A Smoking Intervention Study Using Scheduled Gradual Reduction With Varenicline to Help With Cessation

Phase 4

Terminated

• Conditions: Nicotine Addiction
• Interventions: Other: Basic Advice + Placebo Drug; Other: Scheduled Gradual Reduction + Varenicline; Other: Basic Advice + Varenicline; Other: Scheduled Gradual Reduction + Placebo Drug

• Registration Number: NCT01772641
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary

This study has three main aims. Aim 1: To provide initial data on the efficacy of combined Scheduled Gradual Reduction (SGR) and Varenicline (VN) for smoking cessation, by assessing abstinence and levels of smoking at 2 time points (4 and 12 weeks post quit). Aim 2: To explore the possibility that SGR+VN will be particularly efficacious among smokers with higher background levels of Cue Reactivity (CR), as assessed at the start of the study, using a classic experimental smoking CR paradigm. Aim 3: To explore possible mechanisms underlying the effects of SGR+VN, by assessing potential mediators (i.e., self-efficacy, cue-induced cravings) of treatment effects.

Detailed Description

Smoking remains an intransigent public health concern. There is ample evidence that non-pharmacological factors, such as environmental triggers (e.g., sight or smell of a cigarette), can give rise to strong classically-conditioned urges to smoke (termed 'cue-reactivity' \[CR\]), and that exposure to smoking cues can contribute to cessation failure. One promising intervention that may address CR is scheduled smoking with gradual reduction (SGR). Under SGR, individuals smoke only at fixed intervals, and over several weeks, systematically decrease their cigarettes consumed each day. The approach is postulated to: 1) provide 'practice' coping with environmentally-triggered cravings that occur during the inter-cigarette intervals, yielding increased self-efficacy to quit, and 2) weaken the associations between cues and smoking. Accumulating evidence has also shown that the smoking cessation drug, varenicline (VN), substantially ameliorates cravings and enhances cessation, significantly outperforming other drugs. Interestingly, recent animal research suggests that VN may operate at least partially by dampening conditioned drug cravings. A combination therapy consisting of SGR+VN might thus lead to significantly enhanced cessation, simultaneously attacking cravings using both pharmacological and non-pharmacological approaches. Because the beneficial effects of SGR and VN may be at least partially due to enhanced management of conditioned cravings, it is possible that that they will be particularly efficacious for smokers with high levels of CR. Using both laboratory experimental techniques and a prospective intervention design in this R34 application, we propose to provide initial data to: 1) test the hypothesis that a combination of SGR+VN will enhance cessation, 2) explore the possibility that SGR and VN might be particularly efficacious among smokers with higher levels of CR, and 3) explore potential mechanisms underlying treatment effects. Findings from this study would set the stage for larger efficacy and effectiveness trials of SGR alone and in conjunction with VN, as well as efforts to target SGR and/or VN toward the subgroups that would benefit the most (e.g., smokers with high levels of CR, carriers of specific smoking-related genotypes).

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2013-01-17
• Study First Submitted QC: 2013-01-18
• Study First Posted: 2013-01-21
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-14
• Last Update Posted: 2016-03-16

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Current cigarette smoker
• Averages at least 10 cigarettes/day for 5 or more years
• DSM-IV diagnosis of Nicotine Dependence
• Breath carbon monoxide > 6 ppm
• Motivated to quit: score > 8 on Contemplation Ladder
• Age > 18 years

Exclusion Criteria

• Current illicit substance use
• Other tobacco use (e.g., cigar, pipe)
• History of psychosis
• Past or current cardiovascular disease
• Impaired renal functioning
• Pregnancy
• Nursing
• Current treatment for smoking cessation
• Clinically significant depressive symptoms (CES-D > 16)
• Current suicidal ideation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Basic Advice + Placebo Drug	Basic Advice + Placebo Drug	Participants will be given basic advice along with a placebo drug matching the schedule of the VN group.
Scheduled Gradual Reduction + Varenicline	Scheduled Gradual Reduction + Varenicline	Participants will be given the behavioral intervention of Scheduled Gradual Reduction along with the smoking cessation drug, Varenicline.
Basic Advice + Varenicline	Basic Advice + Varenicline	Participants will be given basic advice about quitting smoking along with the smoking cessation drug Varenicline
Scheduled Gradual Reduction + Placebo Drug	Scheduled Gradual Reduction + Placebo Drug	Participants will be given the behavioral intervention, SGR, along with a placebo drug matching the schedule of the VN group.

Primary Outcome Measures

Name	Time	Method
Comparison of Prolonged Abstinence	up to12 weeks post-quit	Prolonged Abstinence from 12 weeks post-quit as compared to 4 weeks post-quit

Secondary Outcome Measures

Name	Time	Method
Comparison of Continuous Abstinence	30 days post-quit and 30 days post end-of-treatment	Continuous Abstinence as compared from 30 days post-quit to 30 days post end-of-treatment
Comparison of Survival	30 days post-quit and 30 days post end-of-treatment	Survival as compared from 30 days post-quit to 30 days post end-of-treatment

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States