Back to resultsNAC for Treating Comorbid PTSD and SUD (DoD-NAC)
Primary Purpose
Posttraumatic Stress Disorder (PTSD), Alcohol Use Disorder (AUD), Substance Use Disorder (SUD)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
N-acetylcysteine
Placebo
Cognitive behavioral therapy
Sponsored by
About this trial
This is an interventional treatment trial for Posttraumatic Stress Disorder (PTSD) focused on measuring Alcohol, PTSD, Trauma, Veteran, Substance, Drug, Post Traumatic Stress Disorder, Military
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.
Sites / Locations
- Medical University of South Carolina
- Ralph H Johnson VA Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
NAC/CBT
Placebo/CBT
Arm Description
Participants will receive N-acetylcysteine (NAC) and Cognitive Behavioral Therapy (CBT) for 8 weeks.
Participants will receive placebo pills and CBT for 8 weeks.
Outcomes
Primary Outcome Measures
Change in Alcohol Use Disorder Severity
Change in Alcohol Use Disorder Severity as measured by change in average drinking days per week from baseline to week 8.
Greater reduction in drinking days indicates better treatment outcomes. Drinking days measured over 1 week periods (7 days). Scale ranges from 0 days to 7 days.
Change in Post Traumatic Stress Disorder Severity
Change in post traumatic stress disorder severity as measured by Change in Clinician Administered PTSD Scale (CAPS-5) score from baseline to week 8.
Greater change/reduction in score indicates better outcomes and greater reduction in PTSD symptomatology.
(minimum score of 0 = absent to a maximum score of 80 = extreme)
Change in Alcohol Craving
Change in Alcohol craving as measured by change in Obsessive Compulsive Drinking Scale (OCDS) Total Score.
Greater change/reduction in score indicates better outcomes and reduced alcohol craving.
(Scores range from 0 to 56)
Change in Post Traumatic Stress Disorder Severity
Post traumatic stress disorder symptoms as measured by change/reduction in score of post traumatic stress disorder checklist (PCL-5) from baseline to week 8.
Greater reduction in score indicates better treatment outcomes. (minimum score of 0 = absent to a maximum score of 80 = extreme)
Secondary Outcome Measures
Full Information
NCT ID
NCT02911285
First Posted
September 1, 2016
Last Updated
April 28, 2021
Sponsor
Medical University of South Carolina
Collaborators
United States Department of Defense, Institute for Translational Neuroscience
1. Study Identification
Unique Protocol Identification Number
NCT02911285
Brief Title
NAC for Treating Comorbid PTSD and SUD
Acronym
DoD-NAC
Official Title
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and Substance Use Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
October 2016 (Actual)
Primary Completion Date
August 5, 2019 (Actual)
Study Completion Date
November 4, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
Collaborators
United States Department of Defense, Institute for Translational Neuroscience
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed Description
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). While mental health services are in place for U.S. service members, substantial gaps in the treatment of co-occurring substance use disorders and PTSD exist and there is little scientific evidence available to guide the provision of care. Treatment for comorbid substance use disorders and PTSD, especially pharmacologic treatment, is largely ineffective and short-lived. While there have been numerous studies focused largely on dopaminergic mechanisms of reward, they have not led to the development of adequate treatments for comorbid substance use disorders and PTSD. Animal models demonstrate that (a) acute stress and chronic use of addictive substances reduce the capacity of glia to remove the neurotransmitter glutamate, and (b) this impairment as well as relapse can be prevented or reversed by N-acetylcysteine (NAC). Further, human studies indicate that NAC is associated with reduced craving and substance use. Based on this, the investigators conducted a Proof of Principle (PoP) study which was the first to examine the use of NAC for the treatment of PTSD, with or without comorbid addiction. In this randomized, controlled double-blind pilot study the investigators showed that Veterans with substance use disorders (81.5% alcohol use disorder) and PTSD who were treated with 2400mg NAC for 8 weeks demonstrated significant reduction in PTSD severity and craving. Moreover, reductions in PTSD and substance-related symptomatology were sustained at 1-month follow-up. However, to extend and confirm its clinical utility in the military/Veteran context, it is important to know whether NAC reduces severity of alcohol use disorder (AUD), the most common addiction among Veterans and military service members, and the