VAT: Topiramate Treatment of Hazardous and Harmful Alcohol Use in Veterans With TBI

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT01750268
• 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)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Traumatic Brain Injury (TBI); Hazardous and Harmful Alcohol Use	Behavioral: Medical Management Counseling; Drug: Topiramate; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Topiramate Treatment of Hazardous and Harmful Alcohol Use in Veterans With TBI
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Oct 1, 2015
• Actual Study Completion Date: Oct 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Topiramate Topiramate capsules daily - up to 300 mg	Behavioral: Medical Management Counseling; Brief alcohol and medication counseling; Drug: Topiramate; Experimental medication; Other Names: Topamax
Placebo Comparator: Placebo Placebo capsules daily - up 300 mg	Behavioral: Medical Management Counseling; Brief alcohol and medication counseling; Drug: Placebo; Placebo comparator

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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 Outcome Measures

1. 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.

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 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.

3. 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).

1. Subjects must express a desire to reduce or stop alcohol use.

2. 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).

3. 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.

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

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT01750268
• Other Study ID Numbers: W81XWH-11-2-0145
• First Posted: Dec 17, 2012
• Last Update Posted: Oct 14, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by University of California, San Francisco: TBI; hazardous and harmful alcohol use; veterans; co-occurring disorders; pharmacotherapy
• Additional relevant MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Alcohol Drinking; Topiramate

Study Results

Participant Flow

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	Topiramate capsules daily - up to 300 mg Medical Management Counseling: Brief alcohol and medication counseling Topiramate: Experimental medication	Placebo capsules daily - up 300 mg Medical Management Counseling: Brief alcohol and medication counseling Placebo: Placebo comparator
Period Title: Overall Study
STARTED	15	17
COMPLETED	13	12
NOT COMPLETED	2	5

Baseline Characteristics

Arm/Group Title	Topiramate	Placebo	Total
Arm/Group Description	Topiramate capsules daily - up to 300 mg Medical Management Counseling: Brief alcohol and medication counseling Topiramate: Experimental medication	Placebo capsules daily - up 300 mg Medical Management Counseling: Brief alcohol and medication counseling Placebo: Placebo comparator	Total of all reporting groups
Overall Participants	15	17	32
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	17 100%	32 100%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.6 (13.5)	48.5 (14.0)	46.6 (13.8)
Sex: Female, Male (Count of Participants)
Female	1 6.7%	1 5.9%	2 6.3%
Male	14 93.3%	16 94.1%	30 93.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 33.3%	2 11.8%	7 21.9%
Not Hispanic or Latino	10 66.7%	15 88.2%	25 78.1%
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%	1 5.9%	1 3.1%
Black or African American	5 33.3%	4 23.5%	9 28.1%
White	7 46.7%	9 52.9%	16 50%
More than one race	2 13.3%	3 17.6%	5 15.6%
Unknown or Not Reported	1 6.7%	0 0%	1 3.1%
Region of Enrollment (participants) [Number]
United States	15 100%	17 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Change in the Number of Drinking Days Per Week as Assessed by the Timeline Followback (TLFB)
Description	Using a calendar, participants provide retrospective estimates of daily drinking over a specified period.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	Topiramate capsules daily - up to 300 mg Medical Management Counseling: Brief alcohol and medication counseling Topiramate: Experimental medication	Placebo capsules daily - up 300 mg Medical Management Counseling: Brief alcohol and medication counseling Placebo: Placebo comparator
Measure Participants	15	17
Mean (Standard Deviation) [Drinking Days per week]	2.2 (1.8)	1.6 (2.1)

2. Secondary Outcome

Title	Change in TBI Symptom Severity 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 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Topiramate	Placebo
Arm/Group Description	Topiramate capsules daily - up to 300 mg Medical Management Counseling: Brief alcohol and medication counseling Topiramate: Experimental medication	Placebo capsules daily - up 300 mg Medical Management Counseling: Brief alcohol and medication counseling Placebo: Placebo comparator
Measure Participants	15	17
Mean (Standard Deviation) [scores on a scale]	16.3 (13.1)	19.3 (15.1)

3. Other Pre-specified Outcome

Title	Change in Alcohol Use as Assessed by the Timeline Followback (TLFB)
Description	Using a calendar, participants provide retrospective estimates of daily drinking over a specified period.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	From enrollment through study completion, an average of 12 weeks
Arm/Group Title	Topiramate		Placebo
Arm/Group Description	Topiramate capsules daily - up to 300 mg Medical Management Counseling: Brief alcohol and medication counseling Topiramate: Experimental medication		Placebo capsules daily - up 300 mg Medical Management Counseling: Brief alcohol and medication counseling Placebo: Placebo comparator
All Cause Mortality
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/17 (0%)
Serious Adverse Events
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/15 (20%)		1/17 (5.9%)
Cardiac disorders
Inpatient medical hospitalization for an episode of chest pain in the context of cocaine use	1/15 (6.7%)	2	0/17 (0%)	0
Gastrointestinal disorders
Inpatient medical hospitalization for planned distal pancreatectomy and splenectomy	0/15 (0%)	0	1/17 (5.9%)	1
Psychiatric disorders
Voluntary psych inpatient admission due to homicidal ideation in the context of heavy cocaine use	1/15 (6.7%)	1	0/17 (0%)	0
Inpatient medical hospitalization due to alcohol withdrawal	1/15 (6.7%)	1	0/17 (0%)	0
Other (Not Including Serious) Adverse Events
	Topiramate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/15 (100%)		17/17 (100%)
Ear and labyrinth disorders
Dizziness	4/15 (26.7%)		4/17 (23.5%)
Eye disorders
Abnormal vision	5/15 (33.3%)		1/17 (5.9%)
Eye pain	3/15 (20%)		4/17 (23.5%)
Gastrointestinal disorders
Loss of appetite	4/15 (26.7%)		6/17 (35.3%)
Diarrhea	6/15 (40%)		3/17 (17.6%)
General disorders
Fatigue	2/15 (13.3%)		4/17 (23.5%)
Sleepiness	7/15 (46.7%)		3/17 (17.6%)
Nervous system disorders
Numbness and tingling	5/15 (33.3%)		5/17 (29.4%)
Change in sense of taste	8/15 (53.3%)		5/17 (29.4%)
Difficulty with concentration and attention	1/15 (6.7%)		2/17 (11.8%)
Difficulty with memory	1/15 (6.7%)		3/17 (17.6%)
Slow thinking	3/15 (20%)		3/17 (17.6%)
Confusion	4/15 (26.7%)		6/17 (35.3%)
Language problems	4/15 (26.7%)		3/17 (17.6%)
Psychiatric disorders
Nervousness	2/15 (13.3%)		2/17 (11.8%)
Depression	3/15 (20%)		3/17 (17.6%)
Suicidal thoughts and actions	4/15 (26.7%)		4/17 (23.5%)
Skin and subcutaneous tissue disorders
Itching	6/15 (40%)		5/17 (29.4%)

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.