Clinical trial NCT02911285
Conditions: Posttraumatic Stress Disorder (PTSD) Alcohol Use Disorder (AUD) Substance Use Disorder (SUD)
Keywords: Alcohol PTSD Trauma Veteran Substance Drug Post Traumatic Stress Disorder Military
Sponsor: Medical University of South Carolina
Start date: 2016-10-01; Completion date: 2019-11-04
Enrollment: 90 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Participants will receive N-acetylcysteine (NAC) and Cognitive Behavioral Therapy (CBT) for 8 weeks. arm 2: Participants will receive placebo pills and CBT for 8 weeks.
Interventions: intervention 1: N-acetylcysteine intervention 2: Placebo intervention 3: Cognitive behavioral therapy
Intervention descriptions: intervention 1: 1200mg bid (2400mg/day) intervention 2: Placebo pills bid intervention 3: CBT for AUD/SUD, one hour/once a week

Protocol documents:
Prot_SAP_000.pdf: 
Protocol: Glial Regulators for Testing Comorbid Posttraumatic Stress Disorder and Substance Use 
Disorders 
 
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Protocol: Glial Regulators for Testing Comorbid Posttraumatic Stress Disorder and Substance Use Disorders 
NCT:02911285 
PI: Sudie Back, PhD 
 


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Hypotheses 
Hypothesis 1: Participants receiving N-acetylcysteine (NAC), as compared to placebo, will demonstrate 
significantly greater reduction in SUD severity and craving from baseline to end of treatment (week 8).  
Hypothesis 2: Participants receiving N-acetylcysteine (NAC), as compared to placebo, will demonstrate 
significantly greater reduction in PTSD severity from baseline to end of treatment (week 8). 
Hypothesis 3:   Prefrontal cortex-amygdala connectivity at rest and in response to cues will predict reduction in 
SUD and PTSD severity.  
 
METHODS 
Overview: A randomized, double-blind, placebo-controlled clinical trial among individuals (N=90) with SUD and 
PTSD will be conducted to test the hypothesis that N-acetylcysteine (NAC) will significantly reduce SUD severity, 
craving, and PTSD symptoms. A subset of enrolled subjects between the ages of 21-40 will complete 
neuroimaging procedures before and after treatment. All procedures will be reviewed by the MUSC IRB and the 
Ralph H. Johnson VA Research and Development committee prior to study start. 
 
Participants: Ninety male and female participants between the ages of 18 to 75 with current AUD/SUD and 
comorbid PTSD or sub-threshold PTSD will be recruited to participate in the study.  
 
Recruitment: Primary recruitment sites include (1) the Ralph H. Johnson VAMC outpatient Substance 
Treatment and Recovery Clinic (STAR) and (2) the PTSD Clinical Team (PCT).  
 
Inclusion/Exclusion Criteria: To be included, subjects must (1) be 18-75 years old, (2) meet DSM-5 criteria for 
current PTSD or subthreshold PTSD, and (3) meet DSM-5 criteria for current AUD/SUD. Exclusion criteria 
include: (1) schizophrenia, bipolar disorder or an eating disorder; (2) any significant medical illness (e.g., asthma) 
that may adversely affect safety or study participation; (3) psychotropic medication initiation within 4 weeks of 
study participation or use of the following medications: carbamazepine, phenytoin, nitrous oxide, methotrexate, 
6-azauridine triacetate, nitroglycerin or any other medication that may have an adverse interaction with NAC; (4) 
pregnant or nursing women; and (5) clinically significant suicidal ideation and intent. 
 
General Procedures: Interested individuals will be screened for eligibility. Individuals who meet 
inclusion/exclusion criteria will be invited to come into the office for a comprehensive baseline assessment.  
Potential participants will be given a full description of the study and asked to read and sign an IRB-approved 
informed consent form before any study procedures or assessments are conducted. Baseline assessment will 
include diagnostic interviews, history and physical examination, assessment of concomitant medications, self-
report questionnaires, breathalyzer and urine drug screen (UDS), and pregnancy test for females. Ineligible 
participants will be referred clinically for treatment. Immediately following the baseline visit, eligible participants 
between the ages of 21-40 will complete a neuroimaging session (described in the Neuroimaging Component 
section) prior to medication initiation. This same subset of participants will complete a second neuroimaging scan 
during week 8 prior to medication discontinuation. All participants will enter an 8-week, randomized, double-
blind, placebo-controlled trial in which they will be seen once weekly. 
 
Study Medication, Dosage, and Administration: The starting and continuation dose of NAC will be 1200mg 
bid (2400mg/day). Medication will be dispensed weekly and participants will be asked to return the prior week’s 
medication container in order to account for unused medication and to assess medication compliance. Equivalent 
number of matching placebo capsules will be dispensed. Study medications (USP-grade NAC and matched 
placebo capsules) will be packaged by Pitt Street Pharmacy in Mount Pleasant, SC and dispensed to participants 
by the medical clinician. All NAC and placebo capsules will also contain riboflavin 25 mg, which will be used as 
a biomarker for medication compliance. Participants who wish to take a multivitamin during the treatment phase 
of the study will be given a multivitamin that does not contain riboflavin. Treatment assignment will follow a pre-


Protocol: Glial Regulators for Testing Comorbid Posttraumatic Stress Disorder and Substance Use 
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arranged randomization scheme and be carried out by a pharmacist not involved in clinical management of 
participants (to preserve the double-blind design). Subjects will be maintained at the target dose for 8 weeks. 
Side effects and adverse events will be evaluated weekly. 
Cognitive Behavioral Intervention: Participants will receive 1-hour each week of manual-based, cognitive 
behavioral therapy (CBT) for AUD/SUD. Receipt of weekly CBT during the treatment phase will facilitate retention 
and medication adherence, ensure that all participants receive adequate psychosocial support regardless of 
medication arm, and enhance statistical power (Carroll et al., 2004). Sessions from the Cognitive Behavioral 
Coping Skills Manual (Kadden et al., 2003) will be used, for example: Coping with Cravings and Urges to Use, 
Managing Thoughts about Alcohol/Drug Use, Problem Solving, Alcohol/Drug Refusal Skills, Planning for 
Emergencies and Coping with a Lapse, and Managing Negative Moods and Depression. All Study Therapists 
will complete a formal training of the intervention. To help maintain treatment integrity, we will use a manualized 
treatment, provide intensive bi-weekly supervision to reinforce and sustain clinicians’ skills in therapy delivery, 
and monitor fidelity to the treatment manual using methods developed in the NIMH Collaborative Study to prevent 
therapist “drift” (DeRubeis et al., 1982). 
 
Assessment Instruments: After the informed consent procedure, subjects will complete a battery of 
assessments. The instruments to be used were selected because many are standardized, have good 
psychometric properties, are widely used and have been used by our research group. The primary clinical 
outcomes include:  alcohol/substance use severity (TLFB), craving (OCDS), and PTSD symptom severity 
(CAPS-5).  
 
General Diagnostic and Inclusion/Exclusion Criteria 
• Demographics and Military Service Characteristics Form: This form measures demographics (e.g., age, race, 
gender, education, marital status) and military service information, such as branch and rank. 
• Treatment Services Review: This form obtains information about the participant’s ongoing/new treatment for 
alcohol/substance use and PTSD.    
• Mini International Neuropsychiatric Interview 7.0 (MINI 7.0; Sheehan et al., 1998): The MINI will be used to 
diagnose AUD, SUD, and confirm other exclusionary psychiatric diagnoses.  
• History of Head Injuries: A questionnaire that will be administered at Baseline, and Week 8 for anyone 
participating in fMRI, to assess for head injuries. 
 
Vital Signs, Adverse Events and Medication Compliance 
• Vital Signs: Orthostatic blood pressure, pulse measurements, weight and body mass index (BMI) calculations 
will be measured at baseline, Week 4, and Week 8.  
• Adverse Events (AEs): AEs will be assessed at baseline, weekly during treatment, and at follow-up. The type 
of AE, severity of the AE, duration of the AE, and relationship of AE to study medication will be recorded.  
• Concomitant Medications: All concomitant medications will be recorded on a standard form throughout the 
study. Multivitamins supplied by the study will be recorded and inquiries will be made about daily compliance. 
• Medication Accountability Log: This is a document describing a one-week schedule recording days of study 
medicine taken.  Returned medication packages will have capsules counted and recorded. 
• Riboflavin Test: All medication capsules, NAC and placebo, will contain 25mg of riboflavin. A urine assay will 
be collected at medication initiation (at baseline for telehealth participants), week 4 and week 8 to test for 
medication compliance.  
 
