Clinical Trial of Topiramate for Cocaine Addiction

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Annie Umbricht, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00685178
First received: May 23, 2008
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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.

Condition Intervention Phase
Cocaine Dependence
Drug: topiramate
Behavioral: Contingency Reinforcement
Drug: placebo + NonCR
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Trial of Topiramate for Cocaine Addiction

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • proportion of subjects achieving 3 consecutive weeks of cocaine abstinence as measured by urine samples free of cocaine metabolites [ Time Frame: Urine samples collected 3 times weekly from week 1 through 26 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • symptom checklist [ Time Frame: weekly ] [ Designated as safety issue: Yes ]

Enrollment: 250
Study Start Date: February 2007
Study Completion Date: September 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: contingency management

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00685178

Locations
United States, Maryland
Behavioral Pharmacology Research Unit
Baltimore, Maryland, United States, 21224
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Annie Umbricht, M.D. Johns Hopkins University
  More Information

No publications provided

Responsible Party: Annie Umbricht, Assistant Professor, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00685178     History of Changes
Other Study ID Numbers: R01DA021808, R01DA021808
Study First Received: May 23, 2008
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johns Hopkins University:
addiction
drug dependence
stimulant

Additional relevant MeSH terms:
Behavior, Addictive
Cocaine-Related Disorders
Compulsive Behavior
Impulsive Behavior
Substance-Related Disorders
Mental Disorders
Cocaine
Topiramate
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Uptake Inhibitors
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Uptake Inhibitors
Physiological Effects of Drugs
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anticonvulsants
Neuroprotective Agents
Protective Agents
Anti-Obesity Agents

ClinicalTrials.gov processed this record on April 23, 2014