Clinical trial NCT02499029: N-acetylcysteine in the Treatment of PTSD and Addiction
Official title: Glial Regulators for Treating Comorbid Posttraumatic Stress and Substance Abuse Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: PTSD
Addiction
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2015-07-15
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: PTSD Symptoms
timeFrame: 8 weeks
Secondary outcomes:
measure: Depression
timeFrame: 8 weeks
measure: Craving
timeFrame: 8 weeks
measure: PTSD Symptoms
timeFrame: 8 weeks
Other outcomes:
Locations:
Study officials:
References:
citation: Back SE, McCauley JL, Korte KJ, Gros DF, Leavitt V, Gray KM, Hamner MB, DeSantis SM, Malcolm R, Brady KT, Kalivas PW. A Double-Blind, Randomized, Controlled Pilot Trial of N-Acetylcysteine in Veterans With Posttraumatic Stress Disorder and Substance Use Disorders. J Clin Psychiatry. 2016 Nov;77(11):e1439-e1446. doi: 10.4088/JCP.15m10239.