 
 
 
 
 
    


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Table 1.  Assessment Instruments and Timeline 
Instrument 
 
Baseline 
 
Medication 
Initiation 
Medication and Symptom Monitoring  
Follow
Up 
Weeks → 
-1 
0 
1 
2 
3 
4 
5 
6 
7 
8 
1 & 3 
Mth 
Demographic Data 
X 
 
 
 
 
 
 
 
 
 
 
History and Physical Examination 
X 
 
 
 
 
 
 
 
 
 
 
MINI Diagnostic Interviews 
X 
 
 
 
 
 
 
 
 
 
 
Concurrent Medications Form 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
X 
 
 
 
 
X 
 
 
 
X 
 
Medication Log 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urine Pregnancy Test for Females 
X 
 
 
 
 
X 
 
 
 
X 
 
Urine Drug Screen: UDS 
X 
 
 
 
 
X 
 
 
 
X 
X 
Riboflavin Test 
 
X 
 
 
 
X 
 
 
 
X 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Breathalyzer/Saliva BAC Tests  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Timeline Follow- Back: TLFB 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CIWA-AR 
X 
 
 
 
 
 
 
 
 
 
 
Visual Analog Scales; VAS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Obsessive Compulsive Drinking Scale: OCDS 
X  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Ethyl glucuronide (EtG) 
 
X 
 
 
 
X 
 
 
 
X 
 X 
Clinician Administered PTSD Scale: CAPS-5 
X 
 
 
 
 
X 
 
 
 
X 
X 
PTSD Checklist: PCL-5  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Life Events Checklist: LEC-5 
X 
 
 
 
 
 
 
 
 
 
 
Childhood Trauma Questionnaire: CTQ-SF 
X 
 
 
 
 
 
 
 
 
 
 
Beck Depression Inventory-II: BDI-II 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Deployment Risk & Resiliency Inventory-2 
X 
 
 
 
 
 
 
 
 
 
 
Columbia Suicide Severity Rating Scale 
X 
 
 
 
 
X 
 
 
 
X 
X 
Penetration of the Blind Questionnaire 
 
 
 
 
 
 
 
 
 
X 
 
AUDIT 
X 
 
 
 
 
 
 
 
 
 
 
Cognitive Testing 
 
X 
 
 
 
X 
 
 
 
X 
 
Blame Questionnaire 
X 
 
 
 
 
 
 
 
 
X 
 
Fagerstrom  
X 
 
 
 
 
 
 
 
 
 
 
Coping Inventory 
X 
 
 
 
 
 
 
 
 
X 
 
Visual Analog Scale: VAS - fMRI 
X 
 
 
 
 
 
 
 
 
X 
 
History of Head Injuries BL 
X 
 
 
 
 
 
 
 
 
 
 
History of Head Injuries FU 
 
 
 
 
 
 
 
 
 
X 
 
Satisfaction Questionnaire 
 
 
 
 
 
 
 
 
 
X 
X 
Treatment Services Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Neuroimaging Procedures 
■ 
 
 
 
 
 
 
 
 
■ 
 
Cognitive Behavioral Therapy: CBT 
 
 
♦ 
♦ 
♦ 
♦ 
♦ 
♦ 
♦ 
♦ 
 
  
Alcohol/Substance Use Disorder and Craving 
• Timeline Follow-Back (TLFB; Sobell & Sobell, 1992): The TLFB obtains retrospective self-report of substance 
use by using a calendar and memory prompts to stimulate recall. Quantity and frequency assessments are 
made using this instrument (e.g., total number of standard drink units, percent of days using) as well as 
abstinence (yes/no). TLFB yields consistently high test-retest correlations and correlates well with other self-
reports and collateral reports. The TLFB will assess consumption of alcohol (standard drink units) for 60 days 
prior to study entry, during the treatment and follow-up phase. Use of nicotine and other drugs of abuse, 
including prescription drugs, will also be assessed using the TLFB.  


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• Alcohol Breathalyzer Test will be used to measure blood alcohol concentration (BAC) on a weekly basis for in 
person visits. Samples reading >0.01 g/dl will be considered positive.  
• Alcohol Saliva Test will be used to measure blood alcohol concentration (BAC) on a weekly basis for telehealth 
visits. In front of the camera, participants will open the one time use test strip, place strip on tongue for 10 
seconds, then hold test strip and a color chart to the camera for a study team member to assess. Samples 
reading >0.01 g/dl will be considered positive. 
• Obsessive Compulsive Drinking Scale (OCDS; Anton et al., 1995): The OCDS is a 14-item self-report measure 
of craving with high internal consistency and concurrent validity, and good predictive validity of future drinking 
(Anton et al., 1995; Drobes & Thomas, 1999). It will be used to assess craving. 
• Visual Analog Craving Scale (VAS): A Modification of the Within Session Rating Scale (Childress et al., 1986) 
will be used to assess subjective ratings including craving (amount, frequency), stress and mood, with anchors 
from 0 = “none” to 10 = “extreme”.  
• Visual Analog Scale (VAS) fMRI: A modification of the Within Session Rating Scale (Childress et al., 1986) will 
be used to assess subjective ratings including craving and stress before and after the fMRI scan.   
• Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar; Sullivan et al., 1989): The CIWA-Ar is 
a widely used, 10-item clinician administered instrument that will be used to assess alcohol withdrawal 
symptoms. Subjects experiencing significant withdrawal, as evidence by a score of > 10, will be assessed by 
the Study Physician (Dr. Hamner) and referred clinically for medically supervised detoxification.  
• Alcohol Use Disorders Identification Test (AUDIT; Babor et al., 2001): The AUDIT is a 10-item self-report 
screening measure, developed by the World Health Organization (WHO), with three subscales (alcohol 
consumption, drinking behavior, and alcohol-related problems). Items are summed for a total score of 40. The 
AUDIT has good internal consistency (αs = .80-.93) as well as sensitivity and specificity.    
• Urine Drug Screen (UDS) tests: Urine samples will be tested with a Multi-Drug Panel Test, which allows for 
the detection of THC/Marijuana, Cocaine, Phencyclidine, Opioids, Methamphetamines, Amphetamines, 
Barbiturates, and Benzodiazepines.  
• Ethyl glucuronide (EtG): The conjugated alcohol metabolite EtG remains positive in urine for several days 
following cessation and is a useful biomarker of drinking in outpatient settings (Litten et al., 2010). This will be 
used as a biologic assessment of drinking, as breathalyzer tests only assess very recent alcohol use. The 
assay will be done at MUSC on samples collected at medication initiation, week 4, week 8 (end of treatment), 
and the follow ups.  
• Fagerstrom Test for Nicotine Dependence (FTND): Assesses the intensity of physical addiction to nicotine 
related to cigarette smoking. There are six questions that provide a total score range of 0-10, higher scores 
indicate a higher physical dependence (Heatherton, et al., 1991). It will be administered at baseline. 
 
Trauma History and PTSD 
• Clinician Administered PTSD Scale (CAPS; Weathers, Keane, & Davidson, 2001): The CAPS for DSM-5 is a 
30-item structured diagnostic interview and gold standard for assessing PTSD (Weathers et al., 2014). The 
CAPS has excellent psychometric properties and diagnostic efficiency (Weathers et al., 2001). The CAPS-5 
was revised to accommodate changes made in DSM-5, reduce administration time, and facilitate scoring 
procedures. 
• PTSD Checklist (PCL-5; Weathers et al., 2013): The PCL-5 is a 20-item self-report measure. The PCL-5 is 
similar in form to the PTSD Checklist (PCL) based on the DSM-5 (Weathers et al., 1993), which has excellent 
psychometric characteristics for screening and as a secondary indicator of PTSD symptom severity (McDonald 
& Calhoun, 2010). 
• Life Events Checklist for DSM-5 (LEC-5; Weathers et al., 2013): The LEC-5 assesses lifetime exposure to 
trauma. It includes the list of 16 different events from the original LEC. In addition, two items screen for military 
sexual trauma. The primary addition to the LEC-5 is a category involving occupational exposure (e.g., 
paramedic, police, or other first responder).  
• Childhood Trauma Questionnaire-Short Form (CTQ-SF; Bernstein et al., 2003): The CTQ is a 28-item self-
administered inventory that assesses childhood abuse and neglect. The CTQ-SF contains subscales including 
physical, sexual, and emotional abuse, and physical and emotional neglect.  


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• Coping Inventory for Stressful Situations: Situation Specific Coping (CISS: SCC): Assesses an individual’s 
coping preferences for a designated event (Endler & Parker, 1990).  
Depression and Suicidality 
• Beck Depression Inventory-II (BDI-II; Beck et al., 1996): The 21-item BDI-II is one of the most widely used 
instruments for measuring the severity of depressive symptoms. Total scores reflect minimal (0-13), mild (14-
19), moderate (20-28), or major depressive symptoms (29-63).  
• Columbia Suicide Severity Rating Scale (C-SSRS; Posner et al., 2007): The C-SSRS will be used to assess 
past/lifetime and current suicide ideation. It will be administered at baseline (for study eligibility), week 4 and 
week 8, and additionally as needed during the trial to monitor subject safety.  
Associated Areas of Functioning 
• Deployment Risk and Resiliency Inventory-2 (DRRI-2): The DRRI-2 (Vogt et al., 2012) is a suite of 17 individual 
scales that assess key deployment-related risk and resilience factors with demonstrated implications for 
Veterans’ long-term health. The following subscales will be used to assess deployment factors: Combat 
Experiences. We will use the Post-Deployment Life Events and Support scales to evaluate post-deployment 
factors for Veterans.   
• CNS Vital Signs Cognitive Testing: A battery of two tests (Stroop & Shifting Attention) will assess 
neurocognitive functions. 
 
Compensation: Participants will be compensated $50 for the baseline visit, $50 for each imaging visit, $40 for 
each completed weekly visit, and $75 for completing each of the follow-up visits. They will be given a $25 bonus 
if the baseline/first visit is attended as scheduled. Participants who previously consented to the optional 
neuropeptide Y will receive $15 compensation for completing the second blood draw. Thus, participants may 
receive up to $755 for completing all visits. Compensation is available in the form of cash, gift card, or check. 
 
Telehealth participants will be offered compensation for travel to and from the three mandatory in-person visits 
(Baseline, Week 4, & Week 8).  
 
Neuroimaging Component: Given the severe negative outcomes associated with co-occurring AUD/SUD and 
PTSD and lack of effective treatments, investigation of the neural circuitry and neurochemistry underlying 
AUD/SUD/PTSD and involved in positive therapeutic response could be important in guiding future treatment 
development studies. To that end, fMRI and 1H-MRS data will be acquired at baseline and end of treatment on 
a subset (n=40) of participants to examine (a) glutamate concentrations, (b) resting state connectivity, and (c) 
response to alcohol/drug, trauma, and neutral cues. Scans will be conducted at the MUSC Center for Biomedical 
Imaging.  
 
The neuroimaging component will involve three visits, each lasting 60-90 minutes. During visit 1, we will develop 
the personalized imagery scripts for alcohol/drug, trauma, and neutral cues. During visit 2 (pre-treatment) and 
visit 3 (end of treatment), we will conduct the fMRI and 1H-MRS scanning procedures. Imagery scripts will be 
similar to those developed according to standardized procedures (Sinha & Li, 2007) and employed in our ongoing 
research.  
 
