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 proposed project is to improve the treatment of veterans with co-occurring traumatic brain injury (TBI) and hazardous or harmful alcohol use. The PI and coinvestigators will conduct a pilot controlled clinical trial of topiramate for the treatment of these co-occurring disorders.
Interventions
BEHAVIORALMedical Management Counseling
Brief alcohol and medication counseling
DRUGTopiramate
Experimental medication
DRUGPlacebo
Placebo comparator
Sponsors
United States Department of Defense
Northern California Institute of Research and Education
San Francisco Veterans Affairs Medical Center
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 to 65 (inclusive). 3. TBI: a history of mild traumatic brain injury, as defined by American Congress of Rehabilitation Medicine (ACRM) and VA, in the chronic, stable phase of recovery (\>6 months from injury). The ACRM defines mild TBI as a traumatically-induced physiological disruption of brain function as demonstrated by at least one of the following: 3.a. loss of consciousness of up to 30 minutes; 3.b. any loss of memory for events immediately before or after the event; 3.c. any alteration in mental state at the time of the event, for example feeling dazed, disoriented, or confused; and 3.d. a focal neurological deficit or deficits that may or may not have been transient, for example loss of coordination, speech difficulties, or double vision. ACRM's definition further specifies that a person may be designated as having a mild TBI only if the severity of the injury does not include a loss of consciousness that lasted longer than 30 minutes, and post-traumatic amnesia lasting longer than 24 hours. Rationale: 1. This is the most common description of patients currently served by our VA facilities. 2. Studies at this stable phase will facilitate detection of otherwise subtle changes as findings are less likely to be confounded by 'spontaneous' recovery. 4\. Current (past month) hazardous alcohol use or harmful alcohol use. 4.a. Hazardous use is drinking that must meet criteria for at-risk or heavy drinking by National Institute on Alcohol Abuse and Alcoholism (NIAAA) criteria: Subjects must report current (past 30 day) at-risk or heavy drinking on an average weekly basis, consisting of an average of 15 or more standard drinks per week for men and 8 or more standard drinks per week for women during the 30 days prior to Screening Visit 1 as measured by the Alcohol Timeline Followback (TLFB) method. 4.b. Harmful use is drinking behavior that meets Diagnostic and Statistical Manual (DSM)-IV diagnostic criteria for an Alcohol Use Disorder (Alcohol Dependence or Alcohol Abuse). 5\. Subjects must express a desire to reduce or stop alcohol use. 6\. Female subjects must have a negative urine pregnancy test and must be either postmenopausal for at least 1 year or practicing an effective method of birth control (e.g., surgically sterile, spermicide with barrier, male partner sterilization; or absent and agrees to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence). 7\. Subjects must have a Breath Alcohol Concentration (BAC) of less than 0.02% when signing the informed consent form.
Exclusion criteria
1. Psychotic disorders, bipolar disorders, dementia, or other psychiatric disorders judged to be unstable. 2. Subjects known to have clinically significant unstable medical conditions, including but not limited to: Clinically significant renal disease and/or impaired renal function as defined by clinically significant elevation of blood urea nitrogen (BUN) or creatinine or an estimated creatinine clearance of \< 60 mL/min; AST and/or ALT \> 5 times the upper limit of the normal range and/or a serum bilirubin \> 2 times the upper limit of normal. 3. History of glaucoma. 4. History of kidney stones. 5. Concurrent participation in another alcohol treatment study or any study involving medications. 6. Female patients who are pregnant or lactating. 7. Topiramate use in the past week prior to study entry. 8. Use of medications for alcohol dependence (disulfiram, naltrexone, or acamprosate) within the past week. 9. Needing acute medical detoxification from alcohol based on a score of 12 or more on the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD). 10. Subjects who are legally mandated to participate in an alcohol treatment program. 11. Subjects who have had a suicide attempt in the past 6 months or suicidal ideation, with intent, in the 30 days prior to enrollment. 12. Subjects who have previously been treated with topiramate for any reason and discontinued treatment due to an adverse event or due to a hypersensitivity reaction to topiramate. 13. Subjects with seizure disorders. 14. Subjects currently being treated with another anticonvulsant. 15. Subjects who in the opinion of the investigator should not be enrolled in the study because of the precautions, warnings or contraindications outlined in the topiramate package insert.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Drinking Days Per Week as Assessed by the Timeline Followback (TLFB) | Baseline to Week 12 | Using a calendar, participants provide retrospective estimates of daily drinking over a specified period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in TBI Symptom Severity as Assessed by the Neurobehavioral Symptom Inventory (NSI) | Baseline to Week 12 | 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 Alcohol Use as Assessed by the Timeline Followback (TLFB) | Baseline to Week 12 | Using a calendar, participants provide retrospective estimates of daily drinking over a specified period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Topiramate Topiramate capsules daily - up to 300 mg
Medical Management Counseling: Brief alcohol and medication counseling
Topiramate: Experimental medication | 15 |
| Placebo Placebo capsules daily - up 300 mg
Medical Management Counseling: Brief alcohol and medication counseling
Placebo: Placebo comparator | 17 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Physician Decision | 0 | 3 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Topiramate | 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 | 15 Participants | 17 Participants | 32 Participants |
| Age, Continuous | 44.6 Years STANDARD_DEVIATION 13.5 | 48.5 Years STANDARD_DEVIATION 14 | 46.6 Years STANDARD_DEVIATION 13.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 15 Participants | 25 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 | 5 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 7 Participants | 9 Participants | 16 Participants |
| Region of Enrollment United States | 15 participants | 17 participants | 32 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 17 |
| other Total, other adverse events | 15 / 15 | 17 / 17 |
| serious Total, serious adverse events | 3 / 15 | 1 / 17 |
Outcome results
Primary
Change in the Number of Drinking Days Per Week as Assessed by the Timeline Followback (TLFB)
Using a calendar, participants provide retrospective estimates of daily drinking over a specified period.
Time frame: Baseline to Week 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change in the Number of Drinking Days Per Week as Assessed by the Timeline Followback (TLFB) | 2.2 Drinking Days per week | Standard Deviation 1.8 |
| Placebo | Change in the Number of Drinking Days Per Week as Assessed by the Timeline Followback (TLFB) | 1.6 Drinking Days per week | Standard Deviation 2.1 |
Secondary
Change in TBI Symptom Severity 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 12
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Topiramate | Change in TBI Symptom Severity as Assessed by the Neurobehavioral Symptom Inventory (NSI) | 16.3 scores on a scale | Standard Deviation 13.1 |
| Placebo | Change in TBI Symptom Severity as Assessed by the Neurobehavioral Symptom Inventory (NSI) | 19.3 scores on a scale | Standard Deviation 15.1 |
Other Pre-specified
Change in Alcohol Use as Assessed by the Timeline Followback (TLFB)
Using a calendar, participants provide retrospective estimates of daily drinking over a specified period.
Time frame: Baseline to Week 12