Varenicline and Motivational Advice for Smokers With Substance Use Disorders

Official Title: “Varenicline and Motivational Advice for Smokers With SUD”

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.

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, 6 and 12 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.

Intervention(s) in this Clinical Trial

• Drug: Nicotine Replacement Treatment (NRT)
  • 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.
• Drug: varenicline
  • 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.
• Behavioral: Behavioral counseling for smoking cessation
  • 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.
• Drug: Placebo patch
  • Commercially available matched placebo patches will be used for 12 weeks.
• Drug: Placebo
  • The placebos use identical opaque capsules to the varenicline condition, containing inert filler. Participant takes 1 placebo capsule per day for the first 3 days and 2 per day for 4 days and 12 weeks.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: A
  • Nicotine replacement treatment plus placebo pill
• Active Comparator: B
  • Varenicline plus placebo patches

Primary Measures

• 7-day point-prevalence abstinence
  • Time Frame: Assessed at 3, 6, and 12 months
    Safety Issue?: No

Secondary Measures

• Time to first smoking lapse in days, length of longest continuous abstinence, and percent days abstinent.
  • Time Frame: 1, 4, 8,13, 26, 52 weeks post quit
    Safety Issue?: No

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Brown University Other

Overall Clinical Trial Officials and Contacts

Damaris J Rohsenow, Ph.D. Principal Investigator Brown University  

Overall Contact: Jennifer J Duff, M.A. (401) 863-6667 Jennifer_Larence@brown.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00756275

Study ID Number: 1RO1DA02465201

ClinicalTrials.gov Identifier: NCT00756275

Health Authority: United States: Institutional Review Board