Upon arrival to the imaging facility (Center for Biomedical Imaging), participants will first participate in a mock 
scanning session to acclimate to the MRI scanner and to practice using the joystick before completing the actual 
MRI scan. After mock scanning, participants will be screened for metal using a handheld metal detector. Trained 
staff will position individuals on the scanner bed with foam padding placed around their head to prevent motion. 
Participants will wear ear buds to listen to the audio-recorded scripts. For co-registration and normalization of 
functional images, a high resolution T1-weighted MPRAGE anatomical image will be acquired with the following 
parameters: TR = 2300ms, TE = 2.26ms, flip angle = 8°, field of view = 256mm, slice thickness 1.0mm. The 
scanning planes will be oriented parallel to the anterior commissure–posterior commissure line. The ACC voxel 
for 1H-MRS will be placed on midsagittal T1-weighted images, anterior to the genu of the corpus callosum, with 
the ventral edge of the voxel aligned with the dorsal edge of the genu and a voxel size of 3 x 2.5 x 2.5cm. 


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Following auto-shimming, single-voxel water-suppressed 1H-MRS spectra will be acquired using a Point 
Resolved Spectroscopy (PRESS) sequence: Repetition Time (RT) = 2000ms; Echo Time (TE) = 40ms; number 
of averages = 128; an unsuppressed water spectrum will be co-acquired (TE = 40ms, number of averages = 16), 
scaled for partial volume effects and relaxation, and used as a concentration reference (Mullins et al., 2008).  
 
Participants will be asked to relax and keep their eyes opened and fixed on a cross-hair for two six-minute runs 
while resting state data are collected. Following this, participants will be exposed to alcohol/drug, trauma and 
neutral cues, which will be audio recorded descriptions of the most recent time they used alcohol/drug, details 
of a traumatic event, and details about a relaxing event. 
 
We will use a block design consisting of a single run in which 4 task blocks alternate with rest blocks. The 4 task 
blocks consist of a neutral cue followed by a trauma cue followed by a neutral cue then an alcohol/drug cue. To 
minimize potential carry-over effects, the order of task blocks will be counterbalanced so that half of the subjects 
in the placebo group and half of the subjects in the NAC group are exposed to the alcohol/drug cue first and the 
remaining participants in each group are exposed to the trauma cue first. This order will be repeated at the end 
of treatment scan. T2*-weighted gradient-echo planar images (EPI) will be acquired with the following 
parameters: TR = 1100ms, TE = 30ms, flip angle = 65º, matrix 64 x 64, field of view = 192mm, slice thickness = 
3.0mm, with 48 slices to cover the entire brain. 
 
Statistical Analyses: Baseline clinical and demographic characteristics will be collected and contrasts 
performed between treatment groups. Baseline characteristics found to be significantly associated with primary 
outcome measures will be included as covariates in the analyses. In general, less than 10% missing data have 
little impact on power and do not introduce bias, regardless of the missing data mechanism. If the percent missing 
data are greater than 10%, propensity score methods will be used for data imputation. 
 
We plan to use REDCap for data capture and management. REDCap (Research Electronic Data Capture) 
is a software toolset and workflow methodology for electronic collection and management of research and 
clinical trial data (Harris et al., 2008; Harris et al., 2007). REDCap provides secure, web-­based flexible 
applications, including real time validation rules with automated data type and range checks at the time of 
entry. Exports are made available for several statistical packages including SPSS, SAS, SATA, R and 
Microsoft Excel.  
 
 
Power and Sample Size Estimation. It is expected that subjects treated with NAC, as compared to placebo, 
will exhibit significantly lower PTSD symptoms and craving at week 8. The effect sizes for these analyses (d = 
1.27, d = 1.03, respectively) are based on our PoP data. A sample size of 26 would provide power (1-ß) of .80 
to detect a large effect size with a Type 1 error protection level of .05 (Cohen, 1988). It is expected that NAC, as 
compared to placebo, will exhibit significantly lower AUD/SUD severity at week 8. To date, no published studies 
have examined NAC for the treatment of AUD. Assuming a medium effect size (d = .2), with a Type 1 error 
protection level of .05 and (1-ß) = .80, a total sample of 58 would be required. Recent unpublished pilot data 
conducted by our group examining the effects of NAC vs. placebo on standard number of drinks among patients 
with cocaine dependence and comorbid AUD (n=28) found a statistically significant treatment group effect. With 
regard to neuroimaging, a recent study of 29 individuals (PTSD=14, controls=15) observed significant differences 
in PFC-AMY resting state connectivity (Sripada et al., 2012). The effect size for this difference was 0.8 (Cohen’s 
d). Thus, power (1-ß) reaches .80 with a total sample size of N=26 (two-tailed, α = .05). Another study of 45 
cocaine-dependent individuals showed that lower PFC-AMY connectivity at baseline predicted relapse (McHugh 
et al., 2014). The effect size for this reduction was 1.0. Thus, power (1-ß) reaches .80 with N=34 subjects (two-
tailed, α = .05).  
 
Hypotheses: The hypotheses and statistical approaches for testing each hypothesis are listed below.  
 
Hypothesis 1: NAC treatment will result in significantly greater reduction in AUD/SUD severity and craving, as 
compared to placebo.  To test this hypothesis, a mixed effects modeling framework will be specified with the 


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total number of standard drinks consumed and the OCDS total score as the primary outcomes. A Poisson 
distribution will be assumed with a logarithm link function to assess the effects of NAC treatment. Data collected 
in substance abuse studies often contain a preponderance of zeros, and these zeros in the distribution can be 
considered sampling zeros in the Poisson process (Bandyopadhyay et al., 2011). If this excess is present in the 
distribution, two-part Hurdle models (Poisson and NB) will be explored (Cragg et al., 1971). The hurdle part of 
the model will allow us to estimate the probability of abstinence during the study period (as an odds ratio) while 
the Poisson/NB portion will allow for the assessment of the risk of an increase in using days beyond zero during 
the study period (as a risk ratio). Baseline alcohol/substance use and craving will be included in pertinent models 
as covariates. Additional alcohol/substance use outcomes will be assessed: change in percent drinking days, 
percent heavy drinking days, EtG, and VAS craving levels. 
 
Hypothesis 2: NAC treatment will result in significantly greater reduction in PTSD severity (CAPS-5) as compared 
to placebo. To test this hypothesis, generalized linear mixed effects regression models with a Gaussian 
distribution will be developed to assess group differences while adjusting for baseline CAPS-5 scores. 
Assumptions of residual normality and homoscedasticity will be checked using statistical test and graphical 
methods (Residual and Q-Q plots, and Shapiro-Wilk tests) and transformation will be done as necessary. 
Restricted maximum likelihood methods will be used to estimate the fixed effects and variance components. 
Additional outcomes (e.g., PCL-5, CAPS-5 symptom subscales) will be examined.  
 
Hypothesis 3A: Prefrontal cortex-amygdala connectivity at rest and in response to alcohol/drug vs. neutral cues 
will predict reduction in alcohol/substance use severity (total standard drinks). 
 
Hypothesis 3B: Prefrontal cortex-amygdala connectivity at rest and in response to trauma vs. neutral cues will 
predict reduction in PTSD severity (CAPS-5). 
 
For hypotheses 3A and 3B, the following preprocessing and analytical parameters will be used. Preprocessing: 
Post-acquisition preprocessing and statistical analysis of imaging data will be performed using FEAT (FMRI 
Expert Analysis Tool) Version 5.98, part of FSL (FMRIB's Software Library). Data will be preprocessed using 
scripting tools from FEAT. Non-brain signal will be removed using FSL’s BET brain extraction. Scans will be 
corrected for motion using FSL’s linear registration and scans will be spatially smoothed. Participants with head 
motion > 0.2 mm will be excluded from the analyses  (Power et al., 2012). Motion artifacts will be identified and 
scrubbed from each subject’s data. Scans will be spatially co-registered with a standardized anatomical template 
(Montreal Neurological Institute) using a 12 parameter affine transformation. Analysis: Functional connectivity 
will be measured using a psychophysiologic interaction (PPI) seed-based approach (Friston et al., 1997). PPI 
analysis is used to assess the functional coupling between different brain regions. The PPI is defined as the 
change in connectivity of one area (i.e., the seed region) to another in relation to the experimental context (e.g., 
alcohol vs. neutral cues). PPI analyses for resting state, trauma and alcohol/drug cues will be performed 
separately. Customized sq. wave forms representing the trauma run (1=trauma block and -1=neutral block) and 
the alcohol/drug cue run (1=alcohol/drug block and -1=neutral block) will be convolved with a double-gamma 
hemodynamic response function. A mask of the seed region will be made using a 12-mm diameter sphere 
located in the center of the AMY using the MNI coordinates (x, y, z = ±22, 0, -22). The transformation parameters 
described above will also be applied to the mask. For each subject, the mean corrected and high pass filtered 
time series of the BOLD signal in the AMY will be extracted and used in a single subject whole brain PPI analysis. 
The PPI model will include the task vector, time series of the BOLD signal in the AMY, a term representing the 
positive task x seed interaction, and a term representing the negative task x seed interaction. The first level 
analysis will generate contrast images of the parameter estimates for each of the four regressors. Voxels will be 
thresholded at Z > 2.3 using a corrected cluster threshold of p=0.05. The contrast images of the parameter 
estimates of the positive and negative task x seed interactions will be combined for group-level t-tests to identify 
regions that exhibited altered connectivity with the AMY during the trauma and alcohol/drug cues as compared 
to neutral cues. All group-level results will be thresholded at Z > 2.3 using a corrected cluster threshold of p=0.05. 
Separate linear regression tests will be used to test for associations between PFC-AMY connectivity at baseline 
and improvement in AUD/SUD and PTSD symptoms during treatment. Changes in total standard drinks will be 


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Disorders 
 
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regressed against the parameter estimate obtained from the center voxel from each cluster that exhibited a 
significant task x seed interaction with the AMY at rest and in response to the alcohol/drug cues (Hypothesis 
3A). Changes in CAPS-5 total scores will be regressed against the parameter estimate obtained from the center 
voxel from each cluster that exhibited a significant task x seed interaction with the AMY at rest and in response 
to the trauma cue (Hypothesis 3B). Further exploratory analyses will examine change in PFC-AMY connectivity 
from pre- to post-treatment and associations with other alcohol/drug and PTSD outcomes, both within and 
between medication groups. 
 
