Efficacy of Varenicline in Methadone-Stabilized Cocaine Users - Full Text View

Sponsor:	Yale University
Collaborators:	National Institute on Drug Abuse (NIDA) Department of Veterans Affairs
Information provided by:	Yale University
ClinicalTrials.gov Identifier:	NCT00567320

Purpose

Cocaine addiction continues to be an important public health problem in the US with a significant cost to the individual and society. Among substance abusers, cocaine use has been recognized as a significant problem especially in methadone-maintenance patients. In several studies, rates of cocaine use have been reported to range from 30 to over 60 percent of those in methadone maintenance programs (Condelli et al. 1991; Hunt et al. 1984; Kidorf and Stitzer 1993; Kosten et al. 1988). In these patients, cocaine use seems to be a predictor of poor clinical outcome (Hartel et al. 1995; Kosten et al. 1987a). The development of effective pharmacotherapies for cocaine use disorders, especially in the opioid-dependent population is of great importance. Unfortunately, such effective pharmacotherapies do not exist.

To determine the safety and tolerability of varenicline in cocaine-using methadone-stabilized subjects.
To determine if varenicline is efficacious in reducing cocaine-use in methadone-stabilized subjects.

Condition	Intervention
Cocaine Addiction	Drug: Varenicline Drug: Sugar pill Drug: to stabilize subjects

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Health Services Research
Official Title:	Efficacy of Varenicline in Methadone-Stabilized Cocaine Users

Resource links provided by NLM:

Drug Information available for: Cocaine hydrochloride Methadone Varenicline Varenicline tartrate Methadone hydrochloride

U.S. FDA Resources

Further study details as provided by Yale University:

Primary Outcome Measures:

We hypothesize that varenicline treatment will decrease cocaine use in methadone-stabilized cocaine users. [ Time Frame: 2 years anticipated ] [ Designated as safety issue: No ]

Enrollment:	30
Study Start Date:	March 2007
Study Completion Date:	August 2009
Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Varenicline	Drug: Varenicline Varenicline up to 2mg a day Other Name: Varenicline
Placebo Comparator: Sugar pill	Drug: Sugar pill Placebo Other Name: Sugar pill
Methadone	Drug: to stabilize subjects Subjects will start at 30mg will be increased as tolerated up to 60mg by end of first week Other Name: Methadone

Detailed Description:

For this pilot study, we hope to recruit a total of 40 subjects, with 20 subjects in the varenicline group, and 20 into the placebo-control group. Assuming significant findings, these data will enable us to estimate a possible effect size for carrying-out a larger study. For preliminary analysis as a prelude to planning larger controlled studies, we will clinically require an effect size of 20% differences in the rates of cocaine positive urines or of self-reported cocaine use between the active medication and placebo groups. We will not adjust for these multiple comparisons to the placebo group since this is a pilot study, and use two-tailed significance level of 0.05 when we employ repeated measures analysis of variance (ANOVA) or HLM (see below) for statistical analysis over the 16-week study period.

An Amendment was made and a new Updated consent form to include new FDA findings for study medication Varenicline." Varenicline may also cause changes in behavior, agitation, depressed mood, suicidal ideation and suicidal behavior." Currently we have 30 subjects who have completed this study. This study is suspended due to these new concerns, Department of Veterans Affairs and the P.I. James Poling agreed.

Study has been published. (April 2011)

Eligibility

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

Criteria

Inclusion Criteria:

Males and females between 18 and 55 years old will be eligible for this study. Females must not be pregnant as determined by pregnancy screening, nor breast feeding, and must be using acceptable birth control methods during study participation.
Current opioid dependence as evidenced by documentation of prior treatment for opioid dependence or signs of withdrawal, self-reported history of opioid dependence for consecutive 12 month period and a positive urine for opiates.
Subjects must fulfill DSM-IV criteria for opioid dependence.
Subjects must have a history of cocaine use, with a reported street cocaine use of a minimum of 1/2 gram during the preceding 30 days.
Subjects must meet DSM-IV criteria for cocaine dependence or abuse, and have laboratory confirmation of recent cocaine use (positive urine for cocaine) during the month prior to study entry.
Subjects must be treatment-seekers for opioid and cocaine use.
Subjects must have smoked at least 10 cigarette per day for at least one year. Varenicline's safety has only been studied in smokers.

Exclusion Criteria:

History of heart disease, left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmia, hypertension.
History of severe renal or hepatic diseases.
History of psychosis, schizophrenia, bipolar or major depressive disorder.
History of seizure disorder.
Current diagnosis of alcohol, benzodiazepine and other drug abuse or dependence (other than opiates, cocaine, and nicotine).
Current use of over-the-counter or prescription psychoactive drugs (antidepressant, anxiolytics, antipsychotics, mood stabilizers, psychostimulants).
Liver function tests (ALT or AST) greater than 3 times normal.
Known allergy to varenicline or methadone.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00567320

Locations

United States, Connecticut
Veterans Hopsital
West Haven, Connecticut, United States, 06516

Sponsors and Collaborators

Yale University

National Institute on Drug Abuse (NIDA)

Department of Veterans Affairs

Investigators

Principal Investigator:

James Poling, Ph.D.

Yale University

More Information

No publications provided by Yale University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Poling J, Rounsaville B, Gonsai K, Severino K, Sofuoglu M. The safety and efficacy of varenicline in cocaine using smokers maintained on methadone: a pilot study. Am J Addict. 2010 Sep;19(5):401-8.

Responsible Party:	James Poling Ph.D., Yale University
ClinicalTrials.gov Identifier:	NCT00567320 History of Changes
Other Study ID Numbers:	MIRECC 000000000, R01DA021264, DPMC, MIRECC 000000000
Study First Received:	December 3, 2007
Last Updated:	April 5, 2011
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Behavior, Addictive
Cocaine-Related Disorders
Compulsive Behavior
Impulsive Behavior
Substance-Related Disorders
Mental Disorders
Methadone
Varenicline
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012