A Phase II Trial of Varenicline for the Treatment of Cocaine Dependence

Study Overview
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Brief Summary
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This is a double-blind placebo-controlled clinical trial (n = 156) of varenicline for the treatment of cocaine dependence that utilizes contingency management to promote treatment attendance.

Detailed Description
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Background: Varenicline is a medication approved for the treatment of Tobacco Use Disorder. It is a partial agonist at α2β4 nicotinic acetyl choline receptors and a full agonist at α7 nicotinic acetyl choline receptors. By its effects on cholinergic activity at α7 and α2β4 receptors, varenicline may reduce dopaminergic and glutamatergic activity in the midbrain, and reduce symptoms of Cocaine Use Disorder. A preliminary trial of varenicline in human cocaine users suggested that varenicline treatment was associated with reductions in cocaine use. The current trial was intended to confirm these promising preliminary results. Methods: This was a 12-week, double blind, placebo controlled parallel group clinical trial involving 156 DSM IV cocaine dependent subjects. Subjects received 2 mg of varenicline or identical placebo each day along with weekly individual cognitive behavioral relapse prevention psychotherapy. The primary outcome measure was cocaine use measured by by thrice weekly urine drug screens. Additional outcome measures included cocaine withdrawal symptoms measured by the Cocaine Selective Severity Assessment (CSSA) End of study cocaine abstinence was analyzed using a Chi-square test.

Official Title
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A Phase II, Randomized, Double-Blind Trial of Varenicline for the Treatment of Cocaine Dependence

Conditions
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Cocaine Dependence

Intervention / Treatment
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* Drug: Varenicline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, 18 to 65 years old. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical Interview for DSM-IV (SCID). Live within a commutable distance of the Treatment Research Center (TRC) at the Penn/VA Center for Studies of Addiction, University of Pennsylvania. We define this to be a distance within the service area of Septa, within an hour drive, or a distance that both the patient and Principal Investigator (PI) find acceptable. Understands and signs the informed consent. Exclusion Criteria: Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, alcohol, or nicotine dependence, as determined by the SCID. Subject is, in the investigator's opinion, at risk of requiring medical detoxification for alcohol dependence during the study. Concomitant treatment with psychotropic medications. Current gambling problems. This will be assessed by the patient's self-report. Patients mandated to treatment based upon a legal decision or as a condition of employment who will use participation in this study to fulfill to their court mandated treatment requirement.This will be assessed by the patient's self-report. Current severe psychiatric symptoms, e.g., psychosis, dementia, suicidal or homicidal ideation, mania or depression requiring antidepressant therapy in the opinion of the Principal Investigator (PI). Use of any investigational medication within the past 30 days. Subject has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis, regional enteritis, or gastrointestinal bleeding) disease. Current use of naltrexone, disulfiram, modafinil, stimulants, haloperidol, benzodiazepines or anticonvulsants. Known hypersensitivity to varenicline. Patients with known AIDS or other serious illnesses that may require hospitalization during the study. Female subjects who are pregnant or lactating, or female subjects of child-bearing potential who are not using acceptable methods of birth control. Acceptable methods of birth control include: barrier (diaphragm or condom) with spermicide intrauterine progesterone contraceptive system levonorgestrel implant medroxyprogesterone acetate contraceptive injection oral contraceptives tubal ligation. Patients with impaired renal function as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986). Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits that are clinically unacceptable to the Medical Director. EKG 1st degree heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Varenicline<br>Oral 1.0 mg BID. | Drug: Varenicline<br> <br> * Other names: Chantix;|
| Placebo Comparator: Placebo<br>Oral 1.0 mg BID. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the Chantix Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial | Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment. | weeks 11,12,13 of the trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator | As measured by average weekly scores for cocaine craving on the brief substance craving scale combining cocaine craving frequency, intensity and duration. Minimum value 0 maximum value 12 higher scores indicate worse craving. | Once per week in weeks 2 through 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cocaine dependence