame: From baseline to week 12
measure: Change in Post Traumatic Stress Disorder Symptom Severity - Self Report
timeFrame: From baseline to week 12
measure: Change in Alcohol Craving - Compulsive Subscale
timeFrame: From baseline to week 12
measure: Change in Alcohol Use Severity - Percent Days Abstinent
timeFrame: From baseline to week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Charleston
country: United States
facility: The Charleston Center
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Sudie Back, PhD
role: PRINCIPAL_INVESTIGATOR
References: