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Adaptive Pharmacotherapy for Smoking Cessation

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ClinicalTrials.gov Identifier: NCT02501265
Recruitment Status : Recruiting
First Posted : July 17, 2015
Last Update Posted : October 18, 2018
Sponsor:
Collaborators:
National Institute on Drug Abuse (NIDA)
Pfizer
Information provided by (Responsible Party):
Duke University

Brief Summary:
The purpose of this study is to assess an "adaptive" approach to smoking cessation pharmacotherapy. The protocol is designed to compare adaptive vs. standard approaches to two common smoking cessation pharmacotherapies - Varenicline (commonly known as Chantix) and the Nicotine Patch. The investigators hypothesize that participants allocated to adaptive therapy will show significantly higher biochemically confirmed 30-day continuous abstinence at 12 weeks post-Target Quit Day (TQD).

Condition or disease Intervention/treatment Phase
Nicotine Dependence Behavioral: Varenicline Standard Protocol Behavioral: Nicotine Patch Standard Protocol Drug: Varenicline Adaptive Protocol Drug: Nicotine Adaptive Protocol Phase 2

Detailed Description:
The purpose of this study is to assess an "adaptive" approach to smoking cessation pharmacotherapy. The protocol is designed to compare adaptive vs. standard approaches to two common smoking cessation pharmacotherapies (Varenicline and Nicotine Patch). The adaptive treatment approach provides the addition of Bupropion in the pre-quit period for participants who are not "responding" to initial treatment. Little is known about the adaptive use of Varenicline or Nicotine Patch, in which Bupropion is added to Varenicline or Patch for those who do not respond to one of these medications in a pre-quit treatment period. This study attempts to address these knowledge deficits. The study (N=300) is a double-blinded randomized placebo-controlled trial designed to compare biochemically-confirmed abstinence rates in smokers randomized to Varenicline Adaptive Protocol vs. Varenicline (N=150) and for comparison, Nicotine Patch Adaptive Protocol vs. Nicotine Patch (N=150). The "Varenicline Adaptive Protocol" is conducted by starting treatment with Varenicline 4 weeks prior to the quit day and following each participant's response to this pre-treatment medication. After 2 weeks, if the patient shows a reduction greater than 50% in cigarettes smoked per day, then the patient is considered to be a "Varenicline responder" and is continued on Varenicline alone out to 12-weeks post quit day. If the patient does not spontaneously decrease smoking in the pre-quit period by more than 50% cigarettes per day, the patient is considered to be a "Varenicline non-responder" and Bupropion is added to the Varenicline. For comparison, an identical protocol is used with nicotine patch vs. nicotine patch adaptive treatment. The study uses only FDA-approved medications: Varenicline, Nicotine Patch, Bupropion, and placebo controls. To pattern clinical practice, participants will be able to choose whether they would like to use a patch or Varenicline-based treatment. After choosing, however, they will be randomized to adaptive vs. non-adaptive version of that treatment. Placebo medications are matched throughout the study. Participants will be blinded to all medications. All participants will receive behavioral treatment including a single 40-minute visit with a medical provider. The study is designed to provide researchers and clinicians with a better understanding of how to use adaptive pharmacotherapy protocols to improve smoking cessation rates.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study (N=300) is a double-blinded randomized placebo-controlled trial designed to compare biochemically-confirmed abstinence rates in smokers randomized to Varenicline Adaptive Protocol vs. Varenicline (N=150) and for comparison, Nicotine Patch Adaptive Protocol vs. Nicotine Patch (N=150).
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized Controlled Smoking Cessation Trial on Adaptive Pharmacotherapy
Actual Study Start Date : June 6, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Varenicline Standard Protocol
Participant choses Varenicline-based treatment and is then randomized to Standard Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts placebo Varenicline. Consistent with Varenicline Standard Treatment, 1 week prior to the TQD the participant will switch to active Varenicline and placebo Bupropion. Participant will continue active Varenicline and placebo Bupropion to 12 weeks post-TQD.
Behavioral: Varenicline Standard Protocol

4 weeks pre-TQD: Start Placebo Varenicline

1 week prior to TQD: Switch to Active Varenicline

1 week prior to TQD: Start Placebo Bupropion Varenicline + Placebo Bupropion to 12 weeks post TQD

Other Name: Standard Varenicline

Active Comparator: Nicotine Patch Standard Protocol
Participant choses Nicotine patch-based treatment and is then randomized to Standard Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts placebo Nicotine Patch. One week prior to TQD, participant will start placebo Bupropion. Consistent with Nicotine Patch Standard Treatment, participant will start active Nicotine Patch on TQD. Participant will continue active Nicotine Patch and placebo Bupropion to 12 weeks post-TQD.
Behavioral: Nicotine Patch Standard Protocol

4 weeks pre-TQD: Start Placebo Nicotine Patch TQD: Start active Nicotine Patch

1 week prior to TQD: Start Placebo Bupropion Nicotine Patch + Placebo Bupropion to 12 weeks post TQD

Other Name: Standard Nicotine Patch

Experimental: Varenicline Adaptive Protocol
Participant chooses Varenicline treatment and is randomized to Adaptive Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts active Varenicline. Two weeks prior to TQD, cigarettes smoked per day is assessed. If the number of cigarettes smoked per day is reduced by >50%, the participant is considered a Varenicline responder, and starts placebo Bupropion 1 week prior to the TQD. If the participant DOES NOT reduce cigarettes smoked per day by >50%, the participant is considered a Varenicline non-responder and starts active Bupropion 1 week prior to TQD. Varenicline responders will continue active Varenicline and placebo Bupropion to 12 weeks post TQD. Varenicline non-responders will continue active Varenicline and active Bupropion to 12 weeks post TQD.
Drug: Varenicline Adaptive Protocol

VARENICLINE RESPONDER 4 weeks pre-TQD: Start Varenicline 2 weeks pre-TQD: DOES reduce cigs/day by > 50% 1 week pre-TQD: Start Placebo Bupropion Varenicline + Placebo Bupropion to 12 weeks post TQD

VARENICLINE NON-RESPONDER 4 weeks pre-TQD: Start Varenicline 2 weeks pre-TQD: DOES NOT reduce cigs/day by > 50%

1 week pre-TQD: Start active Bupropion Varenicline + Bupropion to 12 weeks post TQD

Other Name: Adaptive Varenicline

Experimental: Nicotine Patch Adaptive Protocol
Participant choses Nicotine treatment and is randomized to Adaptive Treatment arm (N=75). Four weeks prior to target quit date (TQD), participant starts active Nicotine Patches. Two weeks prior to TQD, cigarettes smoked per day is assessed. If cigarettes smoked per day is reduced by >50%, the participant is considered a Nicotine Patch responder and starts placebo Bupropion 1 week prior to the TQD. If the participant DOES NOT reduce cigarettes smoked per day by >50%, the participant is considered a Nicotine Patch non-responder and starts active Bupropion 1 week prior to the TQD. Nicotine Patch responders will continue active Nicotine Patches and placebo Bupropion to 12 weeks post TQD. Nicotine Patch non-responders will continue active Nicotine Patches and Bupropion to 12 weeks post TQD.
Drug: Nicotine Adaptive Protocol

NICOTINE PATCH RESPONDER 4 weeks pre-TQD: Start Patch 2 weeks pre-TQD: DOES reduce cigs/day by > 50% 1 week pre-TQD: Start Placebo Bupropion Patch + Placebo Bupropion to 12 weeks post TQD

NICOTINE PATCH NON-RESPONDER 4 weeks pre-TQD: Start Patch 2 weeks pre-TQD: DOES NOT reduce cigs/day by > 50%

1 week pre-TQD: Start Bupropion Patch + Bupropion to 12 weeks post TQD

Other Name: Adaptive Nicotine




Primary Outcome Measures :
  1. Biochemically-confirmed 30-day continuous smoking abstinence [ Time Frame: 12 weeks post-Target Quit Day (TQD) ]
    Biochemically-confirmed 30-day continuous smoking abstinence at 12-weeks post quit attempt measured by self-report and confirmed by carbon monoxide (CO) expired breath testing with CO < 7ppm required to confirm abstinence. Subject will be coded as abstinent only if he or she meets criteria for both self-reported abstinence and biochemical abstinence.


Secondary Outcome Measures :
  1. 7-day point prevalence biochemically confirmed abstinence [ Time Frame: 2 weeks post-TQD ]
    7-day point prevalence biochemically confirmed abstinence rates at 2 weeks post-TQD in participants randomized to adaptive vs standard treatment. Measures: Carbon Monoxide Breath Testing < 7 ppm and a 7 day diary of cigarette use completed prior to in-person visits.

  2. 7-day point prevalence biochemically confirmed abstinence [ Time Frame: 12 weeks post-TQD ]
    7-day point prevalence biochemically confirmed abstinence rates at 12 weeks post-TQD in participants randomized to adaptive vs standard treatment. Measures: Carbon Monoxide Breath Testing < 7 ppm and a 7 day diary of cigarette use completed prior to in-person visits.

  3. Phone-assessed self-reported abstinence [ Time Frame: 1 week post-TQD ]
    Phone-assessed self-reported abstinence at 1 week post-TQD in participants randomized to adaptive vs standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling. This includes phone-based assessment of single-item question on smoking during the last 24 hours.

  4. Phone-assessed self-reported abstinence [ Time Frame: 2 weeks post-TQD ]
    Phone-assessed self-reported abstinence at 2 weeks post-TQD in participants randomized to adaptive vs standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling. This includes phone-based assessment of single-item question on smoking over the last 7 days.

  5. Phone-assessed self-reported abstinence [ Time Frame: 6 weeks post-TQD ]
    Phone-assessed self-reported abstinence at 6 weeks post-TQD in participants randomized to adaptive vs standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling. This includes phone-based assessment of single-item question on smoking over the last 7 days.

  6. Phone-assessed self-reported abstinence [ Time Frame: 12 weeks post-TQD ]
    Phone-assessed self-reported abstinence at 12 weeks post-TQD in participants randomized to adaptive vs standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling. This includes phone-based assessment of single-item question on smoking over the last 7 days.

  7. Phone-assessed self-reported abstinence [ Time Frame: 26 weeks post-TQD ]
    Phone-assessed self-reported abstinence at 26 weeks post-TQD in participants randomized to adaptive vs standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling. This includes phone-based assessment of single-item question on smoking the last 30 days.

  8. Phone-assessed self-reported abstinence [ Time Frame: 52 weeks post-TQD ]
    Phone-assessed self-reported abstinence at 52 weeks post-TQD in participants randomized to adaptive vs standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling. This includes phone-based assessment of single-item question on smoking the last 30 days.

  9. Smoking reduction (number of cigarettes per day) - in person [ Time Frame: 2 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) measured at 2 weeks post TQD visit in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  10. Smoking reduction (number of cigarettes per day) - in person [ Time Frame: 12 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) at 12 weeks post TQD visit in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  11. Phone-assessed smoking reduction (number of cigarettes per day) [ Time Frame: 1 week post-TQD ]
    Smoking reduction (number of cigarettes per day) via phone-based self-report at 1 week post-TQD in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  12. Phone-assessed smoking reduction (number of cigarettes per day) [ Time Frame: 2 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) via phone-based self-report at 2 weeks post-TQD in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  13. Phone-assessed smoking reduction (number of cigarettes per day) [ Time Frame: 6 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) via phone-based self-report at 6 weeks post-TQD in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  14. Phone-assessed smoking reduction (number of cigarettes per day) [ Time Frame: 12 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) via phone-based self-report at 12 weeks post-TQD in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  15. Phone-assessed smoking reduction (number of cigarettes per day) [ Time Frame: 26 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) via phone-based self-report at 26 weeks post-TQD in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  16. Phone-assessed smoking reduction (number of cigarettes per day) [ Time Frame: 52 weeks post-TQD ]
    Smoking reduction (number of cigarettes per day) via phone-based self-report at 52 weeks post-TQD in participants randomized to adaptive vs. standard treatment. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  17. Change in Fagerstrom Test for Nicotine Dependence (FTND) score - in person [ Time Frame: Measured at week 0, 2 weeks pre-TQD, 2 weeks post-TQD and 12 weeks post-TQD ]
    Change in Fagerstrom Test for Nicotine Dependence (FTND) scores at baseline (pre-quit) to 2- and 12-weeks post-TQD. If found to change significantly from baseline to a post-quit time point, it will be assessed as possible mediator of abstinence outcomes. FTND scores are evaluated on a scale from 0-10, with greater scores indicating higher nicotine dependence.

  18. Change in Perceived Stress Scale (PSS-4) score - in person [ Time Frame: Measured at week 0, 2 weeks pre-TQD, 2 weeks post-TQD and 12 weeks post-TQD ]
    Change in Perceived Stress Scale (PSS-4) score at baseline (pre-quit) to 2- and 12-weeks post TQD on stress. If found to change significantly from baseline to a post quit time point, it will be assessed as possible mediator of abstinence outcomes. PSS-4 scores are evaluated on a scale from 0-16, with higher scores indicating greater stress.

  19. Change in Generalized Anxiety Disorder (GAD-2) scale score - in person [ Time Frame: Measured at week 0, 2 weeks pre-TQD, 2 weeks post-TQD and 12 weeks post-TQD ]
    Change in Generalized Anxiety Disorder (GAD-2) scale score at baseline (pre-quit) to 2- and 12-weeks post TQD on anxiety. If found to change significantly from baseline to a post quit time point, it will be assessed as possible mediator of abstinence outcomes. GAD-2 scores are evaluated on a scale from 0-6, with scores of 3 or greater indicating a positive screen for general anxiety disorder.

  20. Change in Patient Health Questionnaire (PHQ-2) score - in person [ Time Frame: Measured at week 0, 2 weeks pre-TQD, 2 weeks post-TQD and 12 weeks post-TQD ]
    Change in Patient Health Questionnaire (PHQ-2) score at baseline (pre-quit) to 2- and 12-weeks post TQD on depression. If found to change significantly from baseline to a post quit time point, it will be assessed as possible mediator of abstinence outcomes. PHQ-2 scores are evaluated on a scale from 0-6, with scores of 3 or greater indicating a positive screen for depression.

  21. Change in self-reported self-efficacy and motivation to quit smoking - in person [ Time Frame: Measured at week 0, 2 weeks pre-TQD, 2 weeks post-TQD and 12 weeks post-TQD ]
    Change in self-reported self-efficacy and motivation to quit smoking at baseline (pre-quit) to 2- and 12-weeks post TQD. If found to change significantly from baseline to a post quit time point, it will be assessed as possible mediator of abstinence outcomes. Measured using two non-standardized questions on self-efficacy and motivation to quit smoking on a scale from 1-7, with higher numbers indicating higher self-efficacy and motivation.

  22. Phone-assessed smoking urges [ Time Frame: Measured at 1, 2, 6, 12, 26 and 52 weeks post-TQD ]
    Phone-assessed non-standardized single item questions on urges. If found to change significantly from baseline to a post quit time point, it will be assessed as a possible mediator of abstinence outcomes. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  23. Phone-assessed withdrawal symptoms [ Time Frame: Measured at 1, 2, 6, 12, 26 and 52 weeks post-TQD ]
    Phone-assessed non-standardized single item questions on withdrawal. If found to change significantly from baseline to a post quit time point, it will be assessed as a possible mediator of abstinence outcomes. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  24. Phone-assessed motivation to quit smoking or remain abstinent [ Time Frame: Measured at 1, 2, 6, 12, 26 and 52 weeks post-TQD ]
    Phone-assessed non-standardized single item questions on motivation to quit smoking or remain abstinent. If found to change significantly from baseline to a post quit time point, it will be assessed as a possible mediator of abstinence outcomes. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  25. Phone-assessed confidence in ability to quit or remain abstinent [ Time Frame: Measured at 1, 2, 6, 12, 26 and 52 weeks post-TQD ]
    Phone-assessed non-standardized single item questions on confidence in ability to quit or remain abstinent. If found to change significantly from baseline to a post quit time point, it will be assessed as a possible mediator of abstinence outcomes. Phone assessments will be compared at specific time points and also across multiple time points using multi-level modeling.

