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

This study has been completed.
Sponsor:
Collaborators:
United States Department of Defense
Northern California Institute of Research and Education
San Francisco Veterans Affairs Medical Center
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01750268
First received: November 28, 2012
Last updated: December 4, 2015
Last verified: December 2015
  Purpose
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 Intervention Phase
Traumatic Brain Injury (TBI)
Hazardous and Harmful Alcohol Use
Behavioral: Medical Management Counseling
Drug: Topiramate
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Change in the number of drinking days as assessed by the Timeline Followback (TLFB) [ Time Frame: Basline to Week 12 ] [ Designated as safety issue: Yes ]
    Using a calendar, participants provide retrospective estimates of daily drinking over a specified period.


Secondary Outcome Measures:
  • Change in TBI symptoms as assessed by the Neurobehavioral Symptom Inventory (NSI) [ Time Frame: Basline to Week 12 ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Change in alcohol use as assessed by the Timeline Followback (TLFB) [ Time Frame: Baseline to Week 12 ] [ Designated as safety issue: Yes ]
    Using a calendar, participants provide retrospective estimates of daily drinking over a specified period.


Enrollment: 32
Study Start Date: November 2012
Study Completion Date: October 2015
Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Topiramate
Topiramate capsules daily - up to 300 mg
Behavioral: Medical Management Counseling
Brief alcohol and medication counseling
Drug: Topiramate
Experimental medication
Other Name: Topamax
Placebo Comparator: Placebo
Placebo capsules daily - up 300 mg
Behavioral: Medical Management Counseling
Brief alcohol and medication counseling
Drug: Placebo
Placebo comparator

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01750268

Locations
United States, California
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
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01750268     History of Changes
Other Study ID Numbers: W81XWH-11-2-0145 
Study First Received: November 28, 2012
Last Updated: December 4, 2015
Health Authority: United States: Department of Defense
United States: UCSF Gallo Clinic and Research Center
United States: Food and Drug Administration
United States: Veterans Administration

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
Alcohol Drinking
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries
Drinking Behavior
Topiramate
Anticonvulsants
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs
Anti-Obesity Agents

ClinicalTrials.gov processed this record on September 23, 2016