Metabolism-informed Care for Smoking Cessation

NCT03227679 | Completed

• 1 other identifier: 160512
• Study Type: interventional
• Target: 82
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Tobacco Use; Tobacco Use Cessation

Keywords

Personalized Medicine; Nicotine Metabolite Ratio (NMR); Varenicline; Nicotine Replacement Therapy (NRT); Smoking Cessation; Pharmacotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Confidence in Quitting

  Baseline - 6 months

• Medication Use/Compliance

  1 - 6 months

• Smoking Status

  6 months

Study Arms (2)

Metabolism-Informed Care (MIC)

ACTIVE COMPARATOR

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; Drug: Varenicline; Drug: Bupropion; Drug: Nicotine patch

Guideline-Based Care (GBC)

ACTIVE COMPARATOR

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; Drug: Bupropion; Drug: Nicotine patch

Interventions

Nicotine Metabolite Ratio OTHER

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.

Metabolism-Informed Care (MIC)

Varenicline DRUG

FDA-approved smoking cessation pharmacotherapy

Also known as: Chantix

Guideline-Based Care (GBC); Metabolism-Informed Care (MIC)

Bupropion DRUG

FDA-approved smoking cessation pharmacotherapy

Also known as: Zyban

Guideline-Based Care (GBC); Metabolism-Informed Care (MIC)

Nicotine patch DRUG

FDA-approved smoking cessation pharmacotherapy

Also known as: Nicotine Replacement Therapy (NRT)

Guideline-Based Care (GBC); Metabolism-Informed Care (MIC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Related Publications (12)

• World Health Organization. Assessment of the Economic Costs of Smoking. Economics of tobacco toolkit. 2011;:1-116.

  BACKGROUND

• Agaku IT, King BA, Dube SR; Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults - United States, 2005-2012. MMWR Morb Mortal Wkly Rep. 2014 Jan 17;63(2):29-34.

  PMID: 24430098 BACKGROUND

• Benowitz NL. Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol. 2009;49:57-71. doi: 10.1146/annurev.pharmtox.48.113006.094742.

  PMID: 18834313 BACKGROUND

• Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005 Mar;57(1):79-115. doi: 10.1124/pr.57.1.3.

  PMID: 15734728 BACKGROUND

• Chen LS, Bloom AJ, Baker TB, Smith SS, Piper ME, Martinez M, Saccone N, Hatsukami D, Goate A, Bierut L. Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6). Addiction. 2014 Jan;109(1):128-137. doi: 10.1111/add.12353. Epub 2013 Nov 11.

  PMID: 24033696 BACKGROUND

• Dempsey D, Tutka P, Jacob P 3rd, Allen F, Schoedel K, Tyndale RF, Benowitz NL. Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther. 2004 Jul;76(1):64-72. doi: 10.1016/j.clpt.2004.02.011.

  PMID: 15229465 BACKGROUND

• Lerman C, Schnoll RA, Hawk LW Jr, Cinciripini P, George TP, Wileyto EP, Swan GE, Benowitz NL, Heitjan DF, Tyndale RF; PGRN-PNAT Research Group. Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo-controlled trial. Lancet Respir Med. 2015 Feb;3(2):131-138. doi: 10.1016/S2213-2600(14)70294-2. Epub 2015 Jan 12.

  PMID: 25588294 BACKGROUND

• Hughes JR, Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014 Jan 8;2014(1):CD000031. doi: 10.1002/14651858.CD000031.pub4.

  PMID: 24402784 BACKGROUND

• Bauld L, Bell K, McCullough L, Richardson L, Greaves L. The effectiveness of NHS smoking cessation services: a systematic review. J Public Health (Oxf). 2010 Mar;32(1):71-82. doi: 10.1093/pubmed/fdp074. Epub 2009 Jul 28.

  PMID: 19638397 BACKGROUND

• 2008 PHS Guideline Update Panel, Liaisons, and Staff. Treating tobacco use and dependence: 2008 update U.S. Public Health Service Clinical Practice Guideline executive summary. Respir Care. 2008 Sep;53(9):1217-22. No abstract available.

  PMID: 18807274 BACKGROUND

• Bush K, Kivlahan DR, McDonell MB, Fihn SD, Bradley KA. The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking. Ambulatory Care Quality Improvement Project (ACQUIP). Alcohol Use Disorders Identification Test. Arch Intern Med. 1998 Sep 14;158(16):1789-95. doi: 10.1001/archinte.158.16.1789.

  PMID: 9738608 BACKGROUND

• Anthenelli RM, Benowitz NL, West R, St Aubin L, McRae T, Lawrence D, Ascher J, Russ C, Krishen A, Evins AE. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016 Jun 18;387(10037):2507-20. doi: 10.1016/S0140-6736(16)30272-0. Epub 2016 Apr 22.

  PMID: 27116918 BACKGROUND

MeSH Terms

Conditions

Tobacco Use; Tobacco Use Cessation; Smoking Cessation

Interventions

Varenicline; Bupropion; Tobacco Use Cessation Devices; Nicotine Replacement Therapy

Condition Hierarchy (Ancestors)

Behavior; Health Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Propiophenones; Ketones; Organic Chemicals; Therapeutics; Drug Therapy

Study Officials

• Quinn Wells, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Dawn Beaulieu, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Matthew Freiberg, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Hilary Tindle, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participant, Nurse, and RAs all blinded to random Arm assignment, none blinded to medication prescription
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Parallel arm pilot trial with a single-arm crossover design

Study Record Dates

• First Submitted: June 29, 2017
• First Posted: July 24, 2017
• Study Start: May 18, 2016
• Primary Completion: October 8, 2016
• Study Completion: April 18, 2017
• Last Updated: January 6, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share