<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02966873</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00056889</org_study_id>
    <secondary_id>1R01AA025086</secondary_id>
    <nct_id>NCT02966873</nct_id>
  </id_info>
  <brief_title>Clinical Trial for Alcohol Use Disorder and Post Traumatic Stress Disorder (PTSD)</brief_title>
  <official_title>A Randomized Controlled Trial of N-Acetylcysteine for Alcohol Use Disorder and Comorbid Post Traumatic Stress Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized controlled Phase II clinical trial designed to evaluate the effects of&#xD;
      N-acetylcysteine (NAC) in reducing Alcohol Use Disorder (AUD) severity and Post Traumatic&#xD;
      Stress Disorder (PTSD) symptomatology among individuals with current AUD and PTSD.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of the proposed Phase II study is to evaluate the effects of&#xD;
      N-acetylcysteine (NAC), in reducing (1) Alcohol Use Disorder (AUD) severity and (2) Post&#xD;
      Traumatic Stress Disorder (PTSD) symptomatology among individuals (N=200) with current AUD&#xD;
      and PTSD. We will also use functional magnetic resonance imaging (fMRI) and proton magnetic&#xD;
      resonance spectroscopy (MRS) to investigate the neural circuitry and neurochemistry&#xD;
      underlying comorbid AUD/PTSD and prognostic indicators of positive treatment response.&#xD;
      Secondary objectives are to evaluate the effects of NAC on impairment in associated areas of&#xD;
      functioning (e.g., depression, anxiety, sleep, risky behaviors). In order to accomplish this&#xD;
      we will (1) employ an intent-to-treat, double-blind, placebo-controlled randomized controlled&#xD;
      trial that will consist of 12 weeks of treatment with NAC (2400 mg per day) or placebo&#xD;
      medication; (2) examine standardized, repeated dependent measures of clinical outcomes at&#xD;
      baseline, week 6, week 12, and 3-, 6-, and 12-month follow-up; and (3) employ advanced&#xD;
      neuroimaging methodologies, a laboratory cue paradigm, and collect biologic measures of&#xD;
      alcohol consumption. All participants will also undergo weekly individual cognitive behavior&#xD;
      therapy sessions (CBT).The following specific aims are proposed:&#xD;
&#xD;
      Specific Aim 1: To determine the efficacy of N-acetylcysteine (NAC), as compared to placebo,&#xD;
      in reducing alcohol use severity (i.e., total standard drinks, percent days drinking,&#xD;
      abstinence rates) and craving.&#xD;
&#xD;
      Specific Aim 2: To determine the efficacy of N-acetylcysteine (NAC), as compared to placebo,&#xD;
      in reducing self-report and clinician-rated PTSD symptomatology.&#xD;
&#xD;
      Specific Aim 3: To use multimodal neuroimaging techniques to investigate the pathophysiology&#xD;
      underlying AUD and comorbid PTSD, and prognostic indicators of treatment outcome.&#xD;
&#xD;
      The proposed study will answer critical questions regarding the potential of NAC as an&#xD;
      effective pharmacotherapy for AUD and comorbid PTSD, and elucidate possible mechanisms&#xD;
      underlying improved outcomes. This study has the particular advantage of building directly on&#xD;
      positive preliminary findings by (1) further testing NAC in the treatment of individuals with&#xD;
      co-occurring AUD/PTSD using a double-blind, placebo-controlled randomized design; (2)&#xD;
      measuring functioning in related areas, such as depression and risky behaviors; (3) employing&#xD;
      innovative measurements including neuroimaging and laboratory cue paradigms; and (4)&#xD;
      employing a multidisciplinary team of experts who have successfully collaborated in the past&#xD;
      and are uniquely qualified to implement this type of investigation. This project is directly&#xD;
      responsive to the mission of the National Institute of Alcohol and Alcoholism (NIAAA) and the&#xD;
      new AUD/PTSD initiative in that it seeks to evaluate a promising therapeutic agent for the&#xD;
      treatment of AUD/PTSD and identify neurobiological mechanisms common to AUD/PTSD as potential&#xD;
      treatment targets. The findings from this study have the potential to significantly improve&#xD;
      the standard of patient care, advance the comorbidity science in this area, and decrease&#xD;
      public health expenditures associated with AUD and comorbid PTSD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">September 19, 2022</completion_date>
  <primary_completion_date type="Actual">September 16, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Alcohol Use Severity</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>Change in Alcohol Use Severity as measured by standard drinks per day using the Time Line Follow Back (TLFB) to measure alcohol consumption.&#xD;
Fewer standard drinks per day represent better outcomes. Greater change in standard drinks per day represents better outcomes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Alcohol Craving - Obsessive Subscale</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the obsessive subscale of alcohol craving.&#xD;
The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Obsessive subscale includes items 1-6.&#xD;
Each item is scored on a scale from 0 to 4. Scores range from 0 to 28, with lower scores representing better outcomes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered PTSD Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms.&#xD;
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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Post Traumatic Stress Disorder Symptom Severity - Self Report</measure>
    <time_frame>From baseline to week 12</time_frame>
    <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.&#xD;
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).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Alcohol Craving - Compulsive Subscale</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the compulsive subscale of alcohol craving.&#xD;
The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Compulsive subscale includes items 7-14.&#xD;
