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

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Combination of Scheduled Reduced Smoking With Varenicline to Enhance Cessation

Conditions
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Nicotine Addiction

Intervention / Treatment
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* Other: Scheduled Gradual Reduction + Varenicline
* Other: Scheduled Gradual Reduction + Placebo Drug
* Other: Basic Advice + Varenicline
* Other: Basic Advice + Placebo Drug


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Scheduled Gradual Reduction + Varenicline<br>Participants will be given the behavioral intervention of Scheduled Gradual Reduction along with the smoking cessation drug, Varenicline. | Other: Scheduled Gradual Reduction + Varenicline<br>* Participants will receive a four-week Scheduled Gradual Reduction (SGR) intervention in which participants cut down on the number of cigarettes smoked. This is done through a smoking schedule in which participants smoke a cigarette at given fixed and equal intervals throughout their waking day. Additionally, they will take 0.5 mg of Varenicline (VN) once a day for the first three days, then 0.5 mg twice a day for the next four days, and they will continue for 13 weeks at 1.0 mg twice per day.<br>|
| Experimental: Scheduled Gradual Reduction + Placebo Drug<br>Participants will be given the behavioral intervention, SGR, along with a placebo drug matching the schedule of the VN group. | Other: Scheduled Gradual Reduction + Placebo Drug<br>* Participants will receive a four-week Scheduled Gradual Reduction (SGR) intervention in which participants cut down on the number of cigarettes smoked. This is done through a smoking schedule in which participants smoke a cigarette at given fixed and equal intervals throughout their waking day. Additionally, they will take placebo pills matching the schedule of the VN group.<br>|
| Experimental: Basic Advice + Varenicline<br>Participants will be given basic advice about quitting smoking along with the smoking cessation drug Varenicline | Other: Basic Advice + Varenicline<br>* Participants will receive informational pamphlets with advice about quitting smoking. Additionally, they will take 0.5 mg of Varenicline (VN) once a day for the first three days, then 0.5 mg twice a day for the next four days, and they will continue for 13 weeks at 1.0 mg twice per day.<br>|
| Placebo Comparator: Basic Advice + Placebo Drug<br>Participants will be given basic advice along with a placebo drug matching the schedule of the VN group. | Other: Basic Advice + Placebo Drug<br>* Participants will receive informational pamphlets with advice about quitting smoking. Additionally, they will take placebo pills matching the schedule of the VN group.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Prolonged Abstinence | Prolonged Abstinence from 12 weeks post-quit as compared to 4 weeks post-quit | up to12 weeks post-quit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Continuous Abstinence | Continuous Abstinence as compared from 30 days post-quit to 30 days post end-of-treatment | 30 days post-quit and 30 days post end-of-treatment | 
| Comparison of Survival | Survival as compared from 30 days post-quit to 30 days post end-of-treatment | 30 days post-quit and 30 days post end-of-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking, cigarette, cessation, varenicline, scheduled reduction, craving