 
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Schneider, R.J., Santos, C.F., Clarimundo, V., Dalmaz, C., Elisabetsky, E., & Gomez, R. (2015). N-
acetylcysteine prevents behavioral and biochemical changes induced by alcohol cessation in rats. 
Alcohol, 49(3), 259-263.  
Seal, K.H., Bertenthal, D., Miner, C.R., Sen, S., & Marmar, C. (2007). Bringing the war back home: Mental health 
disorders among 103,788 US veterans returning from Iraq and Afghanistan seen at Department of 
Veterans Affairs facilities. Archives of Internal Medicine, 167, 476-482. 
Seal, K.H., Cohen, G., Waldrop, A., Cohen, B.E., Maguen, S., & Ren, L. (2011). Substance use disorders in Iraq 
and Afghanistan veterans in VA healthcare, 2001-2010: Implications for screening, diagnosis and 
treatment. Drug and Alcohol Dependence, 116(1-3), 93-101.  
Seeley, W.W., Menon, V., Schatzberg, A.F., Keller, J., Glover, G.H., Kenna, H., . . .   Greicious, M.D. (2007). 
Dissociable intrinsic connectivity networks for salience processing and executive control. Journal of 
Neuroscience, 27(9), 2349–2356.  
Selim, A.J., Rogers, W., Fleishman, J.A., Qian, S.X., Fincke, B.G., Rothendler, J.A., & Kazis, L.E. (2009). 
Updated U.S. population standard for the Veterans RAND 12-item Health Survey (VR-12). Quality of Life 
Research, 18(1), 43-52. 
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., & Dunbar, G.C. (1998). The 
Mini-International Neuropsychiatric Interview (M.I.N.I.). Journal of Clinical Psychiatry, 59, 22-33. 
Sinha, R., & Li, C.R. (2007). Imaging stress- and cue-induced drug and alcohol craving: Association with relapse 
and clinical implications. Drug and Alcohol Review, 26(1), 25-31. 
Smith, T.C., Ryan, M.K., Wingard, D.L., Slymen, D.J., Sallis, J.F., & Kritz-Silverstein, D. (2008). New onset and 
persistent symptoms of posttraumatic stress disorder self reported after deployment and combat 
exposures: Prospective population based US military cohort study.  British Medical Journal, 336(7640), 
366-371.  
Sobell, L.C., & Sobell, M.B. (1992). Timeline follow-back: A technique for assessing self-reported alcohol 
consumption. In R. Z. Litten, & J. P. Allen (Eds.), Measuring Alcohol Consumption: Psychosocial and 
Biochemical Methods (pp 41-72). Humana Press. 
Sofuoglu, M., Rosenheck, R., & Petrakis, I. (2014). Pharmacological treatment of comorbid PTSD and substance 
use disorder: Recent progress. Addictive Behaviors, 39(2), 428-433. 
Substance Abuse and Mental Health Services Administration. (2007). Results from the 2006 national survey on 
drug use and health: National Findings. Rockville, MD: Office of Applied Studies. 
Sullivan, J.T., Sykora, K., Schneiderman, J., Naranjo, C.A., & Sellers, E.M. (1989). Assessment of alcohol 
withdrawal: Revised Clinical Institute Withdrawal Assessment for Alcohol scale. British Journal of 
Addiction, 84, 1353-1357. 
Spera, C., Thomas, R.K., Barlas, F., Szoc, R., & Cambridge, M.H. (2011). Relationship of military deployment 
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of Alcohol and Drugs, 72(1), 5-14.  
Sripada, R.K., King, A.P., Welsh, R.C., Garfinkel, S.N., Wang, X., Sripada, C.S., & Liberzon, I. (2012). Neural 
dysregulation in posttraumatic stress disorder: Evidence for disrupted equilibrium between salience and 
default mode brain networks. Psychosomatic Medicine, 74(9), 904-911. 
Tanielian, T., & Jaycox, L.H. (2008). Invisible wounds of war: Psychological and cognitive injuries, their 
consequences, and services to assist recovery. Santa Monica, CA: RAND Corp, 97. 
Torchalla, I., Nosen, L., Rostam, H., & Allen, P. (2012). Integrated treatment programs for individuals with 
concurrent substance use disorders and trauma experiences: A systematic review and meta-analysis. 
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posttraumatic stress disorder and substance use disorder: A systematic review. Clinical Psychology 
Review, 32(3), 202-214.  


Protocol: Glial Regulators for Testing Comorbid Posttraumatic Stress Disorder and Substance Use 
Disorders 
 
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Vogt, D.S., Smith, B.N., King, L.A., King, D.W., Knight, J.A., & Vasterling, J.J. (2013). Deployment Risk and 
Resilience Inventory-2 (DRRI-2): An updated tool for assessing psychosocial risk and resilience factors 
among service members and veterans. Journal of Traumatic Stress, 26, 710-717.  
Weathers, F.W., Blake, D.D., Schnurr, P.P., Kaloupek, D.G., Marx, B.P., & Keane, T.M. (2013). The Life Events 
Checklist for DSM-5 (LEC-5). Instrument available from the National Center for PTSD. 
Weathers, F.W., Marx, B.P., Friedman, M.J., & Schnurr, P.P. (2014). Posttraumatic  stress disorder in DSM-5: 
New criteria, new measures, and implications for assessment. Psychological Injury and Law, 7(2), 93-
107.  
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approach to obtain informed consent for research. Contemporary Clinical Trials Communications, 3, 74-
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Wolfe, D.J. & Kalivas, P.W. (2015). Glutamate transporter GLT-1 as a therapeutic target for substance use 
disorders. CNS and Neurological Disorders -  Drug Targets, 14(6), 745-56. 
Young, H.E., Rosen, C.S., & Finney, J.W. (2005). A survey of PTSD screening and referral practices in VA 
addiction treatment programs. Journal of Substance Abuse Treatment, 28(4), 313-319. 
 
 

ICF_001.pdf: 
Title:  NAC for Treating Comorbid PTSD and SUD
Informed Consent Documents
ID: Pro00052757


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Medical University of South Carolina 
CONSENT TO BE A RESEARCH SUBJECT 
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and Substance Use Disorders 
 
A. Purpose and Background 
You are invited to take part in a research study being sponsored by the United States Department of Defense and the 
Institute for Translational Neuroscience at the University of California, San Francisco. You are being invited to take part 
in this study because you are between 18-75 years of age, may have an alcohol or substance use disorder and symptoms of 
posttraumatic stress disorder (PTSD). The investigator in charge of this study is Dr. Sudie Back at the Medical University 
of South Carolina (MUSC). This study is being conducted in Charleston, SC and will involve approximately 90 
participants.   
Please read this consent form carefully because it explains what to expect with this study.  Feel free to ask any questions 
now, or at any time during this study.  All study procedures for this study will take place at MUSC. However, you may 
also be asked to sign a consent form for the VA if you are a patient there and the initial contact for this study took place at 
the VA.  
The purpose of this study is to determine whether Cognitive Behavior Therapy combined with a dietary supplement called 
N-acetylcysteine (NAC) is effective in reducing alcohol/drug use severity and PTSD symptoms. In addition, there is a 
neuroimaging portion of this study which will involve the first 40 participants who are 21-40 years of age and interested in 
participating.  
NAC has been approved by the US Food and Drug Administration (FDA) in an inhalant form for the treatment of chronic 
lung conditions.  It is also FDA-approved in a liquid and intravenous (IV) form to treat people who have overdosed on 
acetaminophen (Tylenol® and other names).  Thousands of patients world-wide have used this form of NAC for the 
treatment of acetaminophen overdose.  You will receive either NAC or placebo in a capsule. Because NAC is not approved 
by the FDA for treating substance use disorders or PTSD, it is called an investigational drug.   
B. Procedures 
This study will include a 1 to 2 week screening period followed by an 8-week medication phase.  During the medication 
phase you will be asked to come into the clinic for 1 visit each week.  We will also ask you to come back to the clinic for 
follow-up visits about 1 and 3  months after you finish the medication.   
If there is anything that makes it difficult for you to come to MUSC, you may choose to do your study visits and therapy 
sessions via home-based telehealth (HBT) (weeks 1, 2, 3, 5, 6, & 7 only; sessions 4 and 8 will require an in-person visit).  
HBT allows a therapist and patient who are not in the same room together to communicate.  This is usually done over the 
computer using MUSC-approved teleconferencing applications.  In order to complete sessions via HBT, you will need to 
have internet or cellular access in your home and a computer, tablet, or smartphone capable of accessing the internet. If 
needed, a webcam can be provided for the duration of the study. Barriers to being unable to come to MUSC for face to face 
treatment varies, but typically involves transportation, financial, or child care issues. 
Screening and Baseline Phase (1 to 2 weeks) 
During the 1 to 2 week screening phase, you will be asked questions about, for example, your age, employment, relationship 
status, and education.  Prior medications will be recorded and a psychiatric evaluation will be done which will assess 
symptoms of PTSD and other psychiatric conditions in order to determine if you are eligible for the study. You will be also 
asked questions about your use of alcohol and drugs. A history and physical examination will be conducted, as well as an 
alcohol breathalyzer test, urine drug screen test, and pregnancy test (for women). If your pregnancy test is positive, your 
participation in this study will end and no further testing will be done.  