Each item is scored on a scale from 0 to 4. Scores range from 0 to 32, with lower scores representing better outcomes.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Alcohol Use Severity - Percent Days Abstinent</measure>
    <time_frame>From baseline to week 12</time_frame>
    <description>Change in Alcohol Use Severity as measured by the percent days abstinent using the Time Line Follow Back (TLFB) to measure alcohol consumption.&#xD;
Greater percentage of days of abstinence represents better outcomes. Greater change in Percent Days Abstinent represents better outcomes.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">182</enrollment>
  <condition>Post Traumatic Stress Disorder (PTSD)</condition>
  <condition>Addiction</condition>
  <condition>Alcohol Abuse</condition>
  <arm_group>
    <arm_group_label>N-Acetylcysteine (NAC) Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.&#xD;
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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo Group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <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.&#xD;
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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-Acetylcysteine (NAC) Treatment</intervention_name>
    <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.</description>
    <arm_group_label>N-Acetylcysteine (NAC) Treatment Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive Behavioral Therapy (CBT)</intervention_name>
    <description>Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
    <arm_group_label>N-Acetylcysteine (NAC) Treatment Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Inactive Placebo Oral Capsule</intervention_name>
    <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.</description>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Functional magnetic resonance imaging (fMRI)</intervention_name>
    <description>Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).</description>
    <arm_group_label>N-Acetylcysteine (NAC) Treatment Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
    <other_name>Imaging</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Proton magnetic resonance spectroscopy (MRS) Imaging</intervention_name>
    <description>Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).</description>
    <arm_group_label>N-Acetylcysteine (NAC) Treatment Group</arm_group_label>
    <arm_group_label>Placebo Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female; any race or ethnicity; age 18 to 70 years old.&#xD;
&#xD;
          2. Subjects must be able to comprehend English.&#xD;
&#xD;
          3. Meet DSM-5 criteria for current alcohol use disorder (AUD).&#xD;
&#xD;
          4. Meet DSM-5 criteria for current PTSD or subthreshold PTSD. Subjects may also meet&#xD;
             criteria for a mood disorder (except bipolar affective disorder, see Exclusion&#xD;
             Criteria) or other anxiety disorders (panic disorder, agoraphobia, social phobia,&#xD;
             generalized anxiety disorder, or obsessive compulsive disorder). The inclusion of&#xD;
             subjects with affective and other anxiety disorders is essential because of the marked&#xD;
             frequency of the co-existence of mood and other anxiety disorders among patients with&#xD;
             AUD and PTSD (Brady et al., 2000; Kessler et al., 2005). Subjects may meet Diagnostic&#xD;
             and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for another&#xD;
             substance use disorder as long as AUD is the primary substance of choice.&#xD;
&#xD;
          5. Subjects taking psychotropic medications will be required to be maintained on a stable&#xD;
             dose for at least four weeks before treatment initiation. This is because initiation&#xD;
             or change of medications during the course of the trial may interfere with&#xD;
             interpretation of results.&#xD;
&#xD;
          6. Must consent to random assignment to N-acetylcysteine (NAC) or placebo.&#xD;
&#xD;
          7. Must consent to complete all treatment and follow-up visits.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects meeting DSM-5 criteria for a history of or current psychotic or bipolar&#xD;
             affective disorders, as the study protocol may be therapeutically insufficient.&#xD;
&#xD;
          2. Subjects with a current eating disorder (bulimia, anorexia nervosa) or with&#xD;
             dissociative identity disorder, as they are likely to require specific time-intensive&#xD;
             psychotherapy.&#xD;
&#xD;
          3. Subjects experiencing significant withdrawal symptoms, as evidence by a score of 10 or&#xD;
             above on the Clinical Institute Withdrawal Assessment of Alcohol (CIWA). These&#xD;
             subjects will be referred for clinical detoxification and may be re-assessed for study&#xD;
             eligibility after medically supervised detoxification has been completed.&#xD;
&#xD;
          4. Individuals considered an immediate suicide risk or who are likely to require&#xD;
             hospitalization during the course of the study for suicidality.&#xD;
&#xD;
             Women who are pregnant, nursing or not practicing an effective form of birth control.&#xD;
&#xD;
          5. Evidence of liver failure; alanine aminotransferase (ALT) or aspartate&#xD;
             aminotransferase (AST) levels greater than 3 times the upper limit of normal; asthma&#xD;
             or any clinically significant medical condition that in the opinion of the&#xD;
             investigator would adversely affect safety or study participation.&#xD;
&#xD;
          6. Use of carbamazepine, phenytoin, nitrous oxide, methotrexate, 6 azauridine triacetate,&#xD;
             or nitroglycerin within the last 14 days or any other medication felt to have a&#xD;
             hazardous interaction if taken with NAC.&#xD;
&#xD;
          7. History of childhood or adult seizures of any cause.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sudie Back, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Charleston Center</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>November 4, 2016</study_first_submitted>
  <study_first_submitted_qc>November 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 17, 2016</study_first_posted>
  <results_first_submitted>December 22, 2022</results_first_submitted>
  <results_first_submitted_qc>April 17, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 18, 2023</results_first_posted>
  <disposition_first_submitted>September 16, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>September 22, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 7, 2022</disposition_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of South Carolina</investigator_affiliation>
    <investigator_full_name>Elizabeth Santa Ana</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Post Traumatic Stress Disorder (PTSD)</keyword>
  <keyword>Addiction</keyword>
  <keyword>Alcohol Use Disorder</keyword>
  <keyword>Cognitive Behavioral Therapy</keyword>
  <keyword>N-acetylcysteine (NAC)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Stress Disorders, Traumatic</mesh_term>
    <mesh_term>Behavior, Addictive</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
    <mesh_term>Stress Disorders, Post-Traumatic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT02966873/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 6, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT02966873/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment for this project was ongoing from June 2016 through June 2021. Prior to the Coronavirus pandemic, recruitment efforts were focused in Charleston, South Carolina (clinics, online, community). In 2020, the study team shifted to a full remote approach and opened recruitment across the continental United States.</recruitment_details>
      <pre_assignment_details>Participants were stratified by alcohol use disorder severity and posttraumatic stress disorder severity. Stratified random block randomization was used to balance the randomization assignment with respect to these strata. The purpose of stratification is to distribute these potential prognostic factors equally across treatment groups.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>N-Acetylcysteine (NAC) Treatment Group</title>
          <description>Participant will receive 12 weeks of Active Treatment N-Acetylcysteine (NAC) (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Group</title>
          <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="93"/>
                <participants group_id="P2" count="89"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="77">N=77 represents 77 participants who provided at least one data point at week 12.</participants>
                <participants group_id="P2" count="74">N=74 represents 74 participants who provided at least one data point at week 12.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>N-Acetylcysteine (NAC) Treatment Group</title>
          <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
        </group>
        <group group_id="B2">
          <title>Placebo Group</title>
          <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="93"/>
            <count group_id="B2" value="89"/>
            <count group_id="B3" value="182"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.9" spread="13.2"/>
                    <measurement group_id="B2" value="39.7" spread="12.4"/>
                    <measurement group_id="B3" value="40.3" spread="12.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="57"/>
                    <measurement group_id="B2" value="56"/>
                    <measurement group_id="B3" value="113"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="72"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="138"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Ethnicity, % Hispanic</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Alcohol Use Severity</title>
        <description>Change in Alcohol Use Severity as measured by standard drinks per day using the Time Line Follow Back (TLFB) to measure alcohol consumption.&#xD;
Fewer standard drinks per day represent better outcomes. Greater change in standard drinks per day represents better outcomes.</description>
        <time_frame>From baseline to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-Acetylcysteine (NAC) Treatment Group</title>
            <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Use Severity</title>
          <description>Change in Alcohol Use Severity as measured by standard drinks per day using the Time Line Follow Back (TLFB) to measure alcohol consumption.&#xD;
Fewer standard drinks per day represent better outcomes. Greater change in standard drinks per day represents better outcomes.</description>
          <units>standard drinks per day</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.406" spread="3.738"/>
                    <measurement group_id="O2" value="-3.934" spread=".825"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Alcohol Craving - Obsessive Subscale</title>
        <description>Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the obsessive subscale of alcohol craving.&#xD;
The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Obsessive subscale includes items 1-6.&#xD;
Each item is scored on a scale from 0 to 4. Scores range from 0 to 28, with lower scores representing better outcomes.</description>
        <time_frame>From baseline to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-Acetylcysteine (NAC) Treatment Group</title>
            <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Craving - Obsessive Subscale</title>
          <description>Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the obsessive subscale of alcohol craving.&#xD;
The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Obsessive subscale includes items 1-6.&#xD;
Each item is scored on a scale from 0 to 4. Scores range from 0 to 28, with lower scores representing better outcomes.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="77"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.597" spread="4.314"/>
                    <measurement group_id="O2" value="-2.521" spread="3.738"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated</title>
