Pharmacogenetics of Nicotine Addiction Treatment (PNAT)
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Nicotine Addiction
- Sponsor
- University of Pennsylvania
- Enrollment
- 1246
- Locations
- 4
- Primary Endpoint
- 7-day Point Prevalence Quit Rate at End-of-Treatment (EOT)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
The purpose of this research program is to understand how a biomarker called the "nicotine metabolite ratio" (also referred to as NMR) may influence a smoker's ability to quit smoking.
Detailed Description
Smoking is an enormous public health problem with a great need for research to improve treatment outcomes. Our prior data indicates that the cytochrome P450 2A6 (CYP2A6) enzyme is critical in the metabolic inactivation of nicotine, and also influences smoking behavior and response to therapies. With a vision toward translation of our research to practice, we have characterized a genetically-informed biomarker of CYP2A6 activity, specifically the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine), which reflects both CYP2A6 genetic variation and environmental influences on CYP2A6 activity. The NMR is measured non-invasively in smokers with established reliability, stability, analytic validity, and efficacy as a predictor of the ability to quit smoking and treatment response in multiple retrospective trials. Translation of these findings to clinical practice requires validation in a prospective clinical trial comparing alternative therapies for smoking cessation. Thus, the proposed trial is a prospective, stratified, placebo-controlled, multi-center clinical trial of alternative therapies for smoking cessation treatment in approximately 1,200 smokers. Randomization to placebo (PLA), transdermal nicotine (TN), or varenicline (VAR) will be stratified prospectively based on the nicotine metabolite ratio (NMR). Abstinence from smoking at the end of treatment will be the primary outcome. Quit rate at 6-month follow-up is a secondary outcome. To facilitate translation to practice, analysis of the cost-effectiveness of our proposed approach will also be completed. The proposed research provides the next critical step to validate a genetically-informed diagnostic tool, the NMR, which clinicians can use in the future to optimize treatment decisions for their patients who wish to quit smoking.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eligible participants will be males and females
- •Between the ages of 18-
- •Smoke at least 10 cigarettes/day for the past 6 months.
- •Provide a baseline Carbon Monoxide (CO) reading greater than 10ppm at the Intake Session.
- •Are seeking smoking cessation treatment.
- •Plan to live in the area for the next 12 months.
- •Fluent English speaker.
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the combined consent and Health Insurance Portability and Accountability Act (HIPAA) form. All subjects must consent to use a medically accepted method of birth control (e.g., condoms and spermicide, oral contraceptive, Depo-Provera injection, contraceptive patch, tubal ligation) or abstain from sexual intercourse during the time they are taking study medication (pills and patches) and for at least one month after the medication period ends. All female subjects of child-bearing potential should not be pregnant for the duration of the study.
Exclusion Criteria
- •Smoking Behavior
- •Regular (daily) use of chewing tobacco, snuff or snus.
- •Current enrollment or plans to enroll in another smoking cessation or research program in the next 12 months.
- •Plan to use other nicotine substitutes or smoking cessation treatments in the next 12 months.
- •Provide a baseline CO reading less than or equal to 10ppm at the Intake Session.
- •Alcohol/Drug Exclusion Criteria
- •History (within the last year) or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants), excluding nicotine.
- •Current use of cocaine and/or methamphetamines (urine drug screen at the Intake Session).
- •Current alcohol consumption that exceeds greater than 25 standard drinks/week.
- •Current alcohol abuse or dependence.
Arms & Interventions
Placebo (Slow Metabolizers)
Subjects in this arm are those identified as slow metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks \& wear a placebo patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions.
Intervention: Placebo
Varenicline (Slow Metabolizers)
Subjects in this arm are those identified as slow metabolizers of nicotine (based on their NMR) and will take active varenicline pills daily for twelve weeks \& wear a placebo patch daily for eleven weeks. When taking the active varenicline, subjects will follow the same treatment regimen per the manufacturer. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions.
Intervention: Varenicline
Transdermal Nicotine (Slow Metabolizers)
Subjects in this arm are those identified as slow metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks \& will wear an active transdermal nicotine patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. When wearing the active transdermal nicotine, subjects will follow the same treatment regimen per the manufacturer. All subjects in this arm will receive smoking cessation counseling during their sessions.
Intervention: Transdermal Nicotine
Placebo (Normal Metabolizers)
Subjects in this arm are those identified as normal metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks \& wear a placebo patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions.
Intervention: Placebo
Varenicline (Normal Metabolizers)
Subjects in this arm are those identified as normal metabolizers of nicotine (based on their NMR) and will take active varenicline pills daily for twelve weeks \& wear a placebo patch daily for eleven weeks. When taking the active varenicline, subjects will follow the same treatment regimen per the manufacturer. The placebo patch will look identical to the active transdermal nicotine patches; however, they do not contain actual nicotine. Subjects will follow the same regimen as those in the active transdermal nicotine arm. All subjects in this arm will receive smoking cessation counseling during their sessions.
Intervention: Varenicline
Transdermal Nicotine (Normal Metabolizers)
Subjects in this arm are those identified as normal metabolizers of nicotine (based on their NMR) and will take placebo pills daily for twelve weeks \& will wear an active transdermal nicotine patch daily for eleven weeks. The placebo pill will look identical to the active varenicline tablets; however, they will not contain any active medication. Subjects will follow the same drug regimen as those in the active varenicline arm. When wearing the active transdermal nicotine, subjects will follow the same treatment regimen per the manufacturer. All subjects in this arm will receive smoking cessation counseling during their sessions.
Intervention: Transdermal Nicotine
Outcomes
Primary Outcomes
7-day Point Prevalence Quit Rate at End-of-Treatment (EOT)
Time Frame: Week 11
The percentage of ITT subjects who were verified as abstinent. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers.
Secondary Outcomes
- 7-day Point Prevalence Quit Rate at 6-month Follow up Survey(Week 24)
- Total Side-Effect Severity Index at Pre-Quit(Pre-Quit (Week -1/Baseline))
- Total Side-Effect Severity Index at Target Quit Date(Target Quit Date (Week 0))
- Total Side-Effect Severity Index at Week 1(Week 1)
- Total Side-Effect Severity Index at Week 4(Week 4)