  26. Baseline General Anxiety Disorder (GAD-2) scores - in person [ Time Frame: 0 Weeks to 2 Weeks ]
    Baseline General Anxiety Disorder (GAD-2) scores for their effect on allocation to Responder or Non-Responder status in the adaptive and standard treatment arms. GAD-2 scores are evaluated on a scale from 0-6, with scores of 3 or greater indicating a positive screen for general anxiety disorder.

  27. Baseline Patient health Questionnaire (PHQ-2) scores - in person [ Time Frame: 0 Weeks to 2 Weeks ]
    Baseline Patient health Questionnaire (PHQ-2) scores for their effect on allocation to Responder or Non-Responder status in the adaptive and standard treatment arms. PHQ-2 scores are evaluated on a scale from 0-6, with scores of 3 or greater indicating a positive screen for depression.

  28. Baseline Perceived Stress Scale (PSS-4) scores - in person [ Time Frame: 0 Weeks to 2 Weeks ]
    Baseline Perceived Stress Scale (PSS-4) scores for their effect on allocation to Responder or Non-Responder status in the adaptive and standard treatment arms. PSS-4 scores are evaluated on a scale from 0-16, with higher scores indicating greater stress.

  29. Cost-benefit analyses based on work absenteeism [ Time Frame: Measured at week 0, 2 weeks pre-TQD, 2 weeks post-TQD and 12 weeks post-TQD ]
    Cost-benefit analyses comparing adaptive vs. standard groups based on non-standardized questionnaire of work days missed as well as frequency and duration of smoke-breaks at work. These data points will be assessed at specific time points and also across multiple time points.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Age 18 years or older
  2. Actively smoking 5 or more cigarettes per day for at least one year
  3. Fluency in spoken and written English
  4. Willing to set a quit date within 6 weeks
  5. Access to a telephone
  6. Willingness to take Varenicline OR nicotine patch (patient choice)
  7. Willingness to take Bupropion

Exclusion Criteria

  1. Daily use of a second form of tobacco or nicotine (e.g. e-cigarettes, cigars, chewing tobacco, snuff).
  2. Current use of a smoking cessation medication (e.g. nicotine replacement, Varenicline, Bupropion).
  3. Report of pregnancy, attempting to get pregnant, or actively breast feeding or positive urine pregnancy test (only given to females with child bearing potential).
  4. Additional criteria may apply.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02501265


Contacts
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Contact: Leah Thomas, CRC 919-668-9378 leah.thomas@duke.edu

Locations
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United States, North Carolina
Duke Center for Smoking Cessation Recruiting
Durham, North Carolina, United States, 27705
Contact: Jed Rose, Ph.D.    919-668-5055      
Sponsors and Collaborators
Duke University
National Institute on Drug Abuse (NIDA)
Pfizer
Investigators
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Principal Investigator: James M Davis, M.D. Duke University

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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02501265     History of Changes
Other Study ID Numbers: Pro00072077
P50DA027840 ( U.S. NIH Grant/Contract )
First Posted: July 17, 2015    Key Record Dates
Last Update Posted: October 18, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Duke University:
Nicotine addiction
Cigarette smoking
Bupropion
Varenicline
Adaptive Approach
Nicotine Patch
Chantix

Additional relevant MeSH terms:
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Tobacco Use Disorder
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Nicotine
Varenicline
Bupropion
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Agents
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors