Genetically Informed Smoking Cessation Trial (GISC)

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation
• Intervention / Treatment: Drug: Placebo; Drug: Varenicline; Drug: Combination NRT (Nicotine patch, Nicotine lozenge); Behavioral: Intensive smoking counseling

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.

• Study Type: Interventional
• Enrollment (Actual): 822
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult (≥21 years of age), seeking treatment for smoking cessation.
2. Able to speak English,
3. Active smoking (Cigarettes Per Day (CPD) ≥5), and exhaled Carbon Monoxide (CO) ≥8 ppm
4. Agree to participate in this randomized smoking cessation trial with follow up assessments up to 12 months.

Exclusion Criteria:

1. Pregnancy or breast feeding,
2. 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,
3. Allergy to nicotine patch, lozenge, or varenicline,
4. Unwillingness to prevent pregnancy during the medication phase and 1 month afterwards (women only),
5. Significant cardiac conditions (myocardial infarction, unstable angina, coronary angioplasty, cardiac bypass) or serious arrhythmia in past 6 months,
6. Current heavy alcohol consumption (≥6 drinks/day, 6 days/week),
7. Active psychosis or poorly controlled depression within the past 6 months,
8. Any prior suicide attempt or suicidal ideation within the past 6 months,
9. End stage renal disease with hemodialysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Combination NRT and 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.	Drug: Combination NRT (Nicotine patch, Nicotine lozenge); Other Names: Nicoderm CQ; Nicotine Polacrilex Lozenge; Behavioral: Intensive smoking counseling
Active Comparator: Varenicline (Chantix) and 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.	Drug: Varenicline; Other Names: Chantix; Behavioral: Intensive smoking counseling
Placebo Comparator: Placebo Medicine and 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.	Drug: Placebo; Behavioral: Intensive smoking counseling

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Institute on Drug Abuse (NIDA); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Li-Shiun Chen, M.D., Washington University School of Medicine

Publications and helpful links

General Publications

• Chen LS, Baker TB, Miller JP, Bray M, Smock N, Chen J, Stoneking F, Culverhouse RC, Saccone NL, Amos CI, Carney RM, Jorenby DE, Bierut LJ. Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a Randomized Placebo-Controlled Trial. Clin Pharmacol Ther. 2020 Dec;108(6):1315-1325. doi: 10.1002/cpt.1971. Epub 2020 Aug 4.

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2015
• Primary Completion (Actual): December 26, 2018
• Study Completion (Actual): August 31, 2019

Study Registration Dates

• First Submitted: January 26, 2015
• First Submitted That Met QC Criteria: January 29, 2015
• First Posted (Estimate): January 30, 2015

Study Record Updates

• Last Update Posted (Actual): September 22, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Counseling; Smoking cessation; Genetics and Genomics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine; Varenicline
• Other Study ID Numbers: 201305128; 1R01DA038076-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No