Varenicline and Motivational Advice for Smokers With Substance Use Disorders

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effects of 12 weeks of varenicline as compared to nicotine replacement therapy for smoking cessation among outpatients in treatment for substance use disorders. The intervention also incorporates counseling (Brief Advice), (adapted for sobriety settings), skills training and medication management.

Detailed Description
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People with substance use disorders (SUD) have a high prevalence and rate of smoking with little success in quitting, so stronger approaches are needed to encourage attempts to quit smoking. Brief advice (BA), to motivate cessation, produced some benefit but low abstinence rates for smokers with SUDs while adding free transdermal nicotine replacement therapy (NRT) improved short-term cessation rates. Varenicline has been found to produce higher rates of short and long-term abstinence than bupropion or placebo. However, a comparison between the efficacy of varenicline and NRT has not yet conducted with people with SUDs. Given the lack of effectiveness for standard smoking treatments for this population, what needs to be known is whether varenicline would increase the smoking abstinence rates relative to NRT when all receive motivational counseling. The primary aim of this study is to evaluate the effects of 12 weeks of varenicline as compared to NRT, using a two-group randomized placebo-controlled design on smoking cessation rates for 12 months among 274 outpatients in treatment for SUD. The counseling incorporates BA (adapted slightly for sobriety settings by directly addressing barriers and concerns expressed by substance abusers), skills training and medication management. Confirmed point-prevalence and sustained abstinence will be assessed at 3 and 6 a months after the start of treatment. Secondary aims will examine potential mediators of effect including within-treatment abstinence, craving, and nicotine withdrawal levels. The potential significance is to add to knowledge about the most effective ways to maximize smoking cessation among substance abusers, important given that no methods are known to work with this difficult population. No study published to date has compared varenicline to NRT for efficacy with patients with SUD.

Official Title
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Varenicline and Motivational Advice for Smokers With SUD

Conditions
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Smoking Cessation, Nicotine Dependence

Intervention / Treatment
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* Drug: Nicotine Replacement Treatment (NRT)
* Drug: varenicline
* Behavioral: Behavioral counseling for smoking cessation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of substance abuse or dependence by DSM-IV criteria Currently smoking at least 10 cigarettes per day for the past 6 months Exclusion Criteria: Active psychosis or marked organic impairment according to medical records, or evidence of hallucinations or delusions Current use of any nicotine replacement, or other smoking cessation treatment Medical contraindications for NRT (including pregnancy, nursing, women not using birth control during heterosexual sex, history of unstable angina, history of severe congestive heart failure, uncontrolled hypertension, lung cancer, supplemental oxygen, allergy to adhesive, severe skin disease that requires treatment) Medical contraindications for VAR (including pregnancy, nursing, severe renal impairment by laboratory test, history of intolerance of varenicline, history of serious suicidal ideation or attempts in the past 5 years)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: Nicotine Replacement + PLA pill<br>Nicotine replacement treatment patch plus matched placebo pill | Drug: Nicotine Replacement Treatment (NRT)<br>* Nicotine replacement treatment (NRT) will follow the clinical practice guidelines for nicotine patch for people smoking at least 10 cigarettes per day (USDHHS, 2000), modified to allow 12 weeks use (tapering recommended for people with AUDs by Hughes et al., 2003b): 21 mg/day for 4 weeks, 14 mg/day for 4 weeks, 7 mg/day for 4 weeks.<br>* Other names: NRT;Behavioral: Behavioral counseling for smoking cessation<br>* The counseling consists of 10 sessions of Brief Advice (BA).BA is a simple smoking cessation counseling strategy: Assess smoking and initial interest in cessation, advise patient to quit smoking, assist patient in quitting, discussion of sobriety specific concerns, and cognitive-behavioral skills training. Medication management is conducted in every session, smoking cessation pamphlets are available. Session 1 (60 min, in-person) will be 1 week before Quit Day.Session 2 (30 min, in-person) takes place on Quit Day. Session 3 (10 min, in-person) will be 1 week later. Sessions 4-10 will be 5-10 min. telephone contacts at Weeks 2, 3, 4, 6, 8, 10, and 12 after Quit Day.<br>* Other names: Behavioral treatment for quitting;|
| Active Comparator: Varenicline + PLA patch<br>Varenicline plus matched placebo patches containing no nicotine | Drug: varenicline<br>* Varenicline (VAR, 2 mg/d in divided doses) will be administered as follows. VAR: participant takes 0.5 mg/d for the first 3 days, 1 mg/d (0.5 mg 2x/d) for the next 4 days, and 2mg/d (1.0mg 2x/d) for 12 weeks.<br>* Other names: Chantix;Behavioral: Behavioral counseling for smoking cessation<br>* The counseling consists of 10 sessions of Brief Advice (BA).BA is a simple smoking cessation counseling strategy: Assess smoking and initial interest in cessation, advise patient to quit smoking, assist patient in quitting, discussion of sobriety specific concerns, and cognitive-behavioral skills training. Medication management is conducted in every session, smoking cessation pamphlets are available. Session 1 (60 min, in-person) will be 1 week before Quit Day.Session 2 (30 min, in-person) takes place on Quit Day. Session 3 (10 min, in-person) will be 1 week later. Sessions 4-10 will be 5-10 min. telephone contacts at Weeks 2, 3, 4, 6, 8, 10, and 12 after Quit Day.<br>* Other names: Behavioral treatment for quitting;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point-prevalence Smoking Abstinence | 7 -day smoking cessation confirmed by expired alveolar CO levels of < 10 ppm or salivary cotinine < 16 ng/ml. | 3 month follow up | 
| 7-day Point-prevalence Smoking Abstinence | 7 -day smoking cessation confirmed by expired alveolar CO levels of < 10 ppm or salivary cotinine < 16 ng/ml. | 6 month follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Longest Continuous Abstinence |  | Weeks 9 to 12 | 
| Percent Smoking Days |  | 3 month follow up | 
| Percent Smoking Days |  | 6 month follow up | 
| Percent Relapsed to Drug Use |  | 3 month follow up | 
| Percent Relapsed to Drug Use |  | 6 month follow up | 
| Percent Relapsed to Any Heavy Drinking | 6 or more drinks for men; 5 or more drinks for women | 3 month follow up | 
| Percent Relapsed to Any Heavy Drinking | 6 or more drinks for men; 5 or more drinks for women | 6 month follow up | 
| Beck Depression Inventory | 0-10 = These ups and downs are considered normal 11-16 = Mild mood disturbance 17-20 = Borderline clinical depression 21-30 = Moderate depression 31-40 = Severe depression over 40 = Extreme depression | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tobacco Smoking, Smoking Cessation, Nicotine Dependence, Tobacco Use Disorder