        <description>Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered PTSD Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms.&#xD;
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).</description>
        <time_frame>From baseline to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-Acetylcysteine (NAC) Treatment Group</title>
            <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated</title>
          <description>Change in Post Traumatic Stress Disorder symptom severity as measured by Clinician Administered PTSD Scale (CAPS-5) for clinician-rated posttraumatic stress symptoms.&#xD;
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).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="74"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.838" spread="9.834"/>
                    <measurement group_id="O2" value="-13.863" spread="10.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Post Traumatic Stress Disorder Symptom Severity - Self Report</title>
        <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.&#xD;
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).</description>
        <time_frame>From baseline to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-Acetylcysteine (NAC) Treatment Group</title>
            <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Post Traumatic Stress Disorder Symptom Severity - Self Report</title>
          <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.&#xD;
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).</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.997" spread="18.907"/>
                    <measurement group_id="O2" value="-18.129" spread="18.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Alcohol Craving - Compulsive Subscale</title>
        <description>Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the compulsive subscale of alcohol craving.&#xD;
The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Compulsive subscale includes items 7-14.&#xD;
Each item is scored on a scale from 0 to 4. Scores range from 0 to 32, with lower scores representing better outcomes.</description>
        <time_frame>From baseline to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-Acetylcysteine (NAC) Treatment Group</title>
            <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Craving - Compulsive Subscale</title>
          <description>Change in Alcohol Craving as measured by the Obsessive Compulsive Drinking Scale (OCDS) to measure the compulsive subscale of alcohol craving.&#xD;
The OCDS is a 14-item questionnaire that measures alcohol use and attempts to control drinking. Compulsive subscale includes items 7-14.&#xD;
Each item is scored on a scale from 0 to 4. Scores range from 0 to 32, with lower scores representing better outcomes.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="77"/>
                <count group_id="O2" value="74"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.584" spread="3.971"/>
                    <measurement group_id="O2" value="-4.905" spread="4.266"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Alcohol Use Severity - Percent Days Abstinent</title>
        <description>Change in Alcohol Use Severity as measured by the percent days abstinent using the Time Line Follow Back (TLFB) to measure alcohol consumption.&#xD;
Greater percentage of days of abstinence represents better outcomes. Greater change in Percent Days Abstinent represents better outcomes.</description>
        <time_frame>From baseline to week 12</time_frame>
        <group_list>
          <group group_id="O1">
            <title>N-Acetylcysteine (NAC) Treatment Group</title>
            <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Group</title>
            <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Use Severity - Percent Days Abstinent</title>
          <description>Change in Alcohol Use Severity as measured by the percent days abstinent using the Time Line Follow Back (TLFB) to measure alcohol consumption.&#xD;
Greater percentage of days of abstinence represents better outcomes. Greater change in Percent Days Abstinent represents better outcomes.</description>
          <units>percentage of days abstinent for alcohol</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="75"/>
                <count group_id="O2" value="73"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.6" spread="35.2"/>
                    <measurement group_id="O2" value="31.7" spread="34.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Approximately 1 year and 3 months (from start of baseline appointment through 12 week treatment phase and 1 year follow up)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>N-Acetylcysteine (NAC) Treatment Group</title>
          <description>Participant will receive 12 weeks of Active Treatment NAC (2400 milligrams [mg]) daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Group</title>
          <description>Participants receive 12 weeks of inactive placebo comparator daily, as well as weekly cognitive-behavioral therapy, medication management, and Adverse Event (AE) monitoring.&#xD;
The study medication (placebo) provided in blister packs in the form of 600 milligrams [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.&#xD;
Cognitive Behavioral Therapy (CBT): All participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 10.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title vocab="Sepsis">Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury/Accident</sub_title>
                <description>Hospitalization from injury/accident.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title vocab="Stroke">Stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Ectopic Pregnancy</sub_title>
                <description>Hospitalization from ectopic pregnancy</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <description>Suicidal Ideation - Hospitalization</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title vocab="Pancreatitis">Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title vocab="Bladder Infection">Bladder Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Ruptured Fallopian Tube</sub_title>
