Pharmacogenetics of Nicotine Addiction Treatment

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01314001
First received: March 10, 2011
Last updated: April 15, 2014
Last verified: April 2014

March 10, 2011
April 15, 2014
January 2011
September 2013   (final data collection date for primary outcome measure)
7-day point prevalence quit rate [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
The definition of this measure requires: (a) no self-reported smoking (not even a puff of a cigarette) for at least the 7 days prior to the assessment, and (b) biochemical verification of abstinence.
7-day point prevalence quit rate [ Time Frame: 7 days ] [ Designated as safety issue: No ]
The definition of this measure requires: (a) no self-reported smoking (not even a puff of a cigarette) for at least the 7 days prior to the assessment, and (b) biochemical verification of abstinence.
Complete list of historical versions of study NCT01314001 on ClinicalTrials.gov Archive Site
  • Continuous Abstinence (11 weeks) [ Time Frame: Weeks -1, 0, 1, 4, 8, 11, & 24 ] [ Designated as safety issue: No ]
    The definition of this measure requires: Not taking even 1 cigarette puff from target quit date to end of treatment.
  • Cost-effectiveness Ratio [ Time Frame: Weeks -1, 0, 1, 4, 8, 11, & 24 ] [ Designated as safety issue: No ]
    Incremental cost-effectiveness ratio (ICER) will be calculated as a ratio of the difference between mean costs in each treatment group and the difference between the cessation rates across the treatment arms at weeks 11 and 24.
  • Time to Relapse [ Time Frame: Weeks -1, 0, 1, 4, 8, 11, & 24 ] [ Designated as safety issue: No ]
    The definition of this measure is the number of consecutive days of abstinence following target quit date.
  • 7-day point prevalence quit rate [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The definition of this measure requires: (a) no self-reported smoking (not even a puff of a cigarette) for at least the 7 days prior to the assessment, and (b) biochemical verification of abstinence.
  • Continuous Abstinence (11 weeks) [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]
    The definition of this measure requires: Not taking even 1 cigarette puff from target quit date to end of treatment.
  • Cost-effectiveness Ratio [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Incremental cost-effectiveness ratio (ICER) will be calculated as a ratio of the difference between mean costs in each treatment group and the difference between the cessation rates across the treatment arms at weeks 11, 24 and 52.
  • Time to Relapse [ Time Frame: 11 weeks ] [ Designated as safety issue: No ]
    The definition of this measure is the number of consecutive days of abstinence following target quit date.
Not Provided
Not Provided
 
Pharmacogenetics of Nicotine Addiction Treatment
Pharmacogenetics of Nicotine Addiction Treatment (PNAT)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Nicotine Addiction
  • Drug: Varenicline
    Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally
    Other Name: Chantix
  • Drug: Placebo

    Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally

    Week 1 - 6: 21mg placebo patch Week 7 - 8: 14mg placebo patch Week 9 - 11: 7 mg placebo patch

    Other Names:
    • Placebo pills
    • Placebo patches
  • Drug: Transdermal Nicotine
    Week 1-6: 21 mg nicotine patch Week 7-8: 14 mg nicotine patch Week 9-11: 7 mg nicotine patch
    Other Names:
    • Nicoderm CQ
    • Nicotine Patch
  • Placebo Comparator: Placebo
    Placebo Pill (12 weeks) & Placebo Patch (11 weeks) + smoking cessation counseling
    Intervention: Drug: Placebo
  • Active Comparator: Varenicline
    Varenicline (12 weeks) & Placebo Patch (11 weeks) + smoking cessation counseling
    Intervention: Drug: Varenicline
  • Active Comparator: Transdermal Nicotine
    Placebo Pill (12 weeks) & Transdermal Patch (11 weeks) + smoking cessation counseling
    Intervention: Drug: Transdermal Nicotine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1246
September 2014
September 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

Eligible participants will be males and females

  1. Between the ages of 18-65.
  2. Smoke at least 10 cigarettes/day for the past 6 months.
  3. Provide a baseline Carbon Monoxide (CO) reading greater than 10ppm at the Intake Session.
  4. Are seeking smoking cessation treatment.
  5. Plan to live in the area for the next 12 months.
  6. Fluent English speaker.
  7. 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

  1. Regular (daily) use of chewing tobacco, snuff or snus.
  2. Current enrollment or plans to enroll in another smoking cessation or research program in the next 12 months.
  3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 12 months.
  4. Provide a baseline CO reading less than or equal to 10ppm at the Intake Session.

Alcohol/Drug Exclusion Criteria

  1. History (within the last year) or currently receiving treatment for substance abuse (e.g., alcohol, opioids, cocaine, marijuana, or stimulants), excluding nicotine.
  2. Current use of cocaine and/or methamphetamines (urine drug screen at the Intake Session).
  3. Current alcohol consumption that exceeds greater than 25 standard drinks/week.
  4. Current alcohol abuse or dependence.
  5. Current non-alcoholic psychoactive substance abuse or dependence.

Medical Exclusion Criteria

  1. Women who are pregnant, planning a pregnancy, or lactating.
  2. History of epilepsy or a seizure disorder.
  3. Current medical problems for which transdermal nicotine is contraindicated including:

    • Allergy to latex.
    • History of kidney and/or liver disease, including transplant (self-report).
    • Uncontrolled hypertension (determined as a Systolic Blood pressure (SBP) reading greater than 160 and/or a Diastolic Blood Pressure (DBP) greater than 100).
  4. Serious or unstable disease within the past 6 months.
  5. History (last 6 months) of abnormal heart rhythms, tachycardia and cardiovascular disease (stroke, angina, heart attack) may result in ineligibility. These conditions will be evaluated on a case by case basis by the Study Physician.
  6. Inability to provide a blood sample to be used to assess nicotine metabolite ratio.

Psychiatric Exclusion Criteria (as determined by self report & MINI)

  1. Current diagnosis of major depression. Persons with a history of major depression, if stable for 6 months or longer, are eligible, provided they are not excluded based on medications (below).
  2. Any suicide risk score on MINI or self-reported suicide attempt on telephone screen.
  3. Current or past hypomanic/manic episode.
  4. History or current diagnosis of Post Traumatic Stress Disorder (PTSD).
  5. History or current diagnosis of psychotic disorder, bipolar disorder, schizophrenia.

Medication Exclusion Criteria

  1. Current use or recent discontinuation (within the last 14-days) of:

    • Smoking cessation medication (e.g. Zyban, Wellbutrin, Wellbutrin SR, Chantix); NOTE: Once participants are found eligible for the study, they are instructed to use the smoking cessation medication provided to them by the study staff. If a subject reports an isolated (non-daily) instance of using a non-study smoking cessation medication, the study physician and PI will evaluate the situation and determine if it is safe for the subject to continue participation.
    • Anti-psychotic medications.
    • Certain medications used to treat depression, including Wellbutrin, Monoamine Oxidase Inhibitors (MAOIs), and tricyclic antidepressants.
    • Prescription stimulants (e.g. Provigil, Ritalin, Adderall).
  2. Current use of:

    • Nicotine replacement therapy (NRT); NOTE: Once participants are found eligible for the study, they are told they should only use the NRT provided to them by the study staff. If a subject reports an isolated (non-daily) instance of NRT use during the study, they may be permitted to continue.
    • Tagamet (cimetidine).
    • Heart medications such as digoxin, quinidine, nitroglycerin; use of these medications may result in ineligibility and will therefore be evaluated on a case-by-case basis by the Study Physician.
    • Anti-coagulants (e.g., Coumadin, Warfarin).
  3. Daily use of:

    • Opiate-containing medications for chronic pain; if a participant reports taking an opiate-containing medication every day for the 14 days prior to the telephone screen and/or Intake Session, the participant will be ineligible.
    • Rescue Inhalers (e.g. albuterol, proventil, ventolin, or maxair)

General Exclusion

  1. Any medical condition, illness, disorder or concomitant medication that could compromise participant safety or treatment, as determined by the Principal Investigator and/or Study Physician.
  2. Inability to provide informed consent or complete any of the study tasks as determined by the Principal Investigator and/or Study Physician.
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT01314001
811722, U01DA020830
Yes
University of Pennsylvania
University of Pennsylvania
National Institute on Drug Abuse (NIDA)
Principal Investigator: Caryn Lerman, PhD University of Pennsylvania
Principal Investigator: Rachel F Tyndale, PhD University of Toronto
University of Pennsylvania
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP