NAC: N-acetylcysteine Treatment of Alcohol Use Disorder In Veterans With TBI

Sponsor
University of California, San Francisco (Other)
Overall Status
Completed
CT.gov ID
NCT02791945
Collaborator
United States Department of Defense (U.S. Fed), Northern California Institute of Research and Education (Other), San Francisco Veterans Affairs Medical Center (U.S. Fed), Institute for Translational Neuroscience (Other)
30
1
2
21
1.4

Study Details

Study Description

Brief Summary

The goal of the project is to improve the care of Veterans with mild traumatic brain injury (mTBI) and unhealthy alcohol use.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a pilot controlled clinical trial that aims to assess the efficacy of N-acetylcysteine (NAC) to reduce alcohol use and improve brain injury symptoms in Veterans with mTBI who consume alcohol at hazardous or harmful levels.

Study Design

Study Type:
Interventional
Actual Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
N-acetylcysteine Treatment of Alcohol Use Disorder In Veterans With TBI
Study Start Date :
Aug 1, 2016
Actual Primary Completion Date :
May 1, 2018
Actual Study Completion Date :
May 1, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: N-acetylcysteine

N-acetylcysteine capsules daily - up to 3200 mg

Behavioral: Medical Management Counseling
Brief alcohol counseling

Drug: N-acetylcysteine
Experimental supplement
Other Names:
  • NAC
  • Placebo Comparator: Placebo

    Placebo capsules daily - up to 3200 mg

    Behavioral: Medical Management Counseling
    Brief alcohol counseling

    Drug: Placebo
    Placebo comparator

    Outcome Measures

    Primary Outcome Measures

    1. Change in Percent of Heavy Drinking Days Per Week as Assessed by the Timeline Followback (TFLB) [Baseline to Week 8]

      The TLFB interview, using a calendar, asks participants to report the prior week's frequency of alcohol use on each day of the week.

    2. Change in TBI Symptoms as Assessed by the Neurobehavioral Symptom Inventory (NSI) [Baseline to Week 8]

      Participants indicate the extent to which each of the 22 symptoms has disturbed them in the previous 2 weeks on a 5-item scale (0-none to 4-severe). The NSI total score is the sum of severity ratings of the symptoms. The scores are summed to yield a total score ranging from 0 to 88, where the higher the point value, the greater (more severe) the symptoms

    Other Outcome Measures

    1. Change in Number of Standard Drinks Per Week as Assessed by the Timeline Followback (TLFB) [Baseline to Week 8]

      The TLFB interview, using a calendar, asks participants to report the prior week's frequency of alcohol use on each day of the week.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Male and female veterans

    2. Ages 18-65 (inclusive)

    3. A history of mTBI as defined by American Congress of Rehabilitation Medicine (ACRM), in the chronic, stable phase of recovery (>6 months from injury).

    4. Current (past month [30 days]) Hazardous or Harmful Alcohol Use: Hazardous use is drinking that meets NIAAA criteria: Current (past 30 day) weekly drinking, consisting of an average of 15 standard drinks/week for men or 8 standard drinks/week for women. Harmful use is drinking behavior that meets DSM-5 criteria mild AUD.

    5. Participants must express a desire to reduce or stop alcohol use.

    6. Female subjects that must have a negative urine pregnancy test and must be either postmenopausal one year or practicing an effective birth control method.

    Exclusion Criteria:
    1. Unstable psychotic or bipolar disorders, dementia, or other psychiatric disorders judged to be unstable in the clinical judgment of the PI or study physician.

    2. Clinically significant unstable medical conditions, in the clinical judgment of the PI or study physician.

    3. Female patients who are pregnant or nursing.

    4. Concurrent participation in another alcohol treatment study, or in any research study involving medications.

    5. Requiring acute medical detoxification from alcohol based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD).

    6. NAC use in the past week prior to study entry.

    7. Use of AUD treatment medications (disulfiram, naltrexone, or acamprosate) within the past week.

    8. Participants who are legally mandated to participate in an alcohol treatment program.

    9. Participants who have had a suicide attempt in the past 3 months or suicidal ideation, with intent, in the 30 days prior to enrollment.

    10. Participants who in the opinion of the investigator should not be enrolled in the study because of the precautions, warnings or contraindications outlined in the NAC package insert.

    11. Participants with known hypersensitivity to acetylcysteine

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 San Francisco VA Medical Center San Francisco California United States 94121

    Sponsors and Collaborators

    • University of California, San Francisco
    • United States Department of Defense
    • Northern California Institute of Research and Education
    • San Francisco Veterans Affairs Medical Center
    • Institute for Translational Neuroscience

    Investigators

    • Principal Investigator: Steven L. Batki, MD, Unviersity of California, San Francisco

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT02791945
    Other Study ID Numbers:
    • 9236sc
    First Posted:
    Jun 7, 2016
    Last Update Posted:
    May 11, 2021
    Last Verified:
    Apr 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title N-acetylcysteine Placebo
    Arm/Group Description N-acetylcysteine capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling N-acetylcysteine: Experimental supplement Placebo capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling Placebo: Placebo comparator
    Period Title: Overall Study
    STARTED 14 16
    COMPLETED 12 14
    NOT COMPLETED 2 2