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Participant Enrollment 
At the end of the screening period a medical clinician will determine if you are able to participate in the study. Therefore, 
even if you signed the consent form you may not be able to participate in this study. If you are eligible to continue you will 
be enrolled into the medication phase.  
Medication Phase (8 weeks) 
During this phase you will be given in random order (like the flip of a coin) either NAC 2400mg/day or placebo (a pill 
without medication). Neither you nor the study staff seeing you will know if you are taking NAC or placebo.  Only the 
pharmacist who prepares the medication will know if you are on NAC or placebo until the entire study is over.  You will 
be given capsules to take daily during the 8 weeks. All capsules will include riboflavin, a vitamin supplement which may 
cause your urine to be orange in color. This allows the investigators to be sure you are taking the medication. If you are 
already taking a multi-vitamin with riboflavin in it at the beginning of the study, you will be asked to stop taking the multi-
vitamin and the study will give you a multi-vitamin that does not contain riboflavin. 
You will be given a 1-week supply of medication or placebo at the beginning of each week, typically on Monday or 
Tuesday, and will be asked to self-report at home on a calendar the daily timing of capsules taken and bring back the form 
and any unused capsules at the next visit. 
You will be asked to come to the clinic or meet via telehealth once a week during the medication phase. You will meet 
with a study team member on a weekly basis to monitor your health, side effects and use of other medications.  Pregnancy 
tests for women will be done monthly during this phase. Should your pregnancy test be positive, this will end your 
participation and no further testing will be done. The weekly clinic visits will last about 1.5-2.5 hours and consist of a 
breathalyzer/saliva test, self-report questionnaires about alcohol/drug use, PTSD and mood, and a therapy session. 
Telehealth participants will be required to complete the saliva alcohol test in front of the camera (test strip held on tongue 
for ten seconds) which will allow a study team member to assess and validate test results. During the treatment phase you 
will complete 8 individual therapy sessions. These therapy sessions will involve helping you identify and change unhelpful 
thoughts and behaviors related to alcohol/drug use.  The therapy in this research study will be in individual format and will 
be conducted by a well-trained clinician working under the supervision of project investigators who are clinical 
psychologists and medical doctors. 
At the end of the medication phase (week 8), you will stop taking the study medication.  No additional study medication 
will be given.  
 
Follow-up Phase  
You will be asked to return to the clinic or meet via telehealth about 1 and 3 months after the medication phase for 
questionnaires, assessment of substance use and PTSD symptoms, and alcohol breathalyzer/saliva and urine tests. You will 
not receive study medication during the follow-up phase.  You will also be asked to report any side effects, such as dizziness 
and headaches, you may have had since your last clinic visit.  If you cannot be reached directly for this follow-up visit, 
attempts will be made to reach you by contacting people identified by you in your locator form. This will only be done to 
verify your physical well-being and safety. 
 
Neuroimaging Portion of the Study  
If you choose to participate in the neuroimaging (i.e., brain scan) portion of the study, you will be asked a series of questions 
regarding the presence of metallic items in or on your body and about any brain injuries. If you are eligible to participate 
in the scanning session, you will be scheduled for 2 magnetic resonance imaging (MRI) scanning sessions – the first will 
be before you begin taking the study medication and the second will be during the final week (week 8) of taking the study 
medication. You will be asked to meet the study personnel at the Center for Biomedical Imaging (CBI) at 30 Bee Street, 
which is on the MUSC campus, for the neuroimaging visits.    
 
The neuroimaging sessions will last approximately 1.5 hours each. When you arrive, you will be asked the same series of 


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questions regarding the presence of metallic items in your body. If you are female, you will also be asked to provide a urine 
sample for a pregnancy test. If you are pregnant, or if there are any metallic items in your body that prevent safe MRI 
scanning, you will not be eligible to participate further in the MRI portion of this investigation.  
 
The MRI is a large doughnut shaped machine. You will be given earplugs to wear while you are in the scanner. You will 
be able to speak to and hear the research staff during the scan.  We will first ask you to lay still and close your eyes while 
we take images of the structure of your brain. Following the structural images, we will acquire functional images of your 
brain activity while you listen to recordings describing your recent experiences with alcohol/drugs, a traumatic event, and 
neutral cues.  The same procedures will be followed during the first and the second neuroimaging visits.   
If you are 21-40 years old, please initial by your choice below:  
 
____ Yes, I would like to participate in the neuroimaging visits.  
 
____ No, I do not want to participate in the neuroimaging visits.  
 
____ N/A, I am not between the ages of 21-40. 
 
C.  Duration 
The total time in the study will be approximately 22 weeks consisting of:  
1) The screening and baseline phase takes 1 to 2 weeks. You will be asked to come in for up to 3 visits during this 
phase with the first visit lasting about 3 to 4 hours (assessment to determine eligibility to participate in the study), 
the second lasting about 1.5 hours (neuroimaging scan) and the third visit (medication start) lasting about 1 hour.  
 
2) The medication phase will last 8 weeks. During this phase, you will be asked to come to the clinic once a week or 
meet via telehealth for visits lasting about 1.5-2.5 hours.  The longer visit during week 4 and week 8 will take about 
2.5 hours because of additional questionnaires during those visits and will require coming into the clinic. The final 
neuroimaging scan will take place during week 8 of the treatment phase and will last about 1.5 hours.  
 
3) The follow-up phase involves visits at 1 and 3 months after you stop taking the medication. These visits should take 
about 1.5 to 2 hours to complete. 
 
D. Possible Discomforts and/or Risks 
You will have to take time to come to the clinic or meet via telehealth during the screening, medication and follow-up 
phases of the study. Therefore, being in this study may cause inconvenience in your schedule at times.  Some of the 
questions about your personal life, substance use, or PTSD symptoms may embarrass you or cause you distress or boredom.  
You may have some side effects from the study medication.  The side effects most common in people who take NAC by 
mouth include nausea, headache, vomiting and diarrhea. These side effects are usually mild and go away even with 
continued use of NAC by mouth.  In this study, NAC will only be given by mouth. In addition to the side effects listed 
above, a skin rash has happened in about 10% of subjects participating in previous studies. If you develop a rash, you will 
be removed from the study medication and will be looked at by a study physician. You may, if necessary, be treated with 
an antihistamine (example: Benadryl) or another medication to help out with the rash.   
It is highly unlikely (probably less than one chance in several thousand) that you will have a severe allergic reaction to the 
NAC. If you have trouble breathing, the emergency medical system (EMS - call 911) should be called, and you should be 
transported to the nearest emergency room for immediate treatment.  Because NAC has not been studied in combination 
with very many other medications, it will be important for you to report to the research staff any medications you may be 


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taking before, during, or after the medication phase.  Medications include prescription medications from a doctor, over-
the-counter medications that you may buy in a drug store, herbal medications that you may buy in a health-food store, or 
“street” drugs. 
There are known psychological risks associated with withdrawal from many substances of abuse including increased 
sleepiness, unhappy mood, craving, and irritability.   
You will be asked to answer questions about your substance use, legal history and lifestyle.  The risk of release of this 
sensitive, confidential information will be kept to a minimum by storing your information in locked cabinets that are in 
locked offices.  The research staff that will be working with you has been thoroughly trained to keep your information 
confidential.  
There is a chance that you will receive a placebo pill (a pill without medication) instead of the study medication.  There is 
a chance that NAC or placebo may not reduce your desire to use alcohol/drugs or your PTSD symptoms.  There is also a 
chance that your alcohol/drug use or PTSD symptoms may worsen while you are in this study.  The research or procedures 
may involve risks that are currently unforeseeable but your health will be monitored closely to minimize the possibility of 
side effects. 
The safety of NAC in pregnancy and in nursing mothers is unknown.  Therefore, all women will be given a urine pregnancy 
test during screening and monthly during the medication phase.  No pregnant women or nursing mothers may be in this 
study. Women must use a medically acceptable form of birth control while participating in the study.  Acceptable forms of 
birth control are: an oral contraceptive (birth control pills), diaphragm or a condom used with a spermicide, intrauterine 
progestive 
contraceptive 
system 
(Progestacert®), 
levonorgestrel 
implant 
(Norplant®), 
medroxyprogesterone 
(Depoprovera®) injection contraception, surgical sterilization, or complete abstinence from sexual intercourse during the 
entire study.  If you become pregnant during the study, you will be taken off the study medication and your participation 
in the study must end. If you wish, you will be referred for regular clinical treatment.  If you become pregnant and test 
positive for illegal drugs, it is a law that the South Carolina Department of Social Services (DSS) must be notified.  You 
and your family will be evaluated by the agency.  You could be ordered to mandatory drug treatment, lose custody of your 
children, or possibly be jailed. 
Potential risks of Neuroimaging: 
The risk from MRI is low. No radiation or x-rays are used in making pictures of your brain during the MRIs. You cannot 
have an MRI scan if you have metal in the skull, metal implants, a cardiac or brain pacemaker, or old metal fragments in 
the eye or retina.  If you have a question about metal in your body, you should inform the researchers and they will 
determine whether it is safe in an MRI scanner.  Some discomfort may occur from having to remain still for a while in the 
scanner.  There is no exposure to ionizing radiation, nothing will be injured, and no blood will be taken. The MRI scanner 
is noisy, and there is a risk of hearing damage if you do not wear earplugs. To eliminate this risk, you will be given earplugs 
to wear during each scan.  
Although the MRI scanner is open on both ends, some people become anxious when entering the MRI scanner due to the 
feeling of being enclosed. If this has happened to you in the past, you should inform the study personnel. To address this 
concern, all participants will be given an emergency call button which they can activate at any time during the scan if they 
are feeling uncomfortable in the MRI scanner. If this indicator is activated the study personnel will come into the scanning 
room immediately and take you out of the scanner.  
 
E. Possible Benefits 
There are no guarantees that you will directly benefit from taking part in the study. Based on experience with NAC and 
cognitive behavioral therapy in patients with similar disorders, researchers believe it may be of benefit to people with your 
conditions. Of course, because people respond differently to medications and behavioral therapies, no one can know in 
advance if it will be helpful for you.  Being in this research study may reduce your alcohol/drug use and PTSD symptoms, 


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and it may also help in the understanding of how safe and effective NAC is in treating these conditions. Another benefit is 
that the information gained from the study will help increase our knowledge about how to best treat individuals with PTSD 
and substance use disorder. 
 
F. Cost of Participation 
You will not be charged for any of the study treatments or procedures. The costs of medication and all tests associated with 
this study and all visits will be covered by the study. Your normal data and usage rates will apply if you choose to use a 
cellular phone or cellular data enabled device for telehealth sessions. 
 
G.   Payment to Participants 
You will be compensated for providing data and for your time while in this research study. You will receive $50 for the 
baseline visit, $50 for each imaging visit, and up to $40 for each weekly visit ($20 study visit, $20 therapy session). You 
will also receive $75 for each follow-up visit at 1 and 3 months after treatment.  Thus, the total amount you may receive 
for your study participation is $755. Compensation can be provided by cash (in-person pick up only), gift card (in-person 
pick up only), or check (requires mailing address and full social security number, may take 4-6 weeks to arrive). 
 
Telehealth participants will be offered compensation for travel to and from the three mandatory in-person visits (Baseline, 
Week 4, & Week 8). Also, if the baseline visit is four hours or longer, telehealth participants will be offered a meal. 
 
Referrals 
You are invited to participate in the recruitment of other subjects for this study.  If you choose to participate, we will 
provide you with cards that you may give to other people (e.g., friends, acquaintances) who you think would be eligible 
and interested in this study.  You may choose to tell people to whom you give these cards to call the study office if they 
are interested in participating in the study.  These individuals will not be identified unless they contact the study office 
themselves.  If any of the cards you are given result in successful study recruitment, you will receive $10 for each referred 
individual who enrolls in the study. Participation in the recruitment process is completely voluntary and if you elect not to 
participate, your participation in this study will not be affected in any way. 
 
Payments that you receive from MUSC for participating in a research study are considered taxable income per IRS 
regulations. Payment types may include, but are not limited to: checks, cash, gift certificates/cards, personal property, and 
other items of value.  If the total amount of payment you receive from MUSC reaches or exceeds $600.00 in a calendar 
year, you will be issued a form 1099.  
 
H. Alternatives 
If you do not want to be in this study, other ways of treating substance use problems and PTSD are individual or group 
counseling, as well as several FDA approved medications. If you would like, we will refer you to clinical treatment. You 
will be responsible for the costs of treatment. 
 
Withdrawal from the Study 
Your participation in this study is voluntary. You may refuse to take part in or stop taking part in this study at any time. 
You should talk with the investigator in charge of this study if you decide to do this. Your decision not to take part in the 
study will not affect your current or future medical care or any benefits to which you are entitled. The investigators and/or 
the sponsor may stop your participation in this study at any time if they decide it is in your best interest. They may also do 
this if you do not follow the investigator’s instructions. If your participation is ended for medical reasons, you will be 
referred to a doctor or other health professional for care. You will be responsible for the cost of these services. 
I.  Disclosure Of Results 


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You may request to receive a report of the aggregate results following completion of the study. 
 
 
J. New Information 
If there are significant new findings during the course of the study, you will be notified. These new findings include, but 
are not limited to, changes in the potential risks or benefits resulting from being in the research or new alternatives to being 
in this study, which might cause you to change your mind about continuing in the study.  If new information is provided to 
you, your consent to continue taking part in this study will be re-obtained.  
 
K. Release Of Medical Records To Anyone Other Than The Investigators 
If for any reason you would like your study records released to anyone other than the investigators, you will be asked to 
sign an additional release of information form. You will also be asked to sign a Health Insurance Portability and 
Accountability Act (HIPAA) Authorization to use or disclose your protected health information for research purposes.  
 
L. Student Participation 
Your participation or discontinuance will not constitute an element of your academic performance nor will it be part of 
your academic record. 
 
M. Employee Participation 
Your participation or discontinuance will not constitute an element of your job performance or evaluation nor will it be 
part of your employee record. 
 
N. Invitation To Participate In Future Studies 
In the future, MUSC may be conducting other related studies. Please let us know your interest in being re-contacted in the 
future by telephone, mail or email about other studies that you may qualify for: 
 
____ Yes, I am interested in being contacted about future studies. 
____ No, I am not interested in being contacted about future studies. 
 
O. Clinical Trial Registry Databank 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This web 
site will not include information that can identify you. At most, the web site will include a summary of the results. You 
can search this web site at any time. 
P. Sponsor Commitment Section 
The Department of Defense will not pay for any medical treatment in the event of a study related injury. 
Q. Contact 
You have the option of receiving appointment reminders and links to study surveys through text messages. 
Should you elect to receive text messages, normal cellular data usage and rates will apply. Please indicate your 
choice below: 
____Yes, I agree to be contacted via text message 
____No, I do not agree to be contacted via text message 
 
 
 
 


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Confidentiality: 
We will take careful precautions to maintain your confidentiality, using procedures that we have successfully employed in 
similar previous as well as ongoing studies. All study data related to psychological outcomes (i.e., the responses to 
questionnaires) and demographics will not have any unique identifying data attached in any way. There will be a master 
list of participants (again, not linked to any participant responses) which will be kept separate from all data and will be 
available only to Dr. Back and approved study personnel. All data will be stored in a confidential manner (i.e., in locked 
files or on encrypted computers in the Study Coordinator’s or Research Assistant’s office). Access to research records 
(paper and computerized) will be restricted to the project staff, sponsor audit personnel, VAMC R&D auditors, and MUSC 
IRB auditors. Neuroimaging data will be stored on a secure password protected server maintained by MUSC’s Center for 
Biomedical Imaging (CBI). Only Dr. Back and approved study personnel will have access to the files on the secure CBI 
server.  
 
CONSENT 
Results of this research will be used for the purposes described in this study. This information may be published, but you 
will not be identified. Information that is obtained concerning this research that can be identified with you will remain 
confidential to the extent possible within State and Federal law. The sponsor and the Food and Drug Administration (FDA) 
will receive copies of the research records. The investigators associated with this study, employees of the sponsor, the 
FDA, and the MUSC Institutional Review Board for Human Research will have access to identifying information. All 
records in South Carolina are subject to subpoena by a court of law. 
In the event of a study related injury, you should immediately go to the emergency room of the Medical University Hospital, 
or in case of an emergency go to the nearest hospital, and tell the physician on call that you are in a research study. They 
will call your study doctor who will make arrangements for your treatment. If the study sponsor does not pay for your 
treatment, the Medical University Hospital and the physicians who render treatment to you will bill your insurance 
company. If your insurance company denies coverage or insurance is not available, you will be responsible for payment 
for all services rendered to you. 
Your participation in this study is voluntary. You may refuse to take part in or stop taking part in this study at any time. 
You should call the investigator in charge of this study if you decide to do this. The data collected on you to this point 
remains part of the study database and may not be removed. Your decision not to take part in the study will not affect your 
current or future medical care or any benefits to which you are entitled. 
 
 
 
 


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Volunteers Statement 
I have been given a chance to ask questions about this research study. These questions have been answered to my 
satisfaction. If I have any more questions about my participation in this study or study related injury, I may contact Dr. 
Sudie Back at (843) 792-9383. I may contact the Medical University of SC Hospital Medical Director (843) 792-9537 
concerning medical treatment.  
If I have any questions, problems, or concerns, desire further information or wish to offer input, I may contact the Medical 
University of SC Institutional Review Board for Human Research IRB Manager or the Office of Research Integrity Director 
at (843) 792-4148. This includes any questions about my rights as a research subject in this study. 
I agree to participate in this study. I have been given a copy of this form for my own records. 
If you wish to participate, you should sign below. 
                                                                                  
                                                                          
Signature of Person Obtaining Consent 
    Date 
Signature of Participant 
    Date 
  
 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 1 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
A. Purpose and Background 
You are invited to take part in a research study sponsored by the United States Department of Defense and the 
Institute for Translational Neuroscience at the University of California, San Francisco. You are being invited to 
take part in this study because you are a Veteran between 18-75 years of age who may have a substance use 
disorder and symptoms of posttraumatic stress disorder (PTSD). The investigator in charge of this study is Dr. 
Sudie Back at the Medical University of South Carolina (MUSC) and the Ralph H. Johnson Veteran’s Medical 
Center (VAMC). This study is being conducted in Charleston, SC and will involve approximately 90 
participants.   
Please read this consent form carefully because it explains what to expect with this study.  Feel free to ask any 
questions now, or at any time during this study.  The study procedures for this study will take place at the 
VAMC and MUSC.   
The purpose of this study is to determine whether Cognitive Behavior Therapy combined with a dietary 
supplement called N-acetylcysteine (NAC) is effective in reducing alcohol/drug use severity and PTSD 
symptoms. In addition, there is a neuroimaging portion of this study which will involve the first 40 participants 
who are 21-40 years of age and interested in participating.  
NAC has been approved by the US Food and Drug Administration (FDA) in an inhalant form for the treatment 
of chronic lung conditions.  It is also FDA-approved in a liquid and intravenous (IV) form to treat people who 
have overdosed on acetaminophen (Tylenol® and other names).  Thousands of patients world-wide have used 
this form of NAC for the treatment of acetaminophen overdose. Because NAC is not approved by the FDA for 
treating substance use disorders, it is called an investigational drug.   


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 2 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
B. Procedures 
This study will include a 1 to 2 week screening period followed by an 8-week medication phase.  During the 
medication phase you will be asked to come into the clinic for 1 visit each week.  We will also ask you to come 
back to the clinic for follow-up visits about 1 and 3 months after you finish the medication.   
If there is anything that makes it difficult for you to come to the Ralph H. Johnson VA, you may choose to do 
your study and therapy sessions via home-based telehealth (HBT) (weeks 1, 2, 3, 5, 6, & 7 only; weeks 4 & 8 
will require an in-person visit).  HBT allows a therapist and patient who are not in the same room together to 
communicate.  This is usually done over the computer using VA-approved teleconferencing software.  In order 
to complete sessions via HBT, you will need to have high speed internet access in your home and a computer or 
tablet capable of downloading VA-approved videoconferencing software.  If needed, a webcam can be provided 
for the duration of the study. Barriers to being unable to come to the VA for face to face treatment varies, but 
typically involves transportation, financial, or child care issues. 
Screening and Baseline Phase (1 to 2 weeks) 
During the 1 to 2 week screening phase, you will be asked questions about, for example, your age, employment, 
relationship status, and education.  Prior medications will be recorded and a psychiatric evaluation will be done 
which will assess symptoms of PTSD and other psychiatric conditions in order to determine if you are eligible 
for the study. You will be also asked questions about your use of alcohol and drugs. A history and physical 
examination will be conducted, as well as an alcohol breathalyzer test, urine drug screen test, and pregnancy test 
(for women). If your pregnancy test is positive, your participation in this study will end and no further testing 
will be done.  
 
Participant Enrollment 
At the end of the screening period a medical clinician will determine if you are able to participate in the study. 
Therefore, even if you signed the consent form you may not be able to participate in this study. If you are 
eligible to continue you will be enrolled into the medication phase.  
 
 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 3 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
Medication Phase (8 weeks) 
During this phase you will be given in random order (like the flip of a coin) either NAC 2400mg/day or placebo 
(a pill without medication). Neither you nor the study staff seeing you will know if you are taking NAC or 
placebo.  Only the pharmacist who prepares the medication will know if you are on NAC or placebo until the 
entire study is over.  You will be given capsules to take daily during the 8 weeks. All capsules will include 
riboflavin, a vitamin supplement which may cause your urine to be orange in color. This allows the investigators 
to be sure you are taking the medication. If you are already taking a multi-vitamin with riboflavin in it at the 
beginning of the study, you will be asked to stop taking the multi-vitamin and the study will give you a multi-
vitamin that does not contain riboflavin. 
 
You will be given a 1-week supply of medication or placebo at the beginning of each week, typically on 
Monday or Tuesday, and will be asked to self-report at home on a calendar the daily timing of capsules taken 
and bring back the form and any unused capsules at the next visit. 
You will be asked to come to the clinic once a week or meet via telehealth during the medication phase. You 
will meet with a study team member on a weekly basis to monitor your health, side effects and use of other 
medications.  Pregnancy tests for women will be done monthly during this phase. Should your pregnancy test be 
positive, this will end your participation and no further testing will be done.  
The weekly visits will last about 1.5-2.5 hours and consist of a breathalyzer/saliva test, self-report questionnaires 
about alcohol/drug use, PTSD and mood, and an individual therapy session. Telehealth participants will be 
required to complete the saliva alcohol test in front of the camera (test strip held on tongue for ten seconds) 
which will allow a study team member to assess and validate test results. During the treatment phase you will 
complete 8 therapy sessions. These therapy sessions will involve helping you identify and change unhelpful 
thoughts and behaviors related to alcohol/drug use.  The therapy in this research study will be in individual 
format and will be conducted by a well-trained clinician working under the supervision of project investigators 
who are clinical psychologists and medical doctors. 
At the end of the medication phase (week 8), you will stop taking the study medication.  No additional study 
medication will be given.  


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 4 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
Follow-up Phase  
You will be asked to return to the clinic or meet via telehealth about 1 and 3 months after the medication phase 
for questionnaires, assessment of substance use and PTSD symptoms, and alcohol breathalyzer/saliva tests and 
urine tests. You will not receive study medication during the follow-up phase.  You will also be asked to report 
any side effects, such as dizziness and headaches, you may have had since your last clinic visit. If you cannot be 
reached directly for this follow-up visit, attempts will be made to reach you by contacting people identified by 
you in your locator form. This will only be done to verify your physical well-being and safety. 
 
Neuroimaging Portion of the Study  
If you choose to participate in the neuroimaging (i.e., brain scan) portion of the study, you will be asked a series 
of questions regarding the presence of metallic items in or on your body and about any brain injuries. If you are 
eligible to participate in the scanning session, you will be scheduled for 2 magnetic resonance imaging (MRI) 
scanning sessions – the first will be before you begin taking the study medication and the second will be during 
the final week (week 8) of taking the study medication. You will be asked to meet the study personnel at the 
Center for Biomedical Imaging (CBI) at 30 Bee Street, which is on the MUSC campus, for the neuroimaging 
visits.    
 
The neuroimaging sessions will last approximately 1.5 hours each. When you arrive, you will be asked the same 
series of questions regarding the presence of metallic items in your body. If you are female you will also be 
asked to provide a urine sample for a pregnancy test. If you are pregnant, or if there are any metallic items in 
your body that prevent safe MRI scanning, you will not be eligible to participate further in the MRI portion of 
this investigation.  
 
The MRI is a large doughnut shaped machine. You will be given earplugs to wear while you are in the scanner. 
You will be able to speak to and hear the research staff during the scan.  We will first ask you to lay still and 
close your eyes while we take images of the structure of your brain. Following the structural images, we will 
acquire functional images of your brain activity while you listen to recordings describing your recent 
experiences with alcohol/drug, trauma and neutral cues.  The same procedures will be followed during the first 
and the second scanning visits.   


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 5 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
If you are 21-40 years old, please initial by your choice below:  
 
____ Yes, I would like to participate in the neuroimaging visits.  
 
____ No, I do not want to participate in the neuroimaging visits.  
 
____ N/A, I am not between the ages of 21-40. 
 
C.  Duration 
The total time in the study will be approximately 22 weeks consisting of:  
1) The screening and baseline phase takes 1 to 2 weeks. You will be asked to come in for up to 3 visits 
during this phase with the first visit lasting about 3 to 4 hours (assessment to determine eligibility to 
participate in the study), the second lasting about 1.5 hours (neuroimaging scan) and the third visit 
(medication start) lasting about 1 hour.  
 
2) The medication phase will last 8 weeks. During this phase, you will be asked to come to the clinic or 
meet via telehealth once a week for visits lasting about 1.5-2.5 hours.  The longer visit during week 4 
and week 8 will take about 2.5 hours because of additional questionnaires during those visits and require 
coming into the clinic. The final neuroimaging scan will take place during week 8 of the treatment phase 
and will last about 1.5 hours.  
 
3) The follow-up phase involves visits at 1 and 3 months after you stop taking the medication. These visits 
should take about 1.5 to 2 hours to complete. 
 
D. Possible Discomforts and/or Risks 
You will have to take time to come to the clinic or meet via telehealth during the screening, medication and 
follow-up phases of the study. Therefore, being in this study may cause inconvenience in your schedule at times.  
Some of the questions about your personal life, substance use, or PTSD symptoms may embarrass you or cause 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 6 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
you distress or boredom.  
You may have some side effects from the study medication.  The side effects most common in people who take 
NAC by mouth include diarrhea, nausea and vomiting, and headache.  These side effects are usually mild and go 
away even with continued use of NAC by mouth.  In this study, NAC will only be given by mouth. In addition 
to the side effects listed above, a skin rash has happened in about 10% of subjects participating in previous 
studies. If you develop a rash, you will be removed from the study medication and will be looked at by a study 
physician. You may, if necessary, be treated with an antihistamine (example: Benadryl) or another medication to 
help out with the rash.   
It is highly unlikely (probably less than one chance in several thousand) that you will have a severe allergic 
reaction to the NAC. If you have trouble breathing, the emergency medical system (EMS - call 911) should be 
called, and you should be transported to the nearest emergency room for immediate treatment.  Because NAC 
has not been studied in combination with very many other medications, it will be important for you to report to 
the research staff any medications you may be taking before, during, or after the medication phase.  Medications 
include prescription medications from a doctor, over-the-counter medications that you may buy in a drug store, 
herbal medications that you may buy in a health-food store, or “street” drugs. 
There are known psychological risks associated with withdrawal from many substances of abuse including 
increased sleepiness, unhappy mood, craving, and irritability.   
You will be asked to answer questions about your substance use, legal history and lifestyle.  The risk of release 
of this sensitive, confidential information will be kept to a minimum by storing your information in locked 
cabinets that are in locked offices.  The research staff that will be working with you has been thoroughly trained 
to keep your information confidential.  
There is a chance that you will receive a placebo pill (a pill without medication) instead of the study medication.  
There is a chance that NAC or placebo may not reduce your desire to use alcohol/drugs or your PTSD 
symptoms.  There is also a chance that your alcohol/drug use or PTSD symptoms may worsen while you are in 
this study.  The research or procedures may involve risks that are currently unforeseeable but your health will be 
monitored closely to minimize the possibility of side effects. 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 7 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
The safety of NAC in pregnancy and in nursing mothers is unknown.  Therefore, all women will be given a 
urine pregnancy test during screening and monthly during the medication phase.  No pregnant women or nursing 
mothers may be in this study.  Women must use a medically acceptable form of birth control while participating 
in the study.  Acceptable forms of birth control are: an oral contraceptive (birth control pills), diaphragm or a 
condom used with a spermicide, intrauterine progestive contraceptive system (Progestacert®), levonorgestrel 
implant (Norplant®), medroxyprogesterone (Depoprovera®) injection contraception, surgical sterilization, or 
complete abstinence from sexual intercourse during the entire study. If you become pregnant during the study, 
you will be taken off the study medication and your participation in the study must end. If you wish, you will be 
referred for regular clinical treatment.  If you become pregnant and test positive for illegal drugs, it is a law that 
the South Carolina Department of Social Services (DSS) must be notified.  You and your family will be 
evaluated by the agency.  You could be ordered to mandatory drug treatment, lose custody of your children, or 
possibly be jailed. 
Potential risks of Neuroimaging: 
The risk from MRI is low. No radiation or x-rays are used in making pictures of your brain during the MRIs. 
You cannot have an MRI scan if you have metal in the skull, metal implants, a cardiac or brain pacemaker, or 
old metal fragments in the eye or retina.  If you have a question about metal in your body, you should inform the 
researchers and they will determine whether it is safe in an MRI scanner.  Some discomfort may occur from 
having to remain still for a while in the scanner.  There is no exposure to ionizing radiation, nothing will be 
injured, and no blood will be taken. The MRI scanner is noisy, and there is a risk of hearing damage if you do 
not wear earplugs. To eliminate this risk, you will be given earplugs to wear during each scan.  
Although the MRI scanner is open on both ends, some people become anxious when entering the MRI scanner 
due to the feeling of being enclosed. If this has happened to you in the past, you should inform the study 
personnel. To address this concern, all participants will be given an emergency call button which they can 
activate at any time during the scan if they are feeling uncomfortable in the MRI scanner. If this indicator is 
activated the study personnel will come into the scanning room immediately and take you out of the MRI.   
 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 8 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
E. Possible Benefits 
There are no guarantees that you will directly benefit from taking part in the study. Based on experience with 
NAC and cognitive behavioral therapy in patients with similar disorders, researchers believe it may be of benefit 
to people with your conditions. Of course, because people respond differently to medications and behavioral 
therapies, no one can know in advance if it will be helpful for you.  Being in this research study may reduce 
your alcohol/drug use and PTSD symptoms, and it may also help in the understanding of how safe and effective 
NAC is in treating these conditions. Another benefit is that the information gained from the study will help 
increase our knowledge about how to best treat Veterans with PTSD and substance use disorder. 
 
