Evaluation of a Tailored Smoking Cessation Treatment Algorithm Based on Initial Treatment Response and Genotype

NCT ID: NCT00894166

Last Updated: 2013-09-23

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

606 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2011-10-31

Brief Summary

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Nicotine replacement therapy (NRT) is a well-tolerated and efficacious smoking cessation treatment, and yet many smokers fail to quit using NRT. Many of these smokers may benefit from prescription treatment alternatives, including Zyban or Chantix. In this study, the investigators propose to develop and evaluate a stepped-care treatment algorithm that would evaluate whether smokers who receive treatment with NRT should be supplemented with Zyban or switched to Chantix only based on: 1) their initial response to NRT; and 2) individual genetic factors found to predict smoking cessation in other studies evaluating these treatments. This study is a continuation of our previous studies showing that abstinence rates can be increased by starting nicotine patch therapy two weeks before the quit date. The investigators will provide pre-cessation NRT to all participants initially. Those who do not show a favorable response on early indicators of success (e.g., smoking in the first week after the target quit-smoking date) will receive "rescue" treatment by having their NRT treatment supplemented with Zyban , by being switched to treatment with Chantix or will remain on NRT (control).

The investigators hypothesize that "Rescue" treatment with Zyban in combination with NRT or Chantix will increase success rates over leaving subjects on NRT when they are NRT insufficient responders, i.e. they have shown an unfavorable response to NRT in the first week pre-quit or the first week post-quit.

Detailed Description

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Conditions

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Smoking Cessation

Keywords

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Smoking Cessation Chantix varenicline Nicotine Replacement Therapy Nicotine Patches Zyban bupropion Quit Smoking

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Nicotine Replacement Therapy Responder

Nicotine Responders

Group Type ACTIVE_COMPARATOR

Nicotine Patches

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Pre-Quit Rescue to Bupropion & Nicotine

Participants not responsive to nicotine patches who are randomly assigned at week 2 to use of Zyban (bupropion) in combination with nicotine patches

Group Type ACTIVE_COMPARATOR

Nicotine patches, then bupropion & nicotine patches (Pre-Quit)

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.

Pre-Quit Rescue to Varenicline

Participants not responsive to nicotine patches who are randomly assigned at week 2 to use of Chantix (varenicline)

Group Type ACTIVE_COMPARATOR

Nicotine patches, then varenicline (Pre-Quit)

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks)

Pre-Quit Rescue to Nicotine

Participants not responsive to nicotine patches who are randomly assigned at week 2 to continued use of nicotine patches

Group Type ACTIVE_COMPARATOR

Nicotine patches, then nicotine patches (Pre-Quit)

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Post-Quit Rescue to Bupropion & Nicotine

Participants not responsive to nicotine patches who are randomly assigned at week 4 to use of Zyban (bupropion) in combination with nicotine patches

Group Type ACTIVE_COMPARATOR

Nicotine patches, then bupropion & nicotine patches (Post-Quit)

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.

Post-Quit Rescue to Varenicline

Participants not responsive to nicotine patches who are randomly assigned at week 4 to use of Chantix (varenicline)

Group Type ACTIVE_COMPARATOR

Nicotine patches, then varenicline (Post-Quit)

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks)

Post-Quit Rescue to Nicotine

Participants not responsive to nicotine patches who are randomly assigned at week 4 to continued use of nicotine patches

Group Type ACTIVE_COMPARATOR

Nicotine patches, then nicotine patches (Post-Quit)

Intervention Type DRUG

21mg (1 patch) or 42mg (2 patches) nicotine patches for first seven weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Interventions

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Nicotine Patches

21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Intervention Type DRUG

Nicotine patches, then bupropion & nicotine patches (Pre-Quit)

21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches)nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.

Intervention Type DRUG

Nicotine patches, then varenicline (Pre-Quit)

21mg (1 patch) or 42mg (2 patches) nicotine patches for first week (# of daily patches based on baseline carbon monoxide level); starting with week 2: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks)

Intervention Type DRUG

Nicotine patches, then nicotine patches (Pre-Quit)

21mg (1 patch) or 42mg (2 patches)nicotine patches for first five weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Intervention Type DRUG

Nicotine patches, then bupropion & nicotine patches (Post-Quit)

21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 150mg of bupropion once daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for first 3 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg (1 patch) or 42mg (2 patches) nicotine patches for 3 weeks and 4 days (# of daily patches based on baseline carbon monoxide level); 150mg of bupropion twice daily and 21mg nicotine patch for 4 weeks; 150mg of bupropion twice daily and 14mg nicotine patch for 2 weeks and 150mg of bupropion twice daily and 7mg nicotine patch for 2 weeks.

