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Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)

Primary Purpose

Post Traumatic Stress Disorder (PTSD), Addiction, Alcohol Abuse

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
N-Acetylcysteine (NAC) Treatment
Cognitive Behavioral Therapy (CBT)
Inactive Placebo Oral Capsule
Functional magnetic resonance imaging (fMRI)
Proton magnetic resonance spectroscopy (MRS) Imaging
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Post Traumatic Stress Disorder (PTSD) focused on measuring Post Traumatic Stress Disorder (PTSD), Addiction, Alcohol Use Disorder, Cognitive Behavioral Therapy, N-acetylcysteine (NAC)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Male or female; any race or ethnicity; age 18 to 70 years old.
  2. Subjects must be able to comprehend English.
  3. Meet DSM-5 criteria for current alcohol use disorder (AUD).
  4. Meet DSM-5 criteria for current PTSD or subthreshold PTSD. Subjects may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or other anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder). The inclusion of subjects with affective and other anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with AUD and PTSD (Brady et al., 2000; Kessler et al., 2005). Subjects may meet DSM-5 criteria for another substance use disorder as long as AUD is the primary substance of choice.
  5. Subjects taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before treatment initiation. This is because initiation or change of medications during the course of the trial may interfere with interpretation of results.
  6. Must consent to random assignment to N-acetylcysteine (NAC) or placebo.
  7. Must consent to complete all treatment and follow-up visits.
  8. Must live within 50 miles (one hour) of MUSC in Charleston, SC or be willing to travel to MUSC for visits.

Exclusion Criteria:

  1. Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, as the study protocol may be therapeutically insufficient.
  2. Subjects with a current eating disorder (bulimia, anorexia nervosa) or with dissociative identity disorder, as they are likely to require specific time-intensive psychotherapy.
  3. Subjects experiencing significant withdrawal symptoms, as evidence by a score of 10 or above on the Clinical Institute Withdrawal Assessment of Alcohol (CIWA). These subjects will be referred for clinical detoxification and may be re-assessed for study eligibility after medically supervised detoxification has been completed.
  4. Individuals considered an immediate suicide risk or who are likely to require hospitalization during the course of the study for suicidality.

    Women who are pregnant, nursing or not practicing an effective form of birth control.

  5. Evidence of liver failure; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 3 times the upper limit of normal; asthma or any clinically significant medical condition that in the opinion of the investigator would adversely affect safety or study participation.
  6. Use of carbamazepine, phenytoin, nitrous oxide, methotrexate, 6 azauridine triacetate, or nitroglycerin within the last 14 days or any other medication felt to have a hazardous interaction if taken with NAC.
  7. History of childhood or adult seizures of any cause.

Sites / Locations

  • Medical University of South Carolina
  • The Charleston Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

N-Acetylcysteine (NAC) Treatment Group

Placebo Group

Arm Description

Participant will receive 12 weeks of Active Treatment NAC (2400 mg) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring. Participant will receive one week of study medication at a time from the study physician or the study coordinator. The study medication provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Participant will receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring. Participant will receive one week of study medication (placebo) at a time from the study physician or the study coordinator. The study medication (placebo) provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.

Outcomes

Primary Outcome Measures

Change in Alcohol Use Severity
Change in Alcohol Use Severity as measured by standard drinks per day using the Time Line Follow Back (TLFB) to measure alcohol consumption. Fewer standard drinks per day represent better outcomes. Greater change in standard drinks per day represents better outcomes.
Change in Alcohol Craving - Obsessive Subscale
Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the obsessive subscale of alcohol craving. The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Obsessive subscale includes items 1-6. Each item is scored on a scale from 0 to 4. Scores range from 0 to 28, with lower scores representing better outcomes.
Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated
Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered PTSD Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms. The CAPS-5 is a 30-item structured interview. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 PTSD symptoms, each with severity scores ranging from 0-4. The overall total severity score for CAPS-5 ranges from 0-80, with lower scores representing better outcomes (less severe PTSD).
Change in Post Traumatic Stress Disorder Symptom Severity - Self Report
Change in Post Traumatic Stress Disorder (PTSD) symptom severity as measured by the Posttraumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5](PCL-5) for self-reported symptoms. The PCL-5 is a 20-item self-report measure that assesses the 20 symptoms of PTSD. The rating scale is 0-4 for each symptom/item, and overall scores range from 0-80, with lower scores representing better outcomes (less severe PTSD).
Change in Alcohol Craving - Compulsive Subscale
Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the compulsive subscale of alcohol craving. The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Compulsive subscale includes items 7-14. Each item is scored on a scale from 0 to 4. Scores range from 0 to 32, with lower scores representing better outcomes.
Change in Alcohol Use Severity - Percent Days Abstinent
Change in Alcohol Use Severity as measured by the percent days abstinent using the Time Line Follow Back (TLFB) to measure alcohol consumption. Greater percentage of days of abstinence represents better outcomes. Greater change in Percent Days Abstinent represents better outcomes.

Secondary Outcome Measures

Full Information

First Posted
November 4, 2016
Last Updated
April 17, 2023
Sponsor
Medical University of South Carolina
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT02966873
Brief Title
Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)
Official Title
A Randomized Controlled Trial of N-Acetylcysteine for Alcohol Use Disorder and Comorbid Post Traumatic Stress Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
October 1, 2016 (Actual)
Primary Completion Date
September 16, 2021 (Actual)
Study Completion Date
September 19, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of South Carolina
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a randomized controlled Phase II clinical trial designed to evaluate the effects of N-acetylcysteine (NAC) in reducing Alcohol Use Disorder (AUD) severity and Post Traumatic Stress Disorder (PTSD) symptomatology among individuals with current AUD and PTSD.
Detailed Description
The primary objective of the proposed Phase II study is to evaluate the effects of N-acetylcysteine (NAC), in reducing (1) Alcohol Use Disorder (AUD) severity and (2) Post Traumatic Stress Disorder (PTSD) symptomatology among individuals (N=200) with current AUD and PTSD. We will also use functional magnetic resonance imaging (fMRI) and proton magnetic resonance spectroscopy (MRS) to investigate the neural circuitry and neurochemistry underlying comorbid AUD/PTSD and prognostic indicators of positive treatment response. Secondary objectives are to evaluate the effects of NAC on impairment in associated areas of functioning (e.g., depression, anxiety, sleep, risky behaviors). In order to accomplish this we will (1) employ an intent-to-treat, double-blind, placebo-controlled randomized controlled trial that will consist of 12 weeks of treatment with NAC (2400 mg per day) or placebo medication; (2) examine standardized, repeated dependent measures of clinical outcomes at baseline, week 6, week 12, and 3-, 6-, and 12-month follow-up; and (3) employ advanced neuroimaging methodologies, a laboratory cue paradigm, and collect biologic measures of alcohol consumption. All participants will also undergo weekly individual cognitive behavior therapy sessions (CBT).The following specific aims are proposed: Specific Aim 1: To determine the efficacy of N-acetylcysteine (NAC), as compared to placebo, in reducing alcohol use severity (i.e., total standard drinks, percent days drinking, abstinence rates) and craving. Specific Aim 2: To determine the efficacy of N-acetylcysteine (NAC), as compared to placebo, in reducing self-report and clinician-rated PTSD symptomatology. Specific Aim 3: To use multimodal neuroimaging techniques to investigate the pathophysiology underlying AUD and comorbid PTSD, and prognostic indicators of treatment outcome. The proposed study will answer critical questions regarding the potential of NAC as an effective pharmacotherapy for AUD and comorbid PTSD, and elucidate possible mechanisms underlying improved outcomes. This study has the particular advantage of building directly on positive preliminary findings by (1) further testing NAC in the treatment of individuals with co-occurring AUD/PTSD using a double-blind, placebo-controlled randomized design; (2) measuring functioning in related areas, such as depression and risky behaviors; (3) employing innovative measurements including neuroimaging and laboratory cue paradigms; and (4) employing a multidisciplinary team of experts who have successfully collaborated in the past and are uniquely qualified to implement this type of investigation. This project is directly responsive to the mission of the National Institute of Alcohol and Alcoholism (NIAAA) and the new AUD/PTSD initiative in that it seeks to evaluate a promising therapeutic agent for the treatment of AUD/PTSD and identify neurobiological mechanisms common to AUD/PTSD as potential treatment targets. The findings from this study have the potential to significantly improve the standard of patient care, advance the comorbidity science in this area, and decrease public health expenditures associated with AUD and comorbid PTSD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Traumatic Stress Disorder (PTSD), Addiction, Alcohol Abuse
Keywords
Post Traumatic Stress Disorder (PTSD), Addiction, Alcohol Use Disorder, Cognitive Behavioral Therapy, N-acetylcysteine (NAC)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
182 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N-Acetylcysteine (NAC) Treatment Group
Arm Type
Experimental
Arm Description
Participant will receive 12 weeks of Active Treatment NAC (2400 mg) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring. Participant will receive one week of study medication at a time from the study physician or the study coordinator. The study medication provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Participant will receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring. Participant will receive one week of study medication (placebo) at a time from the study physician or the study coordinator. The study medication (placebo) provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.
Intervention Type
Drug
Intervention Name(s)
N-Acetylcysteine (NAC) Treatment
Intervention Description
Participant will receive 12 weeks of Active Treatment NAC (2400 mg) daily. The study medication will be provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.
Intervention Type
Behavioral
Intervention Name(s)
Cognitive Behavioral Therapy (CBT)
Intervention Description
Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.
Intervention Type
Drug
Intervention Name(s)
Inactive Placebo Oral Capsule
Intervention Description
Participant will receive 12 weeks of inactive placebo. The study medication will be provided in blister packs in the form of 600 mg tablets. Each participant will be asked to take two (2) 600 mg tablets in the morning and two (2) 600 mg tablets in the evening.
Intervention Type
Other
Intervention Name(s)
Functional magnetic resonance imaging (fMRI)