F. Cost of Participation 
You will not be required to pay for medical care or services received as a participant in a VA research project 
except as follows: Some veterans are required to pay co-payments for medical care and services provided by 
VA.  These co-payment requirements will continue to apply to medical care and services provided by VA that 
are not part of this study.  
G.   Payment to Participants 
You will be compensated for providing data and for your time while in this research study. You will receive $50 
for the baseline visit, $50 for each imaging visit, and up to $40 for each weekly visit ($20 study visit, $20 
therapy session). You will also receive $75 for each follow-up visit at 1 and 3 months after treatment.  Thus, the 
total amount you may receive for your study participation is $755. Compensation can be provided by cash (in-
person pick up only), gift card (in-person pick up only), or check (requires mailing address and full social 
security number, may take 4-6 weeks to arrive). 
Telehealth participants will be offered compensation for travel to and from the three mandatory in-person visits 
(Baseline, Week 4, & Week 8). Also, if the baseline visit is four hours or longer, telehealth participants will be 
offered a meal. 
 
Referrals 
You are invited to participate in the recruitment of other subjects for this study.  If you choose to participate, we 
will provide you with cards that you may give to other people (e.g., friends, acquaintances) who you think 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 9 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
would be eligible and interested in this study.  You may choose to tell people to whom you give these cards to 
call the study office if they are interested in participating in the study.  These individuals will not be identified 
unless they contact the study office themselves.  If any of the cards you are given result in successful study 
recruitment, you will receive $10 for each referred individual who enrolls in the study. Participation in the 
recruitment process is completely voluntary and if you elect not to participate, your participation in this study 
will not be affected in any way. 
 
The Internal Revenue Service (IRS) requires a tax form be filed if your compensation exceeds $600/year. 
However, if the payment for participation will be made through Austin Financial Service Center, it may generate 
IRS Form 1099 automatically, regardless of amount. 
H. Alternatives 
If you do not want to be in this study, other ways of treating substance use problems and PTSD are individual or 
group counseling, as well as several FDA approved medications. If you would like, we will refer you to clinical 
treatment. You will be responsible for the costs of treatment. 
Withdrawal from the Study 
Your participation in this study is voluntary. You may refuse to take part in or stop taking part in this study at 
any time. You should talk with the investigator in charge of this study if you decide to do this. Your decision not 
to take part in the study will not affect your current or future medical care or any benefits to which you are 
entitled. The investigators and/or the sponsor may stop your participation in this study at any time if they decide 
it is in your best interest. They may also do this if you do not follow the investigator’s instructions. If your 
participation is ended for medical reasons, you will be referred to a doctor or other health professional for care. 
You will be responsible for the cost of these services. 
I. Disclosure Of Results 
You may request to receive a report of the aggregate results following completion of the study. 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 10 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
J. New Information  
If there are significant new findings during the course of the study, you will be notified. These new findings 
include, but are not limited to, changes in the potential risks or benefits resulting from being in the research or 
new alternatives to being in this study, which might cause you to change your mind about continuing in the 
study.  If new information is provided to you, your consent to continue taking part in this study will be re-
obtained.  
 
K. Release Of Medical Records To Anyone Other Than The Investigators 
If for any reason you would like your study records released to anyone other than the investigators, you will be 
asked to sign an additional release of information form. You will also be asked to sign a Health Insurance 
Portability and Accountability Act (HIPAA) Authorization to use or disclose your protected health information 
for research purposes.  
 
L. Student Participation 
Your participation or discontinuance will not constitute an element of your academic performance nor will it be 
part of your academic record.  
 
M. Employee Participation 
Your participation or discontinuance will not constitute an element of your job performance or evaluation nor 
will it be part of your employee record. 
 
N. Clinical Trial Registry Databank 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. 
This web site will not include information that can identify you. At most, the web site will include a summary of 
the results. You can search this web site at any time. 
 
 
 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 11 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
O. Contact 
You have the option of receiving appointment reminders and links to study surveys through text 
messages. Should you elect to receive text messages, normal cellular data usage and rates will apply. 
Please indicate your choice below: 
____Yes, I agree to be contacted via text message 
____No, I do not agree to be contacted via text message 
 
Confidentiality: 
We will take careful precautions to maintain your confidentiality, using procedures that we have successfully 
employed in similar previous as well as ongoing studies with Veterans. All study data related to psychological 
outcomes (i.e., the responses to questionnaires) and demographics will not have any unique identifying data 
attached in any way. There will be a master list of participants (again, not linked to any participant responses) 
which will be kept separate from all data and will be available only to Dr. Back and approved study personnel. 
All data will be stored in a confidential manner (i.e., in locked files or on encrypted computers in the Study 
Coordinator’s or Research Assistant’s office). Access to research records (paper and computerized) will be 
restricted to the project staff, sponsor audit personnel, VAMC R&D auditors, and MUSC IRB auditors. 
Neuroimaging data will be stored on a secure password protected server maintained by MUSC’s Center for 
Biomedical Imaging (CBI) for the purposes of this study. Only Dr. Back and approved study personnel will 
have access to the files on the secure CBI server.  
 
 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 12 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
CONSENT 
Results of this research will be used for the purposes described in this study. This information may be published, 
but you will not be identified. Information that is obtained concerning this research that can be identified with 
you will remain confidential to the extent possible within State and Federal law. The sponsor and the Food and 
Drug Administration (FDA) will receive copies of the research records. The investigators associated with this 
study, employees of the sponsor, the FDA, and the MUSC Institutional Review Board for Human Research will 
have access to identifying information. All records in South Carolina are subject to subpoena by a court of law. 
The VA will provide necessary medical treatment to a research subject injured by participation in a research 
project.  This requirement does not apply to treatment for injuries that result from non-compliance by a research 
subject with study procedures. If you sustain an injury as a direct result of your study participation, medical care 
will be provided by this VA Medical Center.  Financial compensation is not available for such things as lost 
wages, disability or discomfort due to an injury. 
Your participation in this study is voluntary. You may refuse to take part in or stop taking part in this study at 
any time. You should call the investigator in charge of this study if you decide to do this. The data collected on 
you to this point remains part of the study database and may not be removed. Your decision not to take part in 
the study will not affect your current or future medical care or any benefits to which you are entitled. 
 
 
 
 
 


 
Department of Veterans Affairs 
VAMC CHARLESTON 
VA Research Consent Form 
(Page 13 of 13 ) 
Subject’s Name: 
                                                                  Date: 
Principal Investigator: 
Sudie E. Back, Ph.D. 
Study Title:  
Glial Regulators for Treating Comorbid Posttraumatic Stress Disorder and 
Substance Use Disorders 
 
 
 
 
 
 
 
VA FORM 
                                 10-1086 
JAN 1990 
                                             
2.2.16 VAMC CHARLESTON   Form Version March 27, 2014 
 
  
V4.15.19 
 
 
 
IRB Number: Pro00052757 
Date Approved 4/26/2019 
 
Volunteers Statement 
I have been given a chance to ask questions about this research study. These questions have been answered to 
my satisfaction. If I have any more questions about my participation in this study or study related injury, or if I 
have comments, concerns or complaints I may contact Dr. Sudie Back at (843) 792-9383. I may contact the VA 
Medical Center’s Medical Director at (843) 789-7200 concerning medical treatment. 
If I have questions, comments, concerns or wish to voice a complaint, I may contact the VA Research 
Compliance Officer at (843) 789-7399.  
 
If I have any questions about my rights as a research subject in this study I may contact the Medical University 
of SC Institutional Review Board for Human Research at (843) 792-4148. 
 
I agree to participate in this study. I have been given a copy of this form for my own records. 
If you wish to participate, you should sign below. 
                                                                                
                                                                       
Signature of Person Obtaining Consent     Date 
Signature of Participant 
    Date