Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
1246 participants
INTERVENTIONAL
2010-12-31
2014-09-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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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.
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
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.
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
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.
Transdermal Nicotine
Week 1-6: 21mg nicotine patch Week 7-8: 14mg nicotine patch Week 9-11: 7mg nicotine patch
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.
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
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.
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
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.
Transdermal Nicotine
Week 1-6: 21mg nicotine patch Week 7-8: 14mg nicotine patch Week 9-11: 7mg nicotine patch
Interventions
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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
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
Transdermal Nicotine
Week 1-6: 21mg nicotine patch Week 7-8: 14mg nicotine patch Week 9-11: 7mg nicotine patch
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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.
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.
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.
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.
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.
18 Years
65 Years
ALL
No
Sponsors
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National Institute on Drug Abuse (NIDA)
NIH
University of Pennsylvania
OTHER
Responsible Party
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Principal Investigators
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Caryn Lerman, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Pennsylvania
Rachel F Tyndale, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Toronto
Locations
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University at Buffalo - State University of New York
Buffalo, New York, United States
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania
Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center, University of Texas
Houston, Texas, United States
Centre for Addiction and Mental Health, University of Toronto
Toronto, Ontario, Canada
Countries
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References
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Tonkin SS, Betts JM, Dowd AN, Mahoney MC, Cinciripini PM, Schnoll RA, George TP, Tyndale RF, Hawk LW Jr. Daily cigarette abstinence and smoking rate with varenicline: Relationships with treatment, craving, and affect during the first week of the quit attempt. Nicotine Tob Res. 2025 May 4:ntaf095. doi: 10.1093/ntr/ntaf095. Online ahead of print.
Chenoweth MJ, Kim YJ, Nollen NL, Hawk LW Jr, Mahoney MC, Lerman C, Knight J, Tyndale RF. Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline. Clin Pharmacol Ther. 2024 Jun;115(6):1277-1281. doi: 10.1002/cpt.3210. Epub 2024 Feb 19.
Chenoweth MJ, Lerman C, Knight J, Tyndale RF. Influence of CYP2A6 Genetic Variation, Nicotine Dependence Severity, and Treatment on Smoking Cessation Success. Nicotine Tob Res. 2023 May 22;25(6):1207-1211. doi: 10.1093/ntr/ntac268.
Tonkin SS, Colder C, Mahoney MC, Swan GE, Cinciripini P, Schnoll R, George TP, Tyndale RF, Hawk LW. Evaluating Treatment Mechanisms of Varenicline: Mediation by Affect and Craving. Nicotine Tob Res. 2022 Oct 26;24(11):1803-1810. doi: 10.1093/ntr/ntac138.
Chenoweth MJ, Lerman C, Knight J, Tyndale RF. A Genome-Wide Association Study of Nausea Incidence in Varenicline-Treated Cigarette Smokers. Nicotine Tob Res. 2021 Aug 29;23(10):1805-1809. doi: 10.1093/ntr/ntab044.
El-Boraie A, Chenoweth MJ, Pouget JG, Benowitz NL, Fukunaga K, Mushiroda T, Kubo M, Nollen NL, Sanderson Cox L, Lerman C, Knight J, Tyndale RF. Transferability of Ancestry-Specific and Cross-Ancestry CYP2A6 Activity Genetic Risk Scores in African and European Populations. Clin Pharmacol Ther. 2021 Oct;110(4):975-985. doi: 10.1002/cpt.2135. Epub 2021 Jan 1.
Peng AR, Swardfager W, Benowitz NL, Ahluwalia JS, Lerman C, Nollen NL, Tyndale RF. Impact of early nausea on varenicline adherence and smoking cessation. Addiction. 2020 Jan;115(1):134-144. doi: 10.1111/add.14810. Epub 2019 Nov 5.
Ashare RL, Thompson M, Leone F, Metzger D, Gross R, Mounzer K, Tyndale RF, Lerman C, Mahoney MC, Cinciripini P, George TP, Collman RG, Schnoll R. Differences in the rate of nicotine metabolism among smokers with and without HIV. AIDS. 2019 May 1;33(6):1083-1088. doi: 10.1097/QAD.0000000000002127.
Robinson JD, Li L, Chen M, Lerman C, Tyndale RF, Schnoll RA, Hawk LW, George TP, Benowitz NL, Cinciripini PM. Evaluating the temporal relationships between withdrawal symptoms and smoking relapse. Psychol Addict Behav. 2019 Mar;33(2):105-116. doi: 10.1037/adb0000434. Epub 2019 Jan 7.
Peng AR, Schnoll R, Hawk LW Jr, Cinciripini P, George TP, Lerman C, Tyndale RF. Predicting smoking abstinence with biological and self-report measures of adherence to varenicline: Impact on pharmacogenetic trial outcomes. Drug Alcohol Depend. 2018 Sep 1;190:72-81. doi: 10.1016/j.drugalcdep.2018.04.035. Epub 2018 Jun 26.
Hamilton DA, Mahoney MC, Novalen M, Chenoweth MJ, Heitjan DF, Lerman C, Tyndale RF, Hawk LW Jr. Test-Retest Reliability and Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking Smokers. Nicotine Tob Res. 2015 Dec;17(12):1505-9. doi: 10.1093/ntr/ntv031. Epub 2015 Mar 1.
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.
Chenoweth MJ, Novalen M, Hawk LW Jr, Schnoll RA, George TP, Cinciripini PM, Lerman C, Tyndale RF. Known and novel sources of variability in the nicotine metabolite ratio in a large sample of treatment-seeking smokers. Cancer Epidemiol Biomarkers Prev. 2014 Sep;23(9):1773-82. doi: 10.1158/1055-9965.EPI-14-0427. Epub 2014 Jul 10.
Other Identifiers
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811722
Identifier Type: -
Identifier Source: org_study_id
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