Genetically Informed Smoking Cessation Trial

Study Overview
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Brief Summary
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The investigators' goal is to identify the most appropriate smoking cessation treatments for smokers based on genetic information. Smokers try to quit smoking but relapses are common.

Detailed Description
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The investigators' goal is to determine whether genetic markers can be used to optimize smoking cessation pharmacotherapy to enhance efficacy, medication adherence, and reduce side effects. Smoking is a leading cause of preventable death and disability, and smoking cessation reverses the risk of mortality. However, cessation failure is common despite available cessation medications, which are associated with different efficacy, side effects, adherence, use constraints, and costs. This challenge can be addressed by improving current treatments via personalized medicine based on individual genetic markers to maximize efficacy and minimize side effects. The investigators propose a prospective, genotype-based stratified randomization trial to compare two smoking cessation medications (combination NRT [patch and lozenge], varenicline vs. placebo) for 3 months in 720 smokers with known genotypes.

Official Title
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Genetically Informed Smoking Cessation Trial

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Combination NRT (Nicotine patch, Nicotine lozenge)
* Drug: Varenicline
* Drug: Placebo
* Behavioral: Intensive smoking counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥21 years of age), seeking treatment for smoking cessation. Able to speak English, Active smoking (Cigarettes Per Day (CPD) ≥5), and exhaled Carbon Monoxide (CO) ≥8 ppm Agree to participate in this randomized smoking cessation trial with follow up assessments up to 12 months. Exclusion Criteria: Pregnancy or breast feeding, Active use or recent use (< or equal to 1 month) of medication or e-cigarettes for nicotine dependence/smoking cessation, or use of e-cigarettes for more than 9 days in the prior month, Allergy to nicotine patch, lozenge, or varenicline, Unwillingness to prevent pregnancy during the medication phase and 1 month afterwards (women only), Significant cardiac conditions (myocardial infarction, unstable angina, coronary angioplasty, cardiac bypass) or serious arrhythmia in past 6 months, Current heavy alcohol consumption (≥6 drinks/day, 6 days/week), Active psychosis or poorly controlled depression within the past 6 months, Any prior suicide attempt or suicidal ideation within the past 6 months, End stage renal disease with hemodialysis.

Ages Eligible for Study
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Minimum Age: 21 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Combination NRT and Counseling<br>Combination Nicotine replacement therapy (cNRT) (patch and lozenge) and smoking cessation counseling will be provided to participants. Lozenges will be given for 12 weeks with a 1 week pre-quit titration and patch for 12 weeks. Seven smoking counseling sessions will be given during treatment. | Drug: Combination NRT (Nicotine patch, Nicotine lozenge)<br> <br> * Other names: Nicotine Polacrilex Lozenge;Behavioral: Intensive smoking counseling<br> <br> |
| Active Comparator: Varenicline (Chantix) and Counseling<br>Varenicline (pill) and smoking cessation counseling will be provided to participants for 12 weeks with 1 week pre-quit titration. Seven smoking cessation counseling sessions will be given during treatment. | Drug: Varenicline<br> <br> * Other names: Chantix;Behavioral: Intensive smoking counseling<br> <br> |
| Placebo Comparator: Placebo Medicine and Counseling<br>Placebo pill and smoking cessation counseling will be provided to participants for 12 weeks with 1 week pre-quit titration. Placebo lozenges will be given for 12 weeks with a 1 week pre-quit titration and patch for 12 weeks. Seven smoking counseling sessions will be given during treatment. | Drug: Placebo<br> <br> Behavioral: Intensive smoking counseling<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point Prevalence Quit Rate | The definition of this measure requires: (a) no self-reported smoking (not even a puff of a cigarette) for at least the 7 days prior to the assessment, and (b) biochemical verification of abstinence. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Continuous Abstinence | The definition of this measure requires: Not taking even 1 cigarette puff from target quit date to end of treatment. | 12 weeks (with first 1 week initial grace period) | 
| 7-day Point Prevalence Quit Rate | The definition of this measure requires: (a) no self-reported smoking (not even a puff of a cigarette) for at least the 7 days prior to the assessment, and (b) biochemical verification of abstinence. | Week 24 | 
| Number of Days to Lapse | The number of days to lapse is defined as the number of days from the target quit date until the participant reports smoking (even a single puff). Participants who did not lapse by the end of the 52 weeks and participants who had missing information on lapse are not included in the overall number of participants analyzed | Assessed from the target quit day through 52 weeks | 
| Number of Days to Relapse | The number of days to relapse is defined as the number of days from the target quit day until the first of seven consecutive days of smoking. Participants who did not relapse by the end of the 52 weeks and participants who had missing information on relapse are not included in the overall number of participants analyzed | Assessed from the target quit day through 52 weeks | 
| Initial Cessation | Defined as at least 1 day of abstinence during the first 7 days after the target quit day. | Assessed for the first seven days after the target quit date | 
| Longitudinal Models of Abstinence Outcomes Across Multiple Time Points | -The definition of this measure requires; no self-reported smoking (not even a puff of a cigarette) for at least 7 days prior to the assessment. | 0-52 Weeks | 
| Longitudinal Models of Smoking Quantity in Cigarettes Per Day Outcomes Across Multiple Time Points. | The definition of this measure requires self-reported cigarettes per day. | 0-52 Weeks | 
| Medication Adherence | Adherence is the proportion of expected medication (varenicline, patch, lozenge) taken as advised during pre-quit week to week 12 | Pre-quit week to Week 12 | 
| Side Effects | All reported side effects (occurring>4%) will be summarized and presented for the study. In addition, the investigators will further identify a pre-specified set of key side effects as being related to drug agonist effects (e.g., nausea, vomiting, racing heart, headache, and sleep disturbance). These will be analyzed as rate of occurrence during the period of medication use. | Pre-quit week to Week 12 | 
| Withdrawal | Withdrawal severity is assessed by Wisconsin Smoking Withdrawal Scale (WSWS), there are 28 items. Participants rate each item on a scale of 0-4 (0=Strongly disagree, 1=Disagree, 2=Feel neutral, 3=Agree, 4=Strongly agree). The subscale to each item is determined on how high they agree on the scale. For some items, the subscale is determined on how low they agreed. Each score is determined by the mean of each item that applies. Higher means indicate greater withdrawal. The scores were calculated by averaging a mean score of each item for each participant with data from time point pre-quit, quit, week 1, week 2, and week 4. The mean score for each participant was averaged for each item and a mean score was taken for each treatment condition (cNRT, Varenicline, Placebo). These data are reported as mean withdrawal scores and not change in withdrawal scores. | Pre-quit, quit, week 1, week 2, and week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking cessation, Counseling, Genetics and Genomics