N-acetylcysteine in the Treatment of PTSD and Addiction

Phase 2

Completed

• Conditions: PTSD; Addiction
• Interventions: Drug: N-acetylcysteine; Drug: Placebo

• Registration Number: NCT02499029
• Lead Sponsor: Medical University of South Carolina

Brief Summary

Examine the effects of N-acetylcysteine on PTSD symptoms, craving and substance use in veterans with PTSD and comorbid substance use disorders.

Detailed Description

With the increased number of military veterans returning from conflicts in Afghanistan and Iraq diagnosed with posttraumatic stress disorder (PTSD), there is a high vulnerability of these individuals to develop a substance use disorder (SUD). While there have been a host of studies focused largely on dopaminergic mechanisms of drug reward, they have not led to the development of adequate treatments for either preventing people diagnosed with PTSD from developing SUD or for treating comorbid PTSD/SUD. Based on extensive work with addictive drugs and preliminary data from our group, the investigators propose that stress impairs prefrontal cortex regulation of the basal ganglia habit circuitry and this pathology renders PTSD patients susceptible to developing SUD. Moreover, the known effects of addictive drugs to further impair prefrontal regulation are synergistic with this pathology, thereby making treatment of comorbid PTSD/SUD particularly difficult. Preclinical studies have revealed that glutamate levels within the nucleus accumbens have been implicated in drug seeking behavior in the animal model of relapse. The amino acid precursor N-acetylcysteine (NAC) appears to restore glutamate to normal levels and may also prevent glutamate levels from spiking following subsequent stimulant use. The primary goal of the proposed study is to evaluate the efficacy and safety of N-acetylcysteine in preventing relapse in drug dependent individuals with PTSD or subthreshold PTSD. Veterans with substance use disorders who have achieved at lease one week of abstinence will be randomized to either placebo or NAC (2400-3600mg/day) for 8 weeks.

Study Timeline

• Study Start: 2013-02
• Primary Completion: 2014-09
• Study Completion: 2014-09
• Study First Submitted: 2015-07-01
• Study First Submitted QC: 2015-07-13
• Study First Posted: 2015-07-15
• Results First Submitted: 2017-02-10
• Status Verified: 2018-07
• Results First Submitted QC: 2018-07-31
• Last Update Submitted: 2018-07-31
• Results First Posted: 2018-08-29
• Last Update Posted: 2018-08-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

• 18-65 year old
• U.S. military Veteran, Reservist, or National Guard member
• DSM-IV diagnostic criteria for current (past 6 months) SUD and PTSD or subthreshold PTSD (i.e., met criteria for cluster B (re-experiencing) and either cluster C (avoidance) or D (hyperarousal), as well as duration of one month and clinically significant impairment)
• Score of > 21 on the Mini-Mental State Exam (MMSE).

Exclusion Criteria

• Unstable medical conditions
• Bipolar or psychotic disorders
• Seizures or asthma
• Prior treatment with NAC
• Suicidality
• Enrolled in ongoing PTSD treatment (pharmacotherapy or psychosocial)
• Females: could not be pregnant or lactating

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
N-Acetylcysteine	N-acetylcysteine	Eligible participants were randomized to either NAC (2400 mg/day) or placebo for 8 weeks. The starting dose of NAC was 1200 mg twice daily (2400 mg/day). All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance.
Placebo	Placebo	Identical appearing placebo capsules were dispensed. All NAC and placebo capsules contained riboflavin 25 mg, which was used as a biomarker for medication compliance. Study medications (USP-grade NAC and matched placebo capsules) dispensed to participants by the medical clinician or study staff. Treatment assignment followed a pre-arranged randomization scheme and was carried out by study personnel at the pharmacy (i.e., personnel not involved in clinical management of participants to preserve the double-blind design).

Primary Outcome Measures

Name	Time	Method
PTSD Symptoms	8 weeks	Clinician Administered PTSD Scale IV (CAPS) The CAPS IV measures seventeen symptoms based on intensity and frequency. Intensity and frequency scores are summed to create a severity score for each question. Severity scores are summed to get a total score. A higher total score indicates a higher severity of PTSD symptoms.The full range for CAPS IV is 0-136.

Secondary Outcome Measures

Name	Time	Method
Craving	8 weeks	Visual Analogue Scale (VAS) The VAS measures alcohol craving on a scale from 0 to 10. A higher score indicates a higher level of craving.
Depression	8 weeks	Beck Depression Inventory (BDI) The BDI measures presence and severity of depression. It has 21 questions that are rated from 0-3 with a highest possible score of 63. A higher score indicates a higher severity of depression.
PTSD Symptoms	8 weeks	PTSD Checklist - Military (PCL-M) The PCL-M is a seventeen question self-report, scored on a scale from 1 to 5, with possible scores ranging from 17 to 85. The scores from each question are summed to get a total score (17-85). A higher total indicates a higher severity of PTSD symptoms.