Clinical trial NCT01680887: A Phase II Trial of Varenicline for the Treatment of Cocaine Dependence
Official title: A Phase II, Randomized, Double-Blind Trial of Varenicline for the Treatment of Cocaine Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cocaine Dependence
Keywords: Cocaine dependence
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2012-09-07
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Males and females, 18 to 65 years old.
2. Meets DSM-IV criteria for Cocaine Dependence, as determined by the Structured Clinical Interview for DSM-IV (SCID).
3. 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.
4. Understands and signs the informed consent.

Exclusion Criteria:

1. Current DSM-IV diagnosis of any psychoactive substance dependence other than cocaine, alcohol, or nicotine dependence, as determined by the SCID.
2. Subject is, in the investigator's opinion, at risk of requiring medical detoxification for alcohol dependence during the study.
3. Concomitant treatment with psychotropic medications.
4. Current gambling problems. This will be assessed by the patient's self-report.
5. 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.
6. 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).
7. Use of any investigational medication within the past 30 days.
8. Subject has serious heart, lung, kidney, immune system, GI tract (ulcerative colitis, regional enteritis, or gastrointestinal bleeding) disease.
9. Current use of naltrexone, disulfiram, modafinil, stimulants, haloperidol, benzodiazepines or anticonvulsants.
10. Known hypersensitivity to varenicline.
11. Patients with known AIDS or other serious illnesses that may require hospitalization during the study.
12. 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:

    1. barrier (diaphragm or condom) with spermicide
    2. intrauterine progesterone contraceptive system
    3. levonorgestrel implant
    4. medroxyprogesterone acetate contraceptive injection
    5. oral contraceptives
    6. tubal ligation.
13. Patients with impaired renal function as indicated by corrected creatinine clearance below 60 ml/min as determined by the modified Cockcroft equation (CDC, 1986).
14. 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).

Primary outcomes:
measure: 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
timeFrame: weeks 11,12,13 of the trial
Secondary outcomes:
measure: Average Weekly Cocaine Craving Scores Varenicline Group Versus the Placebo Group Comparator
timeFrame: Once per week in weeks 2 through 13
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania Treatment Research Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Kyle M Kampman, MD
role: PRINCIPAL_INVESTIGATOR
References: