Hazardous and Harmful Alcohol Use, Traumatic Brain Injury (TBI)
Conditions
Keywords
TBI, hazardous and harmful alcohol use, Veterans, co-occurring disorders, pharmacotherapy
Brief summary
The goal of the project is to improve the care of Veterans with mild traumatic brain injury (mTBI) and unhealthy alcohol use.
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.
Interventions
BEHAVIORALMedical Management Counseling
Brief alcohol counseling
DRUGN-acetylcysteine
Experimental supplement
DRUGPlacebo
Placebo comparator
Sponsors
United States Department of Defense
Northern California Institute of Research and Education
San Francisco Veterans Affairs Medical Center
Institute for Translational Neuroscience
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| N-acetylcysteine N-acetylcysteine capsules daily - up to 3200 mg
Medical Management Counseling: Brief alcohol counseling
N-acetylcysteine: Experimental supplement | 14 |
| Placebo Placebo capsules daily - up to 3200 mg
Medical Management Counseling: Brief alcohol counseling
Placebo: Placebo comparator | 16 |
| Total | 30 |
Baseline characteristics
| Characteristic | N-acetylcysteine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 16 Participants | 30 Participants |
| Age, Continuous | 49 Years STANDARD_DEVIATION 8 | 54 Years STANDARD_DEVIATION 10 | 52 Years STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 12 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 14 Participants |
| Region of Enrollment United States | 14 participants | 16 participants | 30 participants |
| Sex: Female, Male Female | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 16 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 16 |
| other Total, other adverse events | 14 / 14 | 16 / 16 |
| serious Total, serious adverse events | 2 / 14 | 0 / 16 |
Outcome results
Primary
Change in Percent of Heavy Drinking Days Per Week as Assessed by the Timeline Followback (TFLB)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Percent of Heavy Drinking Days Per Week as Assessed by the Timeline Followback (TFLB) | 26.2 change in percent heavy drinking days/wk | Standard Deviation 0.31 |
| Placebo | Change in Percent of Heavy Drinking Days Per Week as Assessed by the Timeline Followback (TFLB) | 26.5 change in percent heavy drinking days/wk | Standard Deviation 0.39 |
Primary
Change in TBI Symptoms as Assessed by the Neurobehavioral Symptom Inventory (NSI)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in TBI Symptoms as Assessed by the Neurobehavioral Symptom Inventory (NSI) | 11.44 scores on a scale | Standard Deviation 10.09 |
| Placebo | Change in TBI Symptoms as Assessed by the Neurobehavioral Symptom Inventory (NSI) | 10 scores on a scale | Standard Deviation 10.72 |
Other Pre-specified
Change in Number of Standard Drinks Per Week as Assessed by the Timeline Followback (TLFB)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| N-acetylcysteine | Change in Number of Standard Drinks Per Week as Assessed by the Timeline Followback (TLFB) | 24.75 Standard drinks per week | Standard Deviation 25.6 |
| Placebo | Change in Number of Standard Drinks Per Week as Assessed by the Timeline Followback (TLFB) | 18.45 Standard drinks per week | Standard Deviation 30.1 |