Genetically Informed Smoking Cessation Trial

Phase 4

Completed

Conditions: Smoking Cessation

Interventions: Drug: Combination NRT (Nicotine patch, Nicotine lozenge)
Drug: Varenicline
Drug: Placebo
Behavioral: Intensive smoking counseling

Registration Number: NCT02351167

Lead Sponsor: Washington University School of Medicine

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 822

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination NRT and Counseling	Combination NRT (Nicotine patch, Nicotine lozenge)	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.
Combination NRT and Counseling	Intensive smoking counseling	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.
Varenicline (Chantix) and Counseling	Varenicline	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.
Varenicline (Chantix) and Counseling	Intensive smoking counseling	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.
Placebo Medicine and Counseling	Placebo	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.
Placebo Medicine and Counseling	Intensive smoking counseling	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.

Primary Outcome Measures

Name	Time	Method
7-day Point Prevalence Quit Rate	Week 12	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.

Secondary Outcome Measures

Name	Time	Method
Continuous Abstinence	12 weeks (with first 1 week initial grace period)	The definition of this measure requires: Not taking even 1 cigarette puff from target quit date to end of treatment.
7-day Point Prevalence Quit Rate	Week 24	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.
Number of Days to Lapse	Assessed from the target quit day through 52 weeks	* 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
Number of Days to Relapse	Assessed from the target quit day through 52 weeks	* 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
Initial Cessation	Assessed for the first seven days after the target quit date	Defined as at least 1 day of abstinence during the first 7 days after the target quit day.
Longitudinal Models of Abstinence Outcomes Across Multiple Time Points	0-52 Weeks	-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.
Longitudinal Models of Smoking Quantity in Cigarettes Per Day Outcomes Across Multiple Time Points.	0-52 Weeks	The definition of this measure requires self-reported cigarettes per day.
Medication Adherence	Pre-quit week to Week 12	Adherence is the proportion of expected medication (varenicline, patch, lozenge) taken as advised during pre-quit week to week 12
Side Effects	Pre-quit week to Week 12	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.
Withdrawal	Pre-quit, quit, week 1, week 2, and week 4	* 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.