N-acetylcysteine in the Treatment of PTSD and Addiction

NCT ID: NCT02499029

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2014-09-30

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.

Conditions

PTSD; Addiction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Identical looking placebo pills were administered each week.

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.

Group Type: EXPERIMENTAL

N-acetylcysteine

Intervention Type: DRUG

NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.

Interventions

N-acetylcysteine

NAC pills were administered each week. NAC is a N acetyl pro-drug of the naturally-occurring amino acid cystine. NAC is a white, crystalline powder with the molecular formula C5H9NO3S and with a molecular weight of 163.2.

Intervention Type: DRUG

Placebo

Identical looking placebo pills were administered each week.

Intervention Type: DRUG

Other Intervention Names

NAC

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: RESULT

PMID: 27736051 (View on PubMed)

Other Identifiers

Pro00021986

Identifier Type: -

Identifier Source: org_study_id