Other Intervention Name(s)
Imaging
Intervention Description
Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).
Intervention Type
Other
Intervention Name(s)
Proton magnetic resonance spectroscopy (MRS) Imaging
Intervention Description
Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).
Primary Outcome Measure Information:
Title
Change in Alcohol Use Severity
Description
Change in Alcohol Use Severity as measured by standard drinks per day using the Time Line Follow Back (TLFB) to measure alcohol consumption. Fewer standard drinks per day represent better outcomes. Greater change in standard drinks per day represents better outcomes.
Time Frame
From baseline to week 12
Title
Change in Alcohol Craving - Obsessive Subscale
Description
Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the obsessive subscale of alcohol craving. The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Obsessive subscale includes items 1-6. Each item is scored on a scale from 0 to 4. Scores range from 0 to 28, with lower scores representing better outcomes.
Time Frame
From baseline to week 12
Title
Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated
Description
Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered PTSD Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms. The CAPS-5 is a 30-item structured interview. CAPS-5 total symptom severity score is calculated by summing severity scores for the 20 PTSD symptoms, each with severity scores ranging from 0-4. The overall total severity score for CAPS-5 ranges from 0-80, with lower scores representing better outcomes (less severe PTSD).
Time Frame
From baseline to week 12
Title
Change in Post Traumatic Stress Disorder Symptom Severity - Self Report
Description
Change in Post Traumatic Stress Disorder (PTSD) symptom severity as measured by the Posttraumatic Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition [DSM-5](PCL-5) for self-reported symptoms. The PCL-5 is a 20-item self-report measure that assesses the 20 symptoms of PTSD. The rating scale is 0-4 for each symptom/item, and overall scores range from 0-80, with lower scores representing better outcomes (less severe PTSD).
Time Frame
From baseline to week 12
Title
Change in Alcohol Craving - Compulsive Subscale
Description
Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the compulsive subscale of alcohol craving. The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Compulsive subscale includes items 7-14. Each item is scored on a scale from 0 to 4. Scores range from 0 to 32, with lower scores representing better outcomes.
Time Frame
From baseline to week 12
Title
Change in Alcohol Use Severity - Percent Days Abstinent
Description
Change in Alcohol Use Severity as measured by the percent days abstinent using the Time Line Follow Back (TLFB) to measure alcohol consumption. Greater percentage of days of abstinence represents better outcomes. Greater change in Percent Days Abstinent represents better outcomes.
Time Frame
From baseline to week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Male or female; any race or ethnicity; age 18 to 70 years old. Subjects must be able to comprehend English. Meet DSM-5 criteria for current alcohol use disorder (AUD). Meet DSM-5 criteria for current PTSD or subthreshold PTSD. Subjects may also meet criteria for a mood disorder (except bipolar affective disorder, see Exclusion Criteria) or other anxiety disorders (panic disorder, agoraphobia, social phobia, generalized anxiety disorder, or obsessive compulsive disorder). The inclusion of subjects with affective and other anxiety disorders is essential because of the marked frequency of the co-existence of mood and other anxiety disorders among patients with AUD and PTSD (Brady et al., 2000; Kessler et al., 2005). Subjects may meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for another substance use disorder as long as AUD is the primary substance of choice. Subjects taking psychotropic medications will be required to be maintained on a stable dose for at least four weeks before treatment initiation. This is because initiation or change of medications during the course of the trial may interfere with interpretation of results. Must consent to random assignment to N-acetylcysteine (NAC) or placebo. Must consent to complete all treatment and follow-up visits. Exclusion Criteria: Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar affective disorders, as the study protocol may be therapeutically insufficient. Subjects with a current eating disorder (bulimia, anorexia nervosa) or with dissociative identity disorder, as they are likely to require specific time-intensive psychotherapy. Subjects experiencing significant withdrawal symptoms, as evidence by a score of 10 or above on the Clinical Institute Withdrawal Assessment of Alcohol (CIWA). These subjects will be referred for clinical detoxification and may be re-assessed for study eligibility after medically supervised detoxification has been completed. Individuals considered an immediate suicide risk or who are likely to require hospitalization during the course of the study for suicidality. Women who are pregnant, nursing or not practicing an effective form of birth control. Evidence of liver failure; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 3 times the upper limit of normal; asthma or any clinically significant medical condition that in the opinion of the investigator would adversely affect safety or study participation. Use of carbamazepine, phenytoin, nitrous oxide, methotrexate, 6 azauridine triacetate, or nitroglycerin within the last 14 days or any other medication felt to have a hazardous interaction if taken with NAC. History of childhood or adult seizures of any cause.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudie Back, PhD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29401
Country
United States
Facility Name
The Charleston Center
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)

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