Official Title: “Adjunctive Topiramate for Treatment of Alcohol Dependence in Patients With Bipolar Disorder”

The purpose of this study is determine whether the use of topiramate is effective in the treatment of alcohol dependence (i.e. decreases drinking) in patients with bipolar disorder.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: July 2012

Alcohol and substance use disorders are more common in bipolar disorder bipolar disorder than in any other DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) Axis I disorder, estimated to occur in up to 60% of patients with bipolar disorder. Alcohol use is associated with poor outcome in bipolar disorder, and yet these co-occurring conditions are understudied. To date, there is only one published placebo-controlled trial of an agent for the treatment of alcohol dependence alcohol dependence in bipolar disorder. The purpose of the proposed study is to evaluate the efficacy of a topiramate as a treatment for alcohol dependence in patients with bipolar disorder. This is a 12-week, randomized, placebo-controlled study of the efficacy of topiramate adjunctive to standard treatment for bipolar disorder in patients with alcohol dependence and bipolar disorder. Additional aims of the study are to document the safety and tolerability of topiramate in this population, and to evaluate to effect of decreased drinking on mood symptoms. The study involves the enrollment of a total of 80 patients with co-occurring alcohol dependence and bipolar disorder over the course of 40 months at the Massachusetts General Hospital (MGH) Bipolar Clinic and Research Program (BCRP) (www.manicdepressive.org). With a conservative estimate of a 30% dropout rate, approximately 56 of the 80 patients with these two comorbid conditions will complete 12 weeks treatment with either topiramate or placebo.

Intervention(s) in this Clinical Trial

• Drug: Topiramate
  • Medication will be titrated slowly over 5 weeks from 25 mg qD to 150 mg BID in an effort to minimize side effects and the possible unblinding of participants and raters to treatment. Subjects will continue on 150 mg BID for Weeks 5-12 of the study.
• Other: Placebo
  • placebo

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Topiramate -- Subjects will continue Weeks 5-12 of the study.
• Placebo Comparator: 2
  • placebo

Primary Measures

• Amount of alcohol consumed
  • Time Frame: 12 Weeks
    Safety Issue?: Yes

Secondary Measures

• Safety and tolerability of topiramate.
  • Time Frame: 12 Weeks
    Safety Issue?: Yes
• Effect of decreased drinking on mood symptoms
  • Time Frame: 12 Weeks
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Age 18+
• 2. Written informed consent.
• 3. Meet DSM-IV criteria (by SCID) for alcohol dependence.
• 4. Meet DSM-IV criteria (by SCID) for bipolar disorder I or II disorder.
• 5. ≥ 8 heavy drinking days (defined as ≥ 5 standard drinks per day for men, ≥ 4 standard drinks per day for women) in the prior 4 weeks.
• 6. During the baseline visit, patients must be on a stable dose of accepted maintenance treatment for bipolar disorder for the past 4 weeks. If the subject is on more than one agent, at least one agent must be adequately dosed.
• 7. Antidepressant treatment is permitted if the dose has been stable for the past 4 weeks.

Exclusion Criteria:

• 1. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy). Because of the risk of the lowering of oral contraceptive blood levels with topiramate, women whose sole means of contraception is oral contraceptives or hormonal implants will be asked to use an additional barrier method of birth control during treatment with the study drug.
• 2. Women who are lactating.
• 3. Age under 18.
• 4. Patients who do not have ≥ 8 heavy drinking days in the 4 weeks prior to the baseline visit.
• 5. Important alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for
• Alcohol-Revised, CIWA-Ar, score > 15)
• 6. Urine toxicological screen positive for amphetamines or cocaine.
• 7. Meets DSM-IV criteria for current substance dependence for drugs other than cannabis or nicotine.
• 8. Currently meets full DSM-IV criteria for major depressive, manic, hypomanic, or mixed episode.
• 9. Serious suicide or homicide risk, as assessed by evaluating clinician.
• 10. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.
• 11. History of nephrolithiasis, or treatment with any drug associated with nephrolithiasis.
• 12. Current treatment with zonisamide.
• 13. Current treatment with any carbonic anhydrase inhibitors, including acetazolamide, dorzolamide, and methozolamide.
• 14. Current treatment with any drug known to decrease drinking.
• 15. Current psychosocial treatment (other than self-help groups) more than 1X/month.
• Psychosocial treatment is defined as individual or group psychotherapy (not including 12-step treatments such as AA or NA).
• 16. Any psychotic disorder, including schizoaffective disorder (current or past).
• 17. Clinical or laboratory evidence of untreated hypothyroidism.
• 18. Patients with a diagnosis or history of glaucoma
• 19. Patients requiring excluded medications (see table below for details).
• 20. Psychotic features in the current episode or a history of a psychotic disorder, as assessed by SCID.
• 21. Past intolerance to topiramate.
• 22. Any use of topiramate in the past 12 months.
• 23. Any investigational psychotropic drug within the last 3 months.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Overall Clinical Trial Officials and Contacts

Michael J. Ostacher, MD, MPH Principal Investigator Massachusetts General Hospital  

Overall Contact: Michael J. Ostacher, MD, MPH 617-726-5258 mostacher@partners.org

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00572117

Study ID Number: TIL-NIAAA-016340-01

ClinicalTrials.gov Identifier: NCT00572117

Health Authority: United States: Federal Government

Massachusetts General Hospital Bipolar Clinic and Research Program