- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03227679
Metabolism-informed Care for Smoking Cessation
July 20, 2017 updated by: Hilary Tindle, Vanderbilt University Medical Center
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
82
Phase
- Not Applicable
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Health Services Research
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Metabolism-Informed Care (MIC)
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.
|
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.
FDA-approved smoking cessation pharmacotherapy
Other Names:
FDA-approved smoking cessation pharmacotherapy
Other Names:
FDA-approved smoking cessation pharmacotherapy
Other Names:
|
Active Comparator: Guideline-Based Care (GBC)
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.
|
FDA-approved smoking cessation pharmacotherapy
Other Names:
FDA-approved smoking cessation pharmacotherapy
Other Names:
FDA-approved smoking cessation pharmacotherapy
Other Names:
|
What is the study measuring?
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
Time Frame: Baseline
|
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
Time Frame: At 4 weeks post-baseline
|
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
Time Frame: Baseline - 6 months
|
Self-reported confidence in ability to quit
|
Baseline - 6 months
|
Medication Use/Compliance
Time Frame: 1 - 6 months
|
Use of prescribed medication, as directed
|
1 - 6 months
|
Smoking Status
Time Frame: 6 months
|
Self-reported and/or biochemically validated smoking cessation
|
6 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: 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
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- World Health Organization. Assessment of the Economic Costs of Smoking. Economics of tobacco toolkit. 2011;:1-116.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 18, 2016
Primary Completion (Actual)
October 8, 2016
Study Completion (Actual)
April 18, 2017
Study Registration Dates
First Submitted
June 29, 2017
First Submitted That Met QC Criteria
July 20, 2017
First Posted (Actual)
July 24, 2017
Study Record Updates
Last Update Posted (Actual)
July 24, 2017
Last Update Submitted That Met QC Criteria
July 20, 2017
Last Verified
July 1, 2017
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Agents
- Enzyme Inhibitors
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Cytochrome P-450 Enzyme Inhibitors
- Ganglionic Stimulants
- Nicotinic Agonists
- Cholinergic Agonists
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Dopamine Uptake Inhibitors
- Nicotine
- Bupropion
- Varenicline
Other Study ID Numbers
- 160512
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
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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