Clinical trial NCT00685178: Clinical Trial of Topiramate for Cocaine Addiction
Official title: Clinical Trial of Topiramate for Cocaine Addiction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: addiction
drug dependence
stimulant
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2008-05-28
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Proportion of Cocaine Positive Urine Samples Per Treatment Condition
timeFrame: Urine samples collected 3 times weekly from week 1 through 26
Secondary outcomes:
measure: Voucher Earnings
timeFrame: 12 weeks (Weeks 8-20)
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Behavioral Pharmacology Research Unit
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Annie Umbricht, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Umbricht A, DeFulio A, Winstanley EL, Tompkins DA, Peirce J, Mintzer MZ, Strain EC, Bigelow GE. Topiramate for cocaine dependence during methadone maintenance treatment: a randomized controlled trial. Drug Alcohol Depend. 2014 Jul 1;140:92-100. doi: 10.1016/j.drugalcdep.2014.03.033. Epub 2014 Apr 16.