Topiramate for Alcohol and Cocaine Dependence (TOP2)

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

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.

Study Overview

• Status: Completed
• Conditions: Alcoholism; Cocaine Dependence
• Intervention / Treatment: Drug: placebo; Drug: Topiramate

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 (3 months after completing medications).

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Treatment Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and females, 18 years or older.
• Meets DSM(Diagnostic and Statistical Manual)-IV criteria for current diagnoses of cocaine and alcohol dependence, determined by the SCID (Structured Clinical Interview for the DSM)-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 Treatment Research Center (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 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 milliequivalent (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topiramate; topiramate capsules dose titrated up to 300 mg daily	Drug: Topiramate; 300mg/day for 13 weeks; Other Names: topamax
Placebo Comparator: Placebo; placebo capsules identical in appearance to the topiramate capsules	Drug: placebo; placebo pills

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of Participants Abstinent From Cocaine During Last 3 Weeks of 13 Week Trial	Samples were analyzed for benzoylecgonine by fluorescent polarization assay. Samples containing equal to or greater than 300 ng/ml of benzoylecgonine were considered to be positive for cocaine.	Last 3 weeks of 13 week trial
Number of Heavy Drinking Days	Heavy drinking days, defined as more than 4 standard drinks for men and 3 standard drinks for women	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cocaine Withdrawal Symptoms Measured by Cocaine Selective Severity Assessment.	Total cssa score at the end of the medication phase of the trial. The CSSA is a measure of cocaine withdrawal severity. The minimum score is 0 the maximum score is 119. Higher score means more severe cocaine withdrawal symptoms	13 weeks
The Penn Alcohol Craving Scale	This Scale measures alcohol craving. The maximum score is 30, the minimum score is 0. Higher scores are indicative of more severe alcohol craving.	13 weeks

Collaborators and Investigators

• Sponsor: Kyle Kampman
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Kyle M Kampman, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 14, 2005

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: June 23, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: cocaine dependence; Topiramate; alcoholism
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Cocaine-Related Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: 801385; R01AA014657 (U.S. NIH Grant/Contract)