Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy

NCT01087736 | Completed Phase 4 Results DMC

• 2 other identifiers: H5220-34690-01DAMD17-03-1-0532
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed project aims to:

1. 1.Obtain a preliminary assessment of the efficacy of topiramate treatment in reducing alcohol use in veterans with Post Traumatic Stress Disorder (PTSD) and alcohol dependence;
2. 2.Obtain preliminary assessments of safety/tolerability of topiramate in these patients;
3. 3.Assess the feasibility of recruitment and retention for topiramate treatment in this comorbid population; and 4) to inform the design of a planned subsequent larger controlled trial of topiramate.

Conditions

PTSD; Alcohol Abuse; Alcoholism

Keywords

PTSD; Alcohol abuse; Alcoholism; Topiramate; Stress Disorder, Post Traumatic; Chronic Post-Traumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Percent Drinking Days (%DD)

  Alcohol consumption was assessed at baseline and weekly during the treatment phase (12 weeks) using the Time Line Follow Back (TLFB) interview which yields number of days of alcohol use (DD). DD: day on which alcohol was consumed Standard alcoholic drink defined as containing 13.6 g of pure alcohol.

  Weekly, weeks 1-12, average

Other Outcomes (1)

• PTSD Symptom Severity

  Weeks 4, 8, 12

Study Arms (2)

Topiramate

EXPERIMENTAL

Participants will be randomly assigned to either the topiramate arm or placebo arm. Neither the participant nor the researchers will know which arm the participant is in. Participants in the topiramate arm will be ingesting daily doses of topiramate that will gradually increase to a maximum, and then taper off.

Drug: Topiramate

Placebo

PLACEBO COMPARATOR

The Drug Product Services Laboratory at UCSF will purchase and supply our lab with USP or NF grade topiramate study capsules and matching placebo capsules. Randomization will be done by a consulting biostatistician, who will be the only one to know which participants are assigned to placebo. Dosing will follow the same procedures as with topiramate in that arm of the study. If adverse events occur, there will be a procedure in place for unblinding only that participant.

Other: Placebo administration

Interventions

Topiramate DRUG

After random assignment, topiramate will be titrated up over 5 weeks. Dosing begins at 25 mg per day, and increase in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Patients will receive the highest dose tolerated, not to exceed 300 mg per day. Adjustments are permitted throughout titration. Once maximum tolerated dosage is reached, subjects will be asked to maintain dosage for remainder of the treatment phase. Upon completing the 6 week maintenance period subjects will taper off over a 7-day period (Week 12). If subjects experience significant side effects, the dosage may be adjusted.

Also known as: Topamax, Qnexa

Topiramate

Placebo administration OTHER

Placebo pills will be prepared by the UCSF pharmacy which will be indistinguishable from the topiramate pills used in that arm. Both topiramate and placebo will then be delivered to the VA pharmacy. A consulting biostatistician will randomly assign participants to either the topiramate or placebo group. The dosing of placebo pills will follow the same regimen as outlined for the topiramate arm. In the event of a safety issue, there will be a procedure for unblinding only that participant.

Also known as: Placebo, Sugar pill

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 outpatient veterans.
• Current DSM-IV diagnosis of PTSD.
• Current (past month) DSM-IV diagnosis of an Alcohol Use Disorder.
• Must meet criteria for "heavy" or "at-risk" drinking by NIAAA thresholds.
• Receiving treatment for PTSD.
• Must express desire to reduce alcohol consumption.
• Female subjects must have negative urine pregnancy test and must be either postmenopausal for at least one year, or practicing an effective method of birth control.
• Must have a BAC of less than 0.02% when signing the informed consent.

You may not qualify if:

• Psychotic disorders, bipolar disorder, 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 BUN or creatinine or an estimated creatinine clearance of \< 60 mL/min; AST (SGOT) and/or ALT (SGPT) \>3 times the upper limit of the normal range and/or an increased serum bilirubin \>2 times the upper limit of normal; seizure disorders.
• Subjects with glaucoma.
• Subjects with a history of kidney stones.
• Subjects with a history of renal disease.
• Concurrent participation in another treatment study.
• Female patients who are pregnant or lactating.
• Current topiramate use or use within the past 4 weeks.
• Current medications for alcohol dependence or use within the past 4 weeks.
• 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 or suicidal ideation in the 6 months 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 that require anticonvulsant medications
• Subjects currently being treated with another anticonvulsant.

Sponsors & Collaborators

• University of California, San Francisco: lead
• United States Department of Defense: collaborator
• US Department of Veterans Affairs: collaborator

Study Sites (1)

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

Related Publications (8)

• Alderman CP, McCarthy LC, Condon JT, Marwood AC, Fuller JR. Topiramate in combat-related posttraumatic stress disorder. Ann Pharmacother. 2009 Apr;43(4):635-41. doi: 10.1345/aph.1L578. Epub 2009 Mar 31.

  PMID: 19336652 BACKGROUND

• Anton RF, O'Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM, Gastfriend DR, Hosking JD, Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL, Swift R, Weiss RD, Williams LD, Zweben A; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006 May 3;295(17):2003-17. doi: 10.1001/jama.295.17.2003.

  PMID: 16670409 BACKGROUND

• Anton RF, Moak DH, Latham P. The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995 Feb;19(1):92-9. doi: 10.1111/j.1530-0277.1995.tb01475.x.

  PMID: 7771669 BACKGROUND

• Baker F, Johnson MW, Bickel WK. Delay discounting in current and never-before cigarette smokers: similarities and differences across commodity, sign, and magnitude. J Abnorm Psychol. 2003 Aug;112(3):382-92. doi: 10.1037/0021-843x.112.3.382.

  PMID: 12943017 BACKGROUND

• Batki SL, Dimmock JA, Wade M, Gately PW, Cornell M, Maisto SA, Carey KB, Ploutz-Snyder R. Monitored naltrexone without counseling for alcohol abuse/dependence in schizophrenia-spectrum disorders. Am J Addict. 2007 Jul-Aug;16(4):253-9. doi: 10.1080/10550490701389732.

  PMID: 17661192 BACKGROUND

• Beckham JC, Crawford AL, Feldman ME. Trail making test performance in Vietnam combat veterans with and without posttraumatic stress disorder. J Trauma Stress. 1998 Oct;11(4):811-9. doi: 10.1023/A:1024409903617.

  PMID: 9870231 BACKGROUND

• Berlant J, van Kammen DP. Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry. 2002 Jan;63(1):15-20. doi: 10.4088/jcp.v63n0104.

  PMID: 11838620 BACKGROUND

• Berlant JL. Prospective open-label study of add-on and monotherapy topiramate in civilians with chronic nonhallucinatory posttraumatic stress disorder. BMC Psychiatry. 2004 Aug 18;4:24. doi: 10.1186/1471-244X-4-24.

  PMID: 15315714 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Alcoholism

Interventions

Topiramate; Qnexa; Sugars

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Fructose; Hexoses; Monosaccharides; Carbohydrates; Ketoses

Results Point of Contact

• Title: David L. Pennington, PhD (Research Psychologist II)
• Organization: University of California, San Francisco

david.pennington2@va.gov

415-221-4810

Study Officials

• Steven L. Batki, MD

  University of California, San Francisco; Department of Veteran's Affairs

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: March 15, 2010
• First Posted: March 16, 2010
• Study Start: April 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: December 1, 2013
• Last Updated: June 3, 2014
• Results First Posted: June 3, 2014

Record last verified: 2014-05

Locations

US (1)