mechanisms underlying therapeutic response. Based on promising data from the PoP project, the proposed Extend-and-Confirm (EC) study will determine the efficacy of NAC in reducing AUD and comorbid PTSD in Veterans (N=90). Further, new aims include the application of functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (1H-MRS) to investigate the pathophysiology of AUD/PTSD, as well as prognostic indicators of treatment outcome. These aims extend the Future Plans proposed in the original PoP study and provide an opportunity for collaboration among clinical and preclinical investigators at the Ralph H. Johnson Veterans Affairs (VA) Medical Center and the Medical University of South Carolina (MUSC) to solve this critical health problem in the military context. In the proposed EC study, the investigators will (1) employ a randomized, double-blind, between-groups experimental design that will consist of 8 weeks of treatment with NAC (2400mg) or placebo medication, and follow-up assessment at 1-, 3-, and 6-months post treatment; (2) use standardized, repeated dependent measures to rigorously assess AUD severity and PTSD symptomatology during treatment and follow-up; (3) collect biologic measures of alcohol use; (4) measure impairment in associated areas of functioning (e.g., depression, sleep, suicidality, risky sexual behaviors, family/social functioning); and (5) employ advanced neuroimaging techniques before and after treatment among a subset of enrolled subjects. This proposal is directly responsive to the missions of the Institute for Translational Neuroscience (ITN), and the US Army/Department of Defense (DoD) in that it seeks to accelerate the development of new, medication-based treatments to mitigate the impact of AUD and comorbid psychological conditions, such as PTSD, in the military/Veteran context. The findings of this study will provide critically needed empirical evidence to help inform practice guidelines and better serve the needs of U.S. service members, Veterans and their families.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Posttraumatic Stress Disorder (PTSD), Alcohol Use Disorder (AUD), Substance Use Disorder (SUD)
Keywords
Alcohol, PTSD, Trauma, Veteran, Substance, Drug, Post Traumatic Stress Disorder, Military
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NAC/CBT
Arm Type
Experimental
Arm Description
Participants will receive N-acetylcysteine (NAC) and Cognitive Behavioral Therapy (CBT) for 8 weeks.
Arm Title
Placebo/CBT
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo pills and CBT for 8 weeks.
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine
Other Intervention Name(s)
NAC
Intervention Description
1200mg bid (2400mg/day)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo pills bid
Intervention Type
Behavioral
Intervention Name(s)
Cognitive behavioral therapy
Other Intervention Name(s)
CBT
Intervention Description
CBT for AUD/SUD, one hour/once a week
Primary Outcome Measure Information:
Title
Change in Alcohol Use Disorder Severity
Description
Change in Alcohol Use Disorder Severity as measured by change in average drinking days per week from baseline to week 8.
Greater reduction in drinking days indicates better treatment outcomes. Drinking days measured over 1 week periods (7 days). Scale ranges from 0 days to 7 days.
Time Frame
From baseline to week 8 of treatment
Title
Change in Post Traumatic Stress Disorder Severity
Description
Change in post traumatic stress disorder severity as measured by Change in Clinician Administered PTSD Scale (CAPS-5) score from baseline to week 8.
Greater change/reduction in score indicates better outcomes and greater reduction in PTSD symptomatology.
(minimum score of 0 = absent to a maximum score of 80 = extreme)
Time Frame
From baseline to week 8
Title
Change in Alcohol Craving
Description
Change in Alcohol craving as measured by change in Obsessive Compulsive Drinking Scale (OCDS) Total Score.
Greater change/reduction in score indicates better outcomes and reduced alcohol craving.
(Scores range from 0 to 56)
Time Frame
From baseline to week 8
Title
Change in Post Traumatic Stress Disorder Severity
Description
Post traumatic stress disorder symptoms as measured by change/reduction in score of post traumatic stress disorder checklist (PCL-5) from baseline to week 8.
Greater reduction in score indicates better treatment outcomes. (minimum score of 0 = absent to a maximum score of 80 = extreme)
Time Frame
From baseline to week 8
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudie Back, Ph.D.
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
Ralph H Johnson VA Medical Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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NAC for Treating Comorbid PTSD and SUD
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