Intervention Type DRUG

Nicotine patches, then varenicline (Post-Quit)

21mg (1 patch) or 42mg (2 patches) nicotine patches for first three weeks (# of daily patches based on baseline carbon monoxide level); starting with week 4: 0.5mg of varenicline once daily for first 3 days; 0.5mg of varenicline twice daily for the next 4 days; and 1mg of varenicline twice daily for the remainder of the study (11 weeks)

Intervention Type DRUG

Nicotine patches, then nicotine patches (Post-Quit)

21mg (1 patch) or 42mg (2 patches) nicotine patches for first seven weeks (# of daily patches based on baseline carbon monoxide level); 21mg nicotine patch for 4 weeks; 14mg nicotine patch for 2 weeks and 7mg nicotine patch for 2 weeks.

Intervention Type DRUG

Other Intervention Names

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NicoDermCQ Zyban NicoDermCQ Chantix NicoDermCQ NicoDermCQ Zyban NicoDermCQ Chantix NicoDermCQ NicoDermCQ

Eligibility Criteria

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Inclusion Criteria

* 18-65 years old
* smoked an average of at least 10 cigarettes per day for three cumulative years of a brand that delivers (by Federal Trade Commission rated yields) at least 0.5mg nicotine
* expired carbon monoxide reading of at least 15ppm
* express a desire to quit smoking in the next 30 days

Exclusion Criteria

* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
* Hypotension (systolic \<90 mm Hg, diastolic \<60 mm Hg).
* Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician or physician assistant determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety.
* Coronary heart disease;
* Lifetime history of heart attack;
* Cardiac rhythm disorder (irregular heart rhythm);
* Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
* Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
* History of skin allergy;
* Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
* Liver or kidney disorder (except kidney stones, gallstones);
* Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
* Active ulcers in the past 30 days;
* Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
* Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
* History of migraine headaches in the past 5 years;
* History of fainting;
* Problems giving blood samples;
* Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
* Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
* Other major medical condition;
* Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and ADHD);
* Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
* Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 ("Thoughts that you would be better off dead, or of hurting yourself in some way") will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment;
* Bulimia or anorexia;
* Pregnant or nursing mothers;
* Use (within the past 30 days) of:
* Illegal drugs (or if the urine drug screen is positive),
* Experimental (investigational) drugs;
* Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
* Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed)
* Smokeless tobacco (chewing tobacco, snuff), cigars or pipes;
* Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.
* Alcohol abuse - The AUDIT (Alcohol Use Disorders Identification Test) questionnaire will be used to assess alcohol abuse. Potential participants will be asked the first two questions on the AUDIT questionnaire during the phone screen. If the person scores "4" on both questions, a screening appointment will not be scheduled. During the screening session the entire AUDIT questionnaire will be administered. Females who score greater than or equal to 13 and males who score greater than or equal to 15 will be excluded from the study.
* Significant adverse reaction to Wellbutrin / Zyban or Chantix / Varenicline in the past
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Philip Morris USA, Inc.

INDUSTRY

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jed E Rose, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Duke Center for Nicotine & Smoking Cessation Research

Charlotte, Durham, Raleigh, Winston-Salem, North Carolina, United States

Site Status

Countries

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United States

References

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Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, Lindson N. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 10.1002/14651858.CD000031.pub6.

Reference Type DERIVED
PMID: 37230961 (View on PubMed)

Livingstone-Banks J, Fanshawe TR, Thomas KH, Theodoulou A, Hajizadeh A, Hartman L, Lindson N. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev. 2023 May 5;5(5):CD006103. doi: 10.1002/14651858.CD006103.pub8.

Reference Type DERIVED
PMID: 37142273 (View on PubMed)

Rose JE, Behm FM. Adapting smoking cessation treatment according to initial response to precessation nicotine patch. Am J Psychiatry. 2013 Aug;170(8):860-7. doi: 10.1176/appi.ajp.2013.12070919.

Reference Type DERIVED
PMID: 23640009 (View on PubMed)

Uhl GR, Walther D, Musci R, Fisher C, Anthony JC, Storr CL, Behm FM, Eaton WW, Ialongo N, Rose JE. Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances. Mol Psychiatry. 2014 Jan;19(1):50-4. doi: 10.1038/mp.2012.155. Epub 2012 Nov 6.

Reference Type DERIVED
PMID: 23128154 (View on PubMed)

Other Identifiers

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Pro00013846

Identifier Type: -

Identifier Source: org_study_id