Metabolism-informed Care for Smoking Cessation

Tobacco Use Clinical Trial

Official title:

Metabolism-informed Care for Smoking Cessation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03227679
• Other study ID #: 160512
• Status: Completed
• Phase: N/A
• First received: June 29, 2017
• Last updated: July 20, 2017
• Start date: May 18, 2016
• Est. completion date: April 18, 2017

Study information

• Verified date: July 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: April 18, 2017
• Est. primary completion date: October 8, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Tobacco Use
• Tobacco Use Cessation

Intervention

Other:
• Nicotine Metabolite Ratio
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.

Drug:
• Varenicline
FDA-approved smoking cessation pharmacotherapy
• Bupropion
FDA-approved smoking cessation pharmacotherapy
• Nicotine patch
FDA-approved smoking cessation pharmacotherapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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):128-37. doi: 10.1111/add.12353. Epub 2013 Nov 11. — View Citation

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. — View Citation

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

Hukkanen J, Jacob P 3rd, Benowitz NL. Metabolism and disposition kinetics of nicotine. Pharmacol Rev. 2005 Mar;57(1):79-115. Review. — View Citation

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. — View Citation

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

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Confidence in Quitting	Self-reported confidence in ability to quit	Baseline - 6 months
Secondary	Medication Use/Compliance	Use of prescribed medication, as directed	1 - 6 months
Secondary	Smoking Status	Self-reported and/or biochemically validated smoking cessation	6 months