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Project 2: Strategies for Reducing Nicotine Content in Cigarettes

Primary Purpose

Nicotine Dependence, Tobacco Smoking

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Normal Nicotine Control Group
Immediate Nicotine Reduction Group
Gradual Nicotine Reduction Group
Sponsored by
Wake Forest University Health Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Nicotine Dependence focused on measuring smoking, nicotine reduction

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age 18+
  2. Daily smokers who smoke an average of at least five cigarettes per day for at least 1 year
  3. Breath CO levels > 8 ppm (if ≤ 8 ppm, then NicAlert Strip level must indicate regular smoking)

Exclusion Criteria:

  1. Planned quit date in the next 30 days
  2. Currently seeking treatment for smoking cessation
  3. Currently using nicotine replacement therapies or other pharmacotherapies as cessation aid (non-cessation intermittent use acceptable)
  4. A quit attempt in the past 30 days resulting in greater than 3 days of abstinence
  5. Using other tobacco products or e-cigarettes more than 9 days in the past 30 days
  6. Significant unstable medical conditions (Any significant change in a serious medical condition occurring during the past 3 months including, cardiovascular disease, COPD, and cancer, as determined by the licensed medical professional at each site)
  7. Unstable psychiatric conditions (Any significant change in psychiatric symptoms during the past 3 months as determined by the licensed medical professional at each site)
  8. Schizophrenia and schizoaffective disorder
  9. Psychiatric medication changes (e.g., new prescriptions, changes in dosages, or discontinuation of medications) in the past 3 months that was a result of negative changes in symptoms.

  10. Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP

    1. Marijuana will be tested for but will not be an exclusionary criterion.
    2. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded.
    3. Participants failing the toxicology screen will be allowed to re-screen once.

  11. Blood alcohol level > 0.01

    a. Participants failing the blood alcohol screen will be allowed to re-screen once.

  12. Binge drinking alcohol (more than 9 days in the past 30 days, 4/5 drinks per day (female/male))
  13. Pregnant, trying to become pregnant or breastfeeding
  14. Predominant use of 'roll your own cigarettes'
  15. CO reading >80 ppm

  16. Systolic BP greater than or equal to 160

    a. Participants failing for blood pressure will be allowed to re-screen once.

  17. Diastolic BP greater than or equal to 100

    a. Participants failing for blood pressure will be allowed to re-screen once.

  18. Systolic BP below 90 and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)

    a. Participants failing for blood pressure will be allowed to re-screen once.

  19. Diastolic BP below 50 and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)

    a. Participants failing for blood pressure will be allowed to re-screen once.

  20. Heart rate greater than or equal to 105 bpm

    a. Participants failing for heart rate will be allowed to re-screen once.

  21. Heart rate lower than 45 bpm and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint)

    a. Participants failing for heart rate will be allowed to re-screen once.

  22. Indicating any suicidal ideation in the past month, suicide attempts in the past 5 years (if within past 5 to 10 years, requires physician approval), or score of >4 on the MINI suicide subscale
  23. Household member enrolled in the study concurrently.
  24. Inability to independently read and comprehend the consent form and other written study materials and measures because participants are required to complete parts of the protocol at home independently.
  25. Participated in prior study that involved reduced nicotine content cigarettes.
  26. Having participated in a research study during the past three months in a study that would impact baseline smoking or response to study products.

  27. Currently taking the following anticonvulsant medications:

    1. Phenytoin [Brand Name: Dilantin]
    2. Carbamazepine [Brand Name: Tegretol, Carbatrol, Equetro, Epitol]
    3. Oxcarbazepine [Brand Name: Trileptal]
    4. Primidone [Brand Name: Mysoline]
    5. Phenobarbital

  28. Currently taking the following medication:

    1. Bendamustine (Treanda)
    2. Clopidogrel (Plavix)
    3. Clozapine (Clozaril, FazaClo)
    4. Erlotinib (Tarceva)
    5. Flecainide (Tambocor)
    6. Fluvoxamine (Luvox)
    7. Irinotecan (Camptosar)
    8. Olanzapine (Zyprexa)
    9. Ropinirole (Requip)
    10. Tacrine (Cognex)
    11. Theophylline (Theo Dur, etc.)

Sites / Locations

  • Mayo Clinic
  • University of California San Francisco
  • Moffitt Cancer Center
  • Johns Hopkins University
  • University of Minnesota Medical School Duluth
  • University of Minnesota
  • Duke University
  • Oregon Research Institute
  • University of Pennsylvania
  • MDAnderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Experimental

Experimental

Arm Label

Normal Nicotine Control Group

Immediate Nicotine Reduction Group

Gradual Nicotine Reduction Group

Arm Description

These subjects will smoke normal nicotine content Spectrum brand cigarettes for 20 weeks.

This group will immediately be switched to smoking very low nicotine content (VLNC) Spectrum brand cigarettes. They will smoke these cigarettes for 20 weeks.

This group will smoke progressively lower nicotine content Spectrum brand cigarettes for a period of one month each until they end up smoking the same VLNC cigarettes as the immediate reduction group.

Outcomes

Primary Outcome Measures

Toxicant exposure pattern: Expired air carbon monoxide
Between group comparison of expired air carbon monoxide (CO) values at week 20 using baseline CO values as a covariate.
Toxicant exposure pattern: Urinary phenanthrene tetroal (Phe)
Between group comparison of urinary phenanthrene tetroal values at week 20 using baseline values as a covariate.
Toxicant exposure pattern: Urinary mercapturic acids of acrolein
Between group comparison of urinary mercapturic acid level at week 20 using baseline values as a covariate.

Secondary Outcome Measures

Nicotine exposure: Total nicotine equivalents (TNE)
Between group comparison of urinary total nicotine equivalents at week 20 using baseline values as a covariate.
Other toxicant exposure: Tobacco specific nitrosamines-Total NNAL and NNN
Between group comparison of urinary total NNAL and NNN levels at week 20 using baseline values as a covariate.
Effect biomarker: C-Reactive protein-high sensitivity as an inflammation biomarker
Between group comparison of C-Reactive protein levels in serum at week 20 using baseline values as a covariate.
Measure of acceptability: Retention in study
Between group comparison of early termination from the study.
Measure of acceptability: Non-compliance
Between group comparison of use of non-study tobacco products.
Effect biomarker: 8-epi-PGF2α as a biomarker for oxidative stress
Between group comparison of 8-epi-PGF2α at week 20 using baseline values as a covariate.
Effect biomarker: White blood cells count as inflammation biomarker
Between group comparison of white blood cell count at week 20 using baseline values as a covariate.
Nicotine exposure: Urinary cotinine
Between group comparison of urinary total nicotine equivalents at week 20 using baseline values as a covariate.

Full Information

First Posted
May 12, 2014
Last Updated
August 13, 2018
Sponsor
Wake Forest University Health Sciences
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT02139930
Brief Title
Project 2: Strategies for Reducing Nicotine Content in Cigarettes
Official Title
Project 2: Strategies for Reducing Nicotine Content in Cigarettes
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
September 2014 (undefined)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
March 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The main goal of this project is to compare two different approaches to reducing levels of nicotine in cigarettes: an immediate reduction in nicotine content in cigarettes to non-addictive levels or a gradual reduction in nicotine content in cigarettes to non-addictive levels. These two approaches will then be contrasted to a group that continues to smoke cigarettes with nicotine content similar to conventional cigarettes.
Detailed Description
This project will be conducted to compare product use patterns and biomarkers of exposure between smokers who are assigned to a) gradual reduction in reduced nicotine content (RNC) cigarettes; b) immediate reduction to very low nicotine content (VLNC) cigarettes or c) normal nicotine content (NNC) cigarettes. The outcomes from this study will provide information on different approaches to reducing levels of nicotine in cigarettes and will determine the approach with the most optimal outcomes taking into account the balance between overall risk reduction (possibly maximized by abrupt switching) and compliance and acceptability (possibly maximized by gradual reduction of RNC cigarettes).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Dependence, Tobacco Smoking
Keywords
smoking, nicotine reduction

