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

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury (TBI); Hazardous and Harmful Alcohol Use
• Intervention / Treatment: Drug: Placebo; Behavioral: Medical Management Counseling; Drug: Topiramate

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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	Drug: Placebo; Placebo comparator; Behavioral: Medical Management Counseling; Brief alcohol and medication counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: United States Department of Defense; Northern California Institute of Research and Education; San Francisco Veterans Affairs Medical Center

Publications and helpful links

General Publications

• Pennington DL, Bielenberg J, Lasher B, Herbst E, Abrams G, Novakovic-Agopian T, Batki SL. A randomized pilot trial of topiramate for alcohol use disorder in veterans with traumatic brain injury: Effects on alcohol use, cognition, and post-concussive symptoms. Drug Alcohol Depend. 2020 Sep 1;214:108149. doi: 10.1016/j.drugalcdep.2020.108149. Epub 2020 Jul 2.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: November 28, 2012
• First Submitted That Met QC Criteria: December 12, 2012
• First Posted (Estimate): December 17, 2012

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: September 18, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: pharmacotherapy; TBI; veterans; co-occurring disorders; hazardous and harmful alcohol use
• Additional Relevant MeSH Terms: Drinking Behavior; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Alcohol Drinking; Brain Injuries; Brain Injuries, Traumatic; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: W81XWH-11-2-0145