Topiramate for Alcohol and Cocaine Dependence

Condition(s) targeted: Alcoholism; Cocaine Dependence

Intervention: Topiramate (Drug); placebo (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: University of Pennsylvania

Official(s) and/or principal investigator(s):
Kyle M Kampman, MD, Principal Investigator, Affiliation: University of Pennsylvania

Overall contact:
Kyle M Kampman, MD, Phone: 215-222-3200, Email: kampman_k@mail.trc.upenn.edu

The primary purpose of this study is to test the effectiveness of topiramate for the treatment of combined alcohol and cocaine dependence. Topiramate is approved for the treatment of seizures. It has not been proven to be effective for the treatment of alcohol or cocaine dependence.

Official title: A Phase II, Randomized, Double-blind, Placebo-Controlled, Pilot Trial of Topiramate for Alcohol and Comorbid Cocaine Dependence

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study

Primary outcome:

Days abstinent from drinking and frequency of heavy drinking days as measured by the Time Line Follow-Back during the medication/placebo treatment phase, compared to placebo-treated subjects.

Fewer days of cocaine use as measured by the Time Line Follow Back and confirmed by urine drug screen during the medication/placebo treatment phase, compared to placebo-treated subjects.

Secondary outcome:

Days abstinent from drinking and frequency of heavy drinking days as measured by the Time Line Follow-Back during the the follow-up period after discontinuing medication, compared to placebo-treated subjects.

Fewer days of cocaine use as measured by the Time Line Follow Back in the follow-up period after discontinuing medication, compared to placebo-treated subjects.

Days abstinent from drinking, frequency of heavy drinking days, and cocaine use (confirmed by urine drug screen) as measured by the Time Line Follow-Back during the treatment phase, compared to less topiramate-adherent (<80% pills taken).

The Penn Alcohol Craving Scale and the Minnesota Cocaine Craving Scale during the medication treatment phase, compared to placebo-treated subjects.

Detailed description: The purpose of this study is to evaluate the efficacy of 300 mg/day of topiramate for the treatment of 200 treatment-seeking alcohol dependent outpatients with comorbid cocaine dependence in a double-blind, placebo-controlled 14-week trial, with a 6-month follow-up (3months after completing medications).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male and females, 18 years or older.

- Meets DSM-IV criteria for current diagnoses of cocaine and alcohol dependence,

determined by the SCID-IV.

- In the past 30 days, used no less than $200-worth of cocaine and meets the following

drinking criteria as measured by the Timeline Followback (TLFB) (Sobell and Sobell, 1995) a. drank within 30 days of intake day, b. reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) in a consecutive 30-day period over the 90-day period prior to starting intake (i. e., a minimum of 40% days drinking), and c. has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males and 4 or more drinks per day in females) in this same pre-treatment period.

- Two consecutive days of abstinence from cocaine and alcohol, determined by

self-reports and confirmed by negative urine toxicology screens, a negative breathalyzer tests, and collateral report, a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR) (Sullivan et al., 1989) score below eight,. Subjects will be encouraged to achieve 3 consecutive days of abstinence, however, subjects who have achieved 2 consecutive days of abstinence will be included with the approval of the principal investigator. We anticipate that these subjects will comprise less than 5% of total enrolled subjects. Subjects will be given 2 additional weeks beyond the screening week to attain the appropriate period of cocaine and alcohol abstinence prior to randomization.

- Lives a commutable distance from the TRC and agrees to attend all research visits

including follow-up visits.

- Speaks, understands, and prints in English.

Exclusion Criteria:

- Abstinent from cocaine or alcohol for 30 consecutive days prior to signing consent

form.

- Meets DSM-IV criteria for dependence on any substance other than cocaine and alcohol

(except nicotine and cannabis), determined by the SCID.

- Needs treatment with any psychoactive medications including any anti-seizure

medications (with the exception of Benadryl used sparingly, if necessary, for sleep).

- Current use of phenytoin or any drug of similar class.

- Meets DSM-IV criteria for for schizophrenia or any psychotic disorder, or organic

mental disorder. Subject meets current DSM-IV diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation.

- Has evidence of a history of significant hematological, pulmonary, endocrine,

cardiovascular, renal or gastrointestinal disease.

- Severe physical or medical illnesses such as AIDS, active hepatitis, significant

hepatocellular injury as evidenced by elevated bilirubin levels (>1. 3), or elevated levels (over 3. 5x normal) of aspartate aminotransferase (AST), and serum glutamic-pyruvic transaminase (SGPT) after the required 3 days of abstinence, or severe renal disease, severe respiratory diseases or severe diarrhea with resulting metabolic acidosis, serum bicarbonate (< 20 mEq/L)

- History of epilepsy or seizure disorder.

- Use of an investigational medication in the 30 days prior to randomization.

- History of nephrolithiasis (kidney stones).

- History of hypersensitivity to topiramate.

- Is female and tests positive on a pregnancy test, is contemplating pregnancy in the

next 6 months, is nursing, or is not using an effective contraceptive method (if relevant). Acceptable methods of contraception include barrier methods (diaphragm or condom with spermicide, intrauterine progesterone contraceptive system, levonorgestrel implant, and medroxyprogesterone acetate contraceptive injection).

- Current use of a carbonic anhydrase inhibitor.

- A history of glaucoma

Kyle M Kampman, MD, Phone: 215-222-3200, Email: kampman_k@mail.trc.upenn.edu

University of Pennsylvania, Treatment Research Center, Philadelphia, Pennsylvania 19104, United States; Recruiting
Donna Simpson, Phone: 215-222-3200, Ext: 158, Email: Simpson_D@mail.trc.upenn.edu

Starting date: September 2004
Ending date: July 2010
Last updated: July 17, 2009