                <description>Surgical procedure to repair ruptured fallopian tube (complication from ectopic pregnancy). Participant was hospitalized.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <description>Pneumonia - hospitalized</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 10.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="39" subjects_at_risk="93"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <description>Constipation</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Discomfort</sub_title>
                <description>Gastrointestinal Discomfort, non-specified</description>
                <counts group_id="E1" events="23" subjects_affected="18" subjects_at_risk="93"/>
                <counts group_id="E2" events="11" subjects_affected="9" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title vocab="Nausea">Nausea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="93"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <description>Flatulence</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="93"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <description>Sinusitis</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="93"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Viral Upper Respiratory Tract Infections (Cold)</sub_title>
                <description>Viral Upper Respiratory Tract Infections (Cold)</description>
                <counts group_id="E1" events="17" subjects_affected="15" subjects_at_risk="93"/>
                <counts group_id="E2" events="17" subjects_affected="14" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury</sub_title>
                <description>injury: abscess on hand wound post surgery Injury: back injury from work injury: broken toe (pinky, left foot) Injury: broken tooth injury: infection in hand post-surgery injury: knee injury injury: sprained ankle</description>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="93"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle or Joint Pain</sub_title>
                <description>Muscle or Joint Pain (neck, back, wrist, rib, side, led)</description>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="93"/>
                <counts group_id="E2" events="16" subjects_affected="11" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <description>Anxiety Anxiety or Panic Attack Anxiety, worsening</description>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="93"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Headache/Migraine</sub_title>
                <description>Headache (including worsening) Migraine(including worsening)</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="93"/>
                <counts group_id="E2" events="14" subjects_affected="13" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Stacey Sellers</name_or_title>
      <organization>Medical University of South Carolina</organization>
      <phone>843-792-5807</phone>
      <email>sellersst@musc.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02966873
org study id: Pro00056889
secondary id: 1R01AA025086
nct id: NCT02966873
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Alcohol Use Severity
time frame: From baseline to week 12
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.
measure: Change in Alcohol Craving - Obsessive Subscale
time frame: From baseline to week 12
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.
measure: Change in Post Traumatic Stress Disorder Symptom Severity - Clinician Rated
time frame: From baseline to week 12
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).
measure: Change in Post Traumatic Stress Disorder Symptom Severity - Self Report
time frame: From baseline to week 12
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).
measure: Change in Alcohol Craving - Compulsive Subscale
time frame: From baseline to week 12
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.
measure: Change in Alcohol Use Severity - Percent Days Abstinent
time frame: From baseline to week 12
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.
arm group label: N-Acetylcysteine (NAC) Treatment Group
arm group type: Experimental
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 group label: Placebo Group
arm group type: Placebo Comparator
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: N-Acetylcysteine (NAC) Treatment
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.
arm group label: N-Acetylcysteine (NAC) Treatment Group
intervention type: Behavioral
intervention name: Cognitive Behavioral Therapy (CBT)
description: Participant will receive 12 weeks of weekly cognitive-behavioral therapy, medication management, and AE monitoring.
arm group label: N-Acetylcysteine (NAC) Treatment Group
arm group label: Placebo Group
intervention type: Drug
intervention name: Inactive Placebo Oral Capsule
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.
arm group label: Placebo Group
intervention type: Other
intervention name: Functional magnetic resonance imaging (fMRI)
description: Participants will be given the option to complete Functional magnetic resonance imaging (fMRI) at two timepoints (pre-treatment and end of treatment).
arm group label: N-Acetylcysteine (NAC) Treatment Group
arm group label: Placebo Group
other name: Imaging
intervention type: Other
intervention name: Proton magnetic resonance spectroscopy (MRS) Imaging
description: Participants will be given the option to complete magnetic resonance spectroscopy (MRS) at two timepoints (pre-treatment and end of treatment).
arm group label: N-Acetylcysteine (NAC) Treatment Group
arm group label: Placebo Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sudie Back, PhD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical University of South Carolina
investigator full name: Elizabeth Santa Ana
investigator title: Principal Investigator
mesh term: Alcoholism
mesh term: Stress Disorders, Traumatic
mesh term: Behavior, Addictive
mesh term: Alcohol Drinking
mesh term: Stress Disorders, Post-Traumatic
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: Yes
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 