Clinical Trial of Topiramate for Cocaine Addiction

Phase 2

Completed

Conditions: Cocaine Dependence

Interventions: Drug: topiramate
Drug: placebo + NonCR
Behavioral: Contingency Reinforcement

Registration Number: NCT00685178

Lead Sponsor: Johns Hopkins University

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 250

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1 topiramate + CR	topiramate	topiramate and contingency reinforcement for urine sample confirming cocaine abstinence
1 topiramate + CR	Contingency Reinforcement	topiramate and contingency reinforcement for urine sample confirming cocaine abstinence
4 Placebo + NonCR	placebo + NonCR	-
3 Placebo + CR	Contingency Reinforcement	Placebo and contingency reinforcement for urine sample confirming cocaine abstinence
2 topiramate + NonCR	topiramate	Topiramate and random reinforcement irrespective of cocaine use

Primary Outcome Measures

Name	Time	Method
Proportion of Cocaine Positive Urine Samples Per Treatment Condition	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)

Secondary Outcome Measures

Name	Time	Method
Voucher Earnings	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