Clinical Trial of Topiramate for Cocaine Addiction

June 9, 2017 updated by: Johns Hopkins University

This is an outpatient clinical trial of topiramate for addressing cocaine dependence and reduction of cocaine associated behaviors in opiate dependent drug users maintained on methadone treatment.

The study aims to answer whether topiramate

  1. is safe and acceptable to methadone patients
  2. reduces cocaine use
  3. helps with collateral problems such as alcohol abuse, tobacco dependence, anxiety, PTSD and/or pain symptoms. The study will also evaluate topiramate effect on neuro-cognitive performance.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an outpatient clinical trial of topiramate treatment for cocaine dependence and reduction of cocaine-associated HIV risk behavior. Topiramate is of high current interest in this regard, having been identified my National Institute on Drud Abuse (NIDA) leadership as among only a small number of tested candidates providing a "positive signal" and warranting further clinical investigation (Vocci, 2005). Topiramate is a marketed antiepileptic that enhances the GABAergic system and antagonizes the glutamatergic system, both new targets in the search for anti-cocaine treatments. A published pilot trial has supported topiramate's efficacy, and it is especially intriguing as potentially beneficial against other disorders prevalent among drug users, such as mood, anxiety, panic disorders, PTSD, pain and cognitive dysfunction, that may contribute to drug use. Design/Methods: This is phase II, double-blind randomized (stratified) 4 group, 2x2 design, evaluating topiramate versus placebo under each of two levels of cocaine-abstinence motivation -- cocaine-abstinence-contingent versus non-contingent voucher incentives. Conduct will be in a methadone maintenance context to ensure adequate retention and adherence, with participants dually dependent on opioids and cocaine. The target topiramate stabilization dose is 300 mg/day (150 mg b.i.d.), with one dose per day being observed at the clinic. The voucher-incentive manipulation provides valuable information about the role of motivation in modulating medication effects; it also provides a positive control condition to document the sensitivity of the study methods for detecting therapeutic benefit. Enrollment will be 300 patients ( 240 completers, 60/group). Participation will be up to 33 weeks - Baseline/Placebo-Run-in (5 weeks), Randomized Medication Treatment (20 weeks, induction, stable dosing, taper), Randomized Voucher Treatment (12 weeks, embedded in Medication period), and Therapeutic Disposition (up to 8 weeks). Data analysis focuses on the 8-week period of stable dosing and concurrent vouchers. The primary outcome variable is days abstinent from cocaine, as determined by a combination of self-report and objective confirmation by quantitative urinalysis toxicology of cocaine metabolite levels and application of the "Preston" rule for determining abstinence. Secondary outcome variables are measures of adverse behaviors and symptoms commonly co-occurring in cocaine abusers (alcohol abuse, tobacco use, depression, anxiety, PTSD, pain, neuro-cognitive and psychomotor performance dysfunction) that may contribute to drug use and/or detrimental effects. Significance: This randomized controlled clinical trial will provide valuable information about the actions and therapeutic effectiveness of the promising candidate anti-cocaine pharmacotherapy topiramate, and about the conditions, correlates, and modulators of any observed effectiveness. It will also provide valuable methodological information contributing to the continuing evolution of clinical trial methods for evaluating potential drug abuse treatment medications.

Study Type

Interventional

Enrollment (Actual)

250

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Behavioral Pharmacology Research Unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18 - 55 years old
  • active opioid and cocaine dependence
  • seeking treatment for cocaine and opioid dependence
  • eligible for methadone maintenance per state and federal regulations
  • able and willing to provide a urine sample thrice a week
  • willing to answer questionnaires on a weekly basis
  • willing to provide breath samples for presence of alcohol thrice weekly
  • fluent in the English language

Exclusion Criteria:

  • allergy to sulfonamide drugs
  • diabetes, respiratory insufficiency, renal tubular acidosis, renal insufficiency, heart failure, liver insufficiency, chronic diarrhea, other chronic diseases predisposing to a risk of acidosis
  • history of nephrolithiasis
  • HIV positive individuals who meet AIDS criteria by CDC criteria or are taking antiretroviral medications
  • serious psychiatric illness (psychosis, dementia)
  • glaucoma or family history of glaucoma
  • prostate hyperplasia, shy bladder, irritable bladder, difficulty providing urine samples on demand
  • female participants: being pregnant, lactating, or unwilling to use an effective method of contraception
  • use of antiepileptic agents
  • benzodiazepine dependence
  • latex allergy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1 topiramate + CR
topiramate and contingency reinforcement for urine sample confirming cocaine abstinence
Drug: topiramate

topiramate powder 0mg - 150 mg with lactate in blind capsules. Two capsules dispensed daily. One capsule ingested under supervision at the methadone window. One capsule to be ingested at home at bedtime. Participant is expected to return the empty blister pack on the following day.

capsules are administered from week 4 through 25 of the trial

Other Names:
  • topamax®
  • CAS 97240-79-4
Behavioral: Contingency Reinforcement
monetary reward for self-reported cocaine abstinence confirmed by urine toxicology results
Other Names:
  • contingency management
Experimental: 2 topiramate + NonCR
Topiramate and random reinforcement irrespective of cocaine use
Drug: topiramate

topiramate powder 0mg - 150 mg with lactate in blind capsules. Two capsules dispensed daily. One capsule ingested under supervision at the methadone window. One capsule to be ingested at home at bedtime. Participant is expected to return the empty blister pack on the following day.

capsules are administered from week 4 through 25 of the trial

Other Names:
  • topamax®
  • CAS 97240-79-4
Placebo Comparator: 4 Placebo + NonCR
Drug: placebo + NonCR
participant receives placebo capsules and monetary reinforcers by chance, irrespective of cocaine use or abstinence
Active Comparator: 3 Placebo + CR
Placebo and contingency reinforcement for urine sample confirming cocaine abstinence
Behavioral: Contingency Reinforcement
monetary reward for self-reported cocaine abstinence confirmed by urine toxicology results
Other Names:
  • contingency management

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of Cocaine Positive Urine Samples Per Treatment Condition
Time Frame: Urine samples collected 3 times weekly from week 1 through 26
Percentage of cocaine positive urine samples as measured by Preston new use rule (50% reduction in cocaine metabolites from previous urine)
Urine samples collected 3 times weekly from week 1 through 26

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Voucher Earnings
Time Frame: 12 weeks (Weeks 8-20)

Voucher earnings used as a measurement of contigency management (CM) or operate conditioning. Volunteers were rewarded vouchers of escalating monetary value for cocaine abstinence, as indicated by a cocaine negative urine sample. The first cocaine negative urine earned a $2.50 voucher, and the value increased by $1.50 for each subsequent cocaine negative sample. Volunteers were awarded a bonus of $10.00 for every three consecutive cocaine negative urine samples. Urine samples were collected 3 times per week, and vouchers were attainable between Weeks 8 and 20.

Contingency management as a measurement of operant conditioning in which positive reinforcement is applied (in this case vouchers of monetary value) and cocaine abstinence
12 weeks (Weeks 8-20)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Annie Umbricht, M.D., Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2007

Primary Completion (Actual)

June 1, 2011

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

May 23, 2008

First Submitted That Met QC Criteria

May 27, 2008

First Posted (Estimate)

May 28, 2008

Study Record Updates

Last Update Posted (Actual)

July 11, 2017

Last Update Submitted That Met QC Criteria

June 9, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01DA021808 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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