    Baseline Characteristics

    Arm/Group Title N-acetylcysteine Placebo Total
    Arm/Group Description N-acetylcysteine capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling N-acetylcysteine: Experimental supplement Placebo capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling Placebo: Placebo comparator Total of all reporting groups
    Overall Participants 14 16 30
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    14
    100%
    16
    100%
    30
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    49
    (8)
    54
    (10)
    52
    (9)
    Sex: Female, Male (Count of Participants)
    Female
    2
    14.3%
    0
    0%
    2
    6.7%
    Male
    12
    85.7%
    16
    100%
    28
    93.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    3
    21.4%
    4
    25%
    7
    23.3%
    Not Hispanic or Latino
    11
    78.6%
    12
    75%
    23
    76.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    3
    21.4%
    4
    25%
    7
    23.3%
    White
    6
    42.9%
    8
    50%
    14
    46.7%
    More than one race
    3
    21.4%
    1
    6.3%
    4
    13.3%
    Unknown or Not Reported
    2
    14.3%
    3
    18.8%
    5
    16.7%
    Region of Enrollment (participants) [Number]
    United States
    14
    100%
    16
    100%
    30
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Percent of Heavy Drinking Days Per Week as Assessed by the Timeline Followback (TFLB)
    Description The TLFB interview, using a calendar, asks participants to report the prior week's frequency of alcohol use on each day of the week.
    Time Frame Baseline to Week 8

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title N-acetylcysteine Placebo
    Arm/Group Description N-acetylcysteine capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling N-acetylcysteine: Experimental supplement Placebo capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling Placebo: Placebo comparator
    Measure Participants 12 14
    Mean (Standard Deviation) [change in percent heavy drinking days/wk]
    26.2
    (0.31)
    26.5
    (0.39)
    2. Primary Outcome
    Title Change in TBI Symptoms as Assessed by the Neurobehavioral Symptom Inventory (NSI)
    Description Participants indicate the extent to which each of the 22 symptoms has disturbed them in the previous 2 weeks on a 5-item scale (0-none to 4-severe). The NSI total score is the sum of severity ratings of the symptoms. The scores are summed to yield a total score ranging from 0 to 88, where the higher the point value, the greater (more severe) the symptoms
    Time Frame Baseline to Week 8

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title N-acetylcysteine Placebo
    Arm/Group Description N-acetylcysteine capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling N-acetylcysteine: Experimental supplement Placebo capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling Placebo: Placebo comparator
    Measure Participants 9 14
    Mean (Standard Deviation) [scores on a scale]
    11.44
    (10.09)
    10
    (10.72)
    3. Other Pre-specified Outcome
    Title Change in Number of Standard Drinks Per Week as Assessed by the Timeline Followback (TLFB)
    Description The TLFB interview, using a calendar, asks participants to report the prior week's frequency of alcohol use on each day of the week.
    Time Frame Baseline to Week 8

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title N-acetylcysteine Placebo
    Arm/Group Description N-acetylcysteine capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling N-acetylcysteine: Experimental supplement Placebo capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling Placebo: Placebo comparator
    Measure Participants 12 14
    Mean (Standard Deviation) [Standard drinks per week]
    24.75
    (25.6)
    18.45
    (30.1)

    Adverse Events

    Time Frame Over 12 weeks.
    Adverse Event Reporting Description We used the Adverse Event Symptom Checklist at every study visit (Visits 0 - 8 and 12), which assessed the most reported adverse events listed in the FDA Prescribing Information.
    Arm/Group Title N-acetylcysteine Placebo
    Arm/Group Description N-acetylcysteine capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling N-acetylcysteine: Experimental supplement Placebo capsules daily - up to 3200 mg Medical Management Counseling: Brief alcohol counseling Placebo: Placebo comparator
    All Cause Mortality
    N-acetylcysteine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/14 (0%) 0/16 (0%)
    Serious Adverse Events
    N-acetylcysteine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/14 (14.3%) 0/16 (0%)
    Musculoskeletal and connective tissue disorders
    Inpatient hospitalization for self-reported "broken back in 3 places". 1/14 (7.1%) 1 0/16 (0%) 0
    Psychiatric disorders
    Inpatient hospitalization/5150 (<72 hours) for suicidal threats while intoxicated 1/14 (7.1%) 1 0/16 (0%) 0
    Other (Not Including Serious) Adverse Events
    N-acetylcysteine Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 14/14 (100%) 16/16 (100%)
    Gastrointestinal disorders
    Nausea 0/14 (0%) 0 5/16 (31.3%) 0
    Vomiting 4/14 (28.6%) 0/16 (0%)
    Upset stomach 3/14 (21.4%) 5/16 (31.3%)
    Skin and subcutaneous tissue disorders
    Flushing 1/14 (7.1%) 4/16 (25%)
    Itching 6/14 (42.9%) 2/16 (12.5%)
    Rash 4/14 (28.6%) 3/16 (18.8%)
    Hives 0/14 (0%) 0 3/16 (18.8%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title Dr. Steven L. Batki, MD
    Organization University of California, San Francisco/San Francisco VA Healthcare System
    Phone 415-221-4810 ext 23671
    Email steven.batki@ucsf.edu
    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT02791945
    Other Study ID Numbers:
    • 9236sc
    First Posted:
    Jun 7, 2016
    Last Update Posted:
    May 11, 2021
    Last Verified:
    Apr 1, 2021