NAC: N-acetylcysteine Treatment of Alcohol Use Disorder In Veterans With TBI
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
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:
|
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
- 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.
- 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
- 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
Inclusion Criteria:
-
Male and female veterans
-
Ages 18-65 (inclusive)
-
A history of mTBI as defined by American Congress of Rehabilitation Medicine (ACRM), in the chronic, stable phase of recovery (>6 months from injury).
-
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.
-
Participants must express a desire to reduce or stop alcohol use.
-
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:
-
Unstable psychotic or bipolar disorders, dementia, or other psychiatric disorders judged to be unstable in the clinical judgment of the PI or study physician.
-
Clinically significant unstable medical conditions, in the clinical judgment of the PI or study physician.
-
Female patients who are pregnant or nursing.
-
Concurrent participation in another alcohol treatment study, or in any research study involving medications.
-
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).
-
NAC use in the past week prior to study entry.
-
Use of AUD treatment medications (disulfiram, naltrexone, or acamprosate) within the past week.
-
Participants who are legally mandated to participate in an alcohol treatment program.
-
Participants who have had a suicide attempt in the past 3 months or suicidal ideation, with intent, in the 30 days prior to enrollment.
-
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.
-
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.- 9236sc
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
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)
|
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)
|
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
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 |
steven.batki@ucsf.edu |
- 9236sc