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: July 15, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Nicotine Addiction
Drug: Varenicline
Drug: Placebo
Drug: Transdermal Nicotine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Enrollment: 1246
Study Start Date: December 2010
Estimated Study Completion Date: September 2014
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo Pill (12 weeks) & Placebo Patch (11 weeks) + smoking cessation counseling
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: 7mg placebo patch

Other Names:
  • Placebo pills
  • Placebo patches
Active Comparator: Varenicline
Varenicline (12 weeks) & Placebo Patch (11 weeks) + smoking cessation counseling
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
Active Comparator: Transdermal Nicotine
Placebo Pill (12 weeks) & Transdermal Patch (11 weeks) + smoking cessation counseling
Drug: Transdermal Nicotine
Week 1-6: 21mg nicotine patch Week 7-8: 14mg nicotine patch Week 9-11: 7mg nicotine patch
Other Names:
  • Nicoderm CQ
  • Nicotine Patch

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01314001

Locations
United States, New York
University at Buffalo - State University of New York
Buffalo, New York, United States, 14260
United States, Pennsylvania
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
MD Anderson Cancer Center, University of Texas
Houston, Texas, United States, 77230
Canada, Ontario
Centre for Addiction and Mental Health, University of Toronto
Toronto, Ontario, Canada, M5T1RH
Sponsors and Collaborators
University of Pennsylvania
Investigators
Principal Investigator: Caryn Lerman, PhD University of Pennsylvania
Principal Investigator: Rachel F Tyndale, PhD University of Toronto
  More Information

No publications provided

Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01314001     History of Changes
Other Study ID Numbers: 811722, U01DA020830
Study First Received: March 10, 2011
Last Updated: July 15, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by University of Pennsylvania:
Tobacco, Smoking, Varenicline, Nicotine Patch

Additional relevant MeSH terms:
Tobacco Use Disorder
Behavior, Addictive
Substance-Related Disorders
Mental Disorders
Compulsive Behavior
Impulsive Behavior
Nicotine
Nicotine polacrilex
Varenicline
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Central Nervous System Stimulants
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 29, 2014