Study 35 – Genetically Informative Smoking Cessation Trial

Investigator:  Li-Shiun Chen

Release Date:  10/23/2018: processing

Purpose of the study: The goal of this genetically informed randomized smoking cessation trial is to identify the most appropriate smoking cessation treatments for smokers based on genetic information.

Background: In a general population sample of smokers seeking to quit, we recently discovered that genetic markers in the CHRNA5 gene predict cessation success and response to pharmacotherapy. Patients with the high-risk variants had a 3-fold enhanced response to pharmacotherapy as compared to those with the low-risk and intermediate-risk variants. This genetically informed treatment study will investigate how genetic information can be used to personalize cessation pharmacotherapy to maximize efficacy for patients.

Methods: This randomized controlled trial will recruit 720 participants from a previous study who agreed to be contacted again to participate in a smoking cessation trial. These participants also previously provided a DNA sample for genetic analysis as part of that study. Participants who are actively nicotine dependent and meet the inclusion/exclusion criteria will be randomly assigned to receive combination Nicotine Replacement Therapy (i.e., the nicotine patch and nicotine lozenge), varenicline, or placebo (patch/lozenge, or pill) for 3 months. All participants will receive intensive smoking cessation counseling for 3 months during treatment. In addition, each participant will provide a blood sample of 15ml which will be used to look at genes related to nicotine metabolism and other genetic markers. These samples are sent to the GISC cell repository located at Rutgers University. Participants will complete questionnaires and interviews assessing smoking history, environmental history, demographics, nicotine dependence, sadness, anxiety, anger, craving, hunger, sleep, disease status, adverse events, and health history. All measures will be administered via computer by trained research assistants over the course of one year.

Analysis: We will examine the main effects of medication (combination NRT vs. varenicline vs. placebo) and genotype (high, intermediate, and low risk), as well as the pharmacogenetic interaction between genotype and medication on the primary cessation outcome (abstinence at end of treatment, ABST_EOT) and other outcomes (abstinence at 6 months). We chose the primary efficacy measure of abstinence at 3 months (EOT) because preliminary data (Chen et al., 2012) suggest the genetic effects on cessation take place in the early cessation stage. Our hypothesis is that NRT significantly increases smoking abstinence in patients possessing high-risk haplotypes, but not amongst patients without such haplotypes. This experiment will answer the following questions: 1) Does combination NRT improve cessation outcome (ABST_EOT) relative to placebo? 2) Is there a genotype X Pharmacotherapy interaction with regard to abstinence? 3) Does varenicline  improve cessation outcome (ABST_EOT) relative to placebo?

Study Description

The goal of this genetically informed randomized smoking cessation trial is to identify the most appropriate smoking cessation treatments for smokers based on genetic information. We will recruit 720 participants from a previous study who agreed to be contacted again to participate in a smoking cessation trial. These participants also previously provided a DNA sample for genetic analysis as part of that study. Participants who are actively nicotine dependent will be randomly assigned to receive combination Nicotine Replacement Therapy (i.e., the nicotine patch and nicotine lozenge), varenicline, or placebo (patch/lozenge, or pill) for 3 months. All participants will receive intensive smoking cessation counseling for 3 months. They will be followed over the course of one year. We will study the effect of the nicotine replacement therapy (nicotine patch and lozenge) and varenicline on smoking outcomes and whether the effect differs according to the genetic makeup of the participants.

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