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

NCT01750268 | Completed Phase 4 Results DMC

• 1 other identifier: W81XWH-11-2-0145
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Traumatic Brain Injury (TBI); Hazardous and Harmful Alcohol Use

Keywords

TBI; hazardous and harmful alcohol use; veterans; co-occurring disorders; pharmacotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in TBI Symptom Severity as Assessed by the Neurobehavioral Symptom Inventory (NSI)

  Baseline to Week 12

Other Outcomes (1)

• Change in Alcohol Use as Assessed by the Timeline Followback (TLFB)

  Baseline to Week 12

Study Arms (2)

Topiramate

EXPERIMENTAL

Topiramate capsules daily - up to 300 mg

Behavioral: Medical Management Counseling; Drug: Topiramate

Placebo

PLACEBO COMPARATOR

Placebo capsules daily - up 300 mg

Behavioral: Medical Management Counseling; Drug: Placebo

Interventions

Medical Management Counseling BEHAVIORAL

Brief alcohol and medication counseling

Placebo; Topiramate

Topiramate DRUG

Experimental medication

Also known as: Topamax

Topiramate

Placebo DRUG

Placebo comparator

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female veterans.
• Ages 18 to 65 (inclusive).
• 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:
• a. loss of consciousness of up to 30 minutes;
• b. any loss of memory for events immediately before or after the event;
• c. any alteration in mental state at the time of the event, for example feeling dazed, disoriented, or confused; and
• 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:
• This is the most common description of patients currently served by our VA facilities.
• Studies at this stable phase will facilitate detection of otherwise subtle changes as findings are less likely to be confounded by 'spontaneous' recovery.
• \. Current (past month) hazardous alcohol use or harmful alcohol use.
• 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.
• 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).
• \. Subjects must express a desire to reduce or stop alcohol use.
• \. 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).

You may not qualify if:

• Psychotic disorders, bipolar disorders, dementia, or other psychiatric disorders judged to be unstable.
• 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.
• History of glaucoma.
• History of kidney stones.
• Concurrent participation in another alcohol treatment study or any study involving medications.
• Female patients who are pregnant or lactating.
• Topiramate use in the past week prior to study entry.
• Use of medications for alcohol dependence (disulfiram, naltrexone, or acamprosate) within the past week.
• 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).
• Subjects who are legally mandated to participate in an alcohol treatment program.
• Subjects who have had a suicide attempt in the past 6 months or suicidal ideation, with intent, in the 30 days prior to enrollment.
• 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.
• Subjects with seizure disorders.
• Subjects currently being treated with another anticonvulsant.
• 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.

Sponsors & Collaborators

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

Study Sites (1)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

Related Publications (1)

• 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.

  PMID: 32712569 RESULT

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Topiramate

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Steven L. Batki, MD
• Organization: San Francisco VA Health Care System/University of California, San Francisco

steven.batki@ucsf.edu

415-221-4810

Study Officials

• Steven L. Batki, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 17, 2012
• Study Start: November 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 14, 2020
• Results First Posted: October 14, 2020

Record last verified: 2020-09

Locations

US (1)