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1250 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Normal Nicotine Control Group
Arm Type
Active Comparator
Arm Description
These subjects will smoke normal nicotine content Spectrum brand cigarettes for 20 weeks.
Arm Title
Immediate Nicotine Reduction Group
Arm Type
Experimental
Arm Description
This group will immediately be switched to smoking very low nicotine content (VLNC) Spectrum brand cigarettes. They will smoke these cigarettes for 20 weeks.
Arm Title
Gradual Nicotine Reduction Group
Arm Type
Experimental
Arm Description
This group will smoke progressively lower nicotine content Spectrum brand cigarettes for a period of one month each until they end up smoking the same VLNC cigarettes as the immediate reduction group.
Intervention Type
Behavioral
Intervention Name(s)
Normal Nicotine Control Group
Intervention Description
Participants will smoke experimental cigarettes for a period of 20-weeks.
Intervention Type
Behavioral
Intervention Name(s)
Immediate Nicotine Reduction Group
Intervention Description
Participants will smoke experimental cigarettes for a period of 20-weeks.
Intervention Type
Behavioral
Intervention Name(s)
Gradual Nicotine Reduction Group
Intervention Description
Participants will smoke experimental cigarettes for a period of 20-weeks.
Primary Outcome Measure Information:
Title
Toxicant exposure pattern: Expired air carbon monoxide
Description
Between group comparison of expired air carbon monoxide (CO) values at week 20 using baseline CO values as a covariate.
Time Frame
20-week treatment period
Title
Toxicant exposure pattern: Urinary phenanthrene tetroal (Phe)
Description
Between group comparison of urinary phenanthrene tetroal values at week 20 using baseline values as a covariate.
Time Frame
20-week treatment period
Title
Toxicant exposure pattern: Urinary mercapturic acids of acrolein
Description
Between group comparison of urinary mercapturic acid level at week 20 using baseline values as a covariate.
Time Frame
20-week treatment period
Secondary Outcome Measure Information:
Title
Nicotine exposure: Total nicotine equivalents (TNE)
Description
Between group comparison of urinary total nicotine equivalents at week 20 using baseline values as a covariate.
Time Frame
End of treatment (Week 20)
Title
Other toxicant exposure: Tobacco specific nitrosamines-Total NNAL and NNN
Description
Between group comparison of urinary total NNAL and NNN levels at week 20 using baseline values as a covariate.
Time Frame
End of treatment (Week 20)
Title
Effect biomarker: C-Reactive protein-high sensitivity as an inflammation biomarker
Description
Between group comparison of C-Reactive protein levels in serum at week 20 using baseline values as a covariate.
Time Frame
End of treatment (Week 20)
Title
Measure of acceptability: Retention in study
Description
Between group comparison of early termination from the study.
Time Frame
End of treatment (Week 20)
Title
Measure of acceptability: Non-compliance
Description
Between group comparison of use of non-study tobacco products.
Time Frame
End of treatment (Week 20)
Title
Effect biomarker: 8-epi-PGF2α as a biomarker for oxidative stress
Description
Between group comparison of 8-epi-PGF2α at week 20 using baseline values as a covariate.
Time Frame
End of treatment (Week 20)
Title
Effect biomarker: White blood cells count as inflammation biomarker
Description
Between group comparison of white blood cell count at week 20 using baseline values as a covariate.
Time Frame
End of treatment (Week 20)
Title
Nicotine exposure: Urinary cotinine
Description
Between group comparison of urinary total nicotine equivalents at week 20 using baseline values as a covariate.
Time Frame
End of treatment (Week 20)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18+ Daily smokers who smoke an average of at least five cigarettes per day for at least 1 year Breath CO levels > 8 ppm (if ≤ 8 ppm, then NicAlert Strip level must indicate regular smoking) Exclusion Criteria: Planned quit date in the next 30 days Currently seeking treatment for smoking cessation Currently using nicotine replacement therapies or other pharmacotherapies as cessation aid (non-cessation intermittent use acceptable) A quit attempt in the past 30 days resulting in greater than 3 days of abstinence Using other tobacco products or e-cigarettes more than 9 days in the past 30 days Significant unstable medical conditions (Any significant change in a serious medical condition occurring during the past 3 months including, cardiovascular disease, COPD, and cancer, as determined by the licensed medical professional at each site) Unstable psychiatric conditions (Any significant change in psychiatric symptoms during the past 3 months as determined by the licensed medical professional at each site) Schizophrenia and schizoaffective disorder Psychiatric medication changes (e.g., new prescriptions, changes in dosages, or discontinuation of medications) in the past 3 months that was a result of negative changes in symptoms. Positive toxicology screen for any of the following drugs: cocaine, opiates, methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP Marijuana will be tested for but will not be an exclusionary criterion. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates, amphetamines or methadone will not be excluded. Participants failing the toxicology screen will be allowed to re-screen once. Blood alcohol level > 0.01 a. Participants failing the blood alcohol screen will be allowed to re-screen once. Binge drinking alcohol (more than 9 days in the past 30 days, 4/5 drinks per day (female/male)) Pregnant, trying to become pregnant or breastfeeding Predominant use of 'roll your own cigarettes' CO reading >80 ppm Systolic BP greater than or equal to 160 a. Participants failing for blood pressure will be allowed to re-screen once. Diastolic BP greater than or equal to 100 a. Participants failing for blood pressure will be allowed to re-screen once. Systolic BP below 90 and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint) a. Participants failing for blood pressure will be allowed to re-screen once. Diastolic BP below 50 and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint) a. Participants failing for blood pressure will be allowed to re-screen once. Heart rate greater than or equal to 105 bpm a. Participants failing for heart rate will be allowed to re-screen once. Heart rate lower than 45 bpm and symptomatic (dizziness, extreme fatigue, difficulty thinking, inability to stand or walk, feeling faint) a. Participants failing for heart rate will be allowed to re-screen once. Indicating any suicidal ideation in the past month, suicide attempts in the past 5 years (if within past 5 to 10 years, requires physician approval), or score of >4 on the MINI suicide subscale Household member enrolled in the study concurrently. Inability to independently read and comprehend the consent form and other written study materials and measures because participants are required to complete parts of the protocol at home independently. Participated in prior study that involved reduced nicotine content cigarettes. Having participated in a research study during the past three months in a study that would impact baseline smoking or response to study products. Currently taking the following anticonvulsant medications: Phenytoin [Brand Name: Dilantin] Carbamazepine [Brand Name: Tegretol, Carbatrol, Equetro, Epitol] Oxcarbazepine [Brand Name: Trileptal] Primidone [Brand Name: Mysoline] Phenobarbital Currently taking the following medication: Bendamustine (Treanda) Clopidogrel (Plavix) Clozapine (Clozaril, FazaClo) Erlotinib (Tarceva) Flecainide (Tambocor) Fluvoxamine (Luvox) Irinotecan (Camptosar) Olanzapine (Zyprexa) Ropinirole (Requip) Tacrine (Cognex) Theophylline (Theo Dur, etc.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Donny, PhD
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33617
Country
United States
Facility Name
Johns Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
University of Minnesota Medical School Duluth
City
Duluth
State/Province
Minnesota
ZIP/Postal Code
55812
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Oregon Research Institute
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97403
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
MDAnderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30193275
Citation
Hatsukami DK, Luo X, Jensen JA, al'Absi M, Allen SS, Carmella SG, Chen M, Cinciripini PM, Denlinger-Apte R, Drobes DJ, Koopmeiners JS, Lane T, Le CT, Leischow S, Luo K, McClernon FJ, Murphy SE, Paiano V, Robinson JD, Severson H, Sipe C, Strasser AA, Strayer LG, Tang MK, Vandrey R, Hecht SS, Benowitz NL, Donny EC. Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial. JAMA. 2018 Sep 4;320(9):880-891. doi: 10.1001/jama.2018.11473.
Results Reference
derived

Learn more about this trial

Project 2: Strategies for Reducing Nicotine Content in Cigarettes

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