Metabolism-informed Care for Smoking Cessation

Study Overview
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Brief Summary
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Nicotine mediates smoking's addictive effects in the brain. The ratio of 3-hydroxycotinine to cotinine, known as the nicotine metabolite ratio, or NMR, is a genetically- informed biomarker reflecting hepatic CYP2A6 activity and the rate of nicotine metabolism. In light of a recent randomized controlled trial (RCT) in humans in Lancet Respiratory Medicine, which found that the NMR can be used to individualize treatment for smokers, our pilot study aims to determine the feasibility of using NMR to guide selection of pharmacotherapy in clinical populations of daily smokers.

Detailed Description
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Consenting participants will be assigned to guideline-based care (GBC: incorporating national guidelines and more recent evidence from clinical trials of pharmacotherapy for smoking cessation) or metabolism-informed care (MIC: identical to GBC but selection of medication based on NMR result). All participants received counseling from a nurse level certified tobacco counseling. After consent, participants undergo a blood draw for NMR, complete a baseline questionnaire, and are randomized to GBC or MIC. At approximately 1, 3, and 6 months post-consent, participants will provide follow up information via telephone questionnaire regarding symptoms, confidence in quitting, use of medications, and smoking status. At the 6-month follow-up time point, if a participant self-reports abstinence from smoking, the participant will be asked to complete a survey in-person and provide a sample of end-expired carbon monoxide for biochemical validation. At the 6 month time point, GBC participants who continue to smoke will be offered an additional phone call from the nurse tobacco counselor in which the results of the baseline NMR test will be given, along with a second prescription for a smoking cessation medication based on the NMR results (i.e., single arm crossover design). Two weeks after this additional phone call, the patient will be contacted for a final survey regarding use of medication and smoking status.

Official Title
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Metabolism-informed Care for Smoking Cessation

Conditions
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Tobacco Use Cessation, Tobacco Use

Intervention / Treatment
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* Other: Nicotine Metabolite Ratio
* Drug: Varenicline
* Drug: Bupropion
* Drug: Nicotine patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Smokes ≥ 5 cigarettes per day Willing to give up all forms of tobacco (5/10/2016 - 6/27/2016) Medically cleared (i.e., no contraindications in Section 3) to receive at least 2 FDA- approved smoking cessation medications Willing to use the medications for which medically cleared (individually, not in combination; only applicable if Medically Cleared = Yes) Exclusion Criteria: Current diagnosis of schizophrenia, psychosis, active suicidal ideation, dementia, or severe mental retardation Receiving palliative or hospice care Currently pregnant or breastfeeding Hospitalized for a psychiatric condition in the past year (5/10/2016 - 6/27/2016) Hospitalized for a psychiatric condition in the past 3 months or change in psychiatric medications in last 3 months (6/28/2016 forward) Telephone problems that would preclude participation (e.g., can't receive calls reliably) Not able to read and speak English Abstinent from cigarettes for >3 days (b/c NMR not reliable after 72 hours) Used smoking cessation medications in the last 7 days (5/10/2016 - 6/27/2016)

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Parallel arm pilot trial with a single-arm crossover design
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metabolism-Informed Care (MIC)<br>Smoking Cessation Pharmacotherapy (varenicline, bupropion, and nicotine patch) recommendations were guided by Nicotine Metabolism as measured by the Nicotine Metabolite Ratio. Ultimately, after being educated about smoking cessation medication efficacy and side-effects, the participant could decide to take any medication for which they were medically cleared, but the recommendation was made based on rate of Nicotine Metabolism. | Other: Nicotine Metabolite Ratio<br>* This intervention used information from a genetically-informed biomarker (Nicotine Metabolite Ratio, NMR) to assign one of 3 FDA-approved smoking cessation pharmacotherapies (varenicline, bupropion, or NRT) to participants.<br>Drug: Varenicline<br>* FDA-approved smoking cessation pharmacotherapy<br>* Other names: Chantix;Drug: Bupropion<br>* FDA-approved smoking cessation pharmacotherapy<br>* Other names: Zyban;Drug: Nicotine patch<br>* FDA-approved smoking cessation pharmacotherapy<br>* Other names: Nicotine Replacement Therapy (NRT);|
| Active Comparator: Guideline-Based Care (GBC)<br>Smoking Cessation Pharmacotherapy (varenicline, bupropion, and nicotine patch) was co-selected from those they were medically able to receive after educating participants about smoking cessation medication efficacy and side-effects. | Drug: Varenicline<br>* FDA-approved smoking cessation pharmacotherapy<br>* Other names: Chantix;Drug: Bupropion<br>* FDA-approved smoking cessation pharmacotherapy<br>* Other names: Zyban;Drug: Nicotine patch<br>* FDA-approved smoking cessation pharmacotherapy<br>* Other names: Nicotine Replacement Therapy (NRT);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Theoretical Endorsement of MIC as assessed by level of agreement to a set of seven 5-point Likert Scale questions | Likert Scale from Strongly Disagree to Strongly Agree on items assessing attitudes toward and perceptions of using metabolism information to guide medical care | Baseline | 
| Acceptance of MIC medication recommendation as assessed by concordance between MIC recommendation and actual prescribed medication | Level of agreement between participant's prescribed medication and the medication that would be recommended based on Nicotine Metabolite Ratio | At 4 weeks post-baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confidence in Quitting | Self-reported confidence in ability to quit | Baseline - 6 months | 
| Medication Use/Compliance | Use of prescribed medication, as directed | 1 - 6 months | 
| Smoking Status | Self-reported and/or biochemically validated smoking cessation | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Varenicline, Personalized Medicine, Nicotine Metabolite Ratio (NMR), Nicotine Replacement Therapy (NRT), Smoking Cessation, Pharmacotherapy