Overview

This trial is active, not recruiting.

Conditions nicotine dependence, tobacco smoking
Treatments normal nicotine control group, immediate nicotine reduction group, gradual nicotine reduction group
Phase phase 3
Sponsor University of Pittsburgh
Collaborator National Institute on Drug Abuse (NIDA)
Start date September 2014
End date March 2017
Trial size 1250 participants
Trial identifier NCT02139930, U54DA031659, U54DA031659-P2

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose basic science
Arm
(Active Comparator)
These subjects will smoke normal nicotine content Spectrum brand cigarettes for 20 weeks.
normal nicotine control group
Participants will smoke experimental cigarettes for a period of 20-weeks.
(Experimental)
This group will immediately be switched to smoking very low nicotine content (VLNC) Spectrum brand cigarettes. They will smoke these cigarettes for 20 weeks.
immediate nicotine reduction group
Participants will smoke experimental cigarettes for a period of 20-weeks.
(Experimental)
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.
gradual nicotine reduction group
Participants will smoke experimental cigarettes for a period of 20-weeks.

Primary Outcomes

Measure
Toxicant exposure pattern: Expired air carbon monoxide
time frame: 20-week treatment period
Toxicant exposure pattern: Urinary phenanthrene tetroal (Phe)
time frame: 20-week treatment period
Toxicant exposure pattern: Urinary mercapturic acids of acrolein
time frame: 20-week treatment period

Secondary Outcomes

Measure
Nicotine exposure: Total nicotine equivalents (TNE)
time frame: End of treatment (Week 20)
Other toxicant exposure: Tobacco specific nitrosamines-Total NNAL and NNN
time frame: End of treatment (Week 20)
Effect biomarker: C-Reactive protein-high sensitivity as an inflammation biomarker
time frame: End of treatment (Week 20)
Measure of acceptability: Retention in study
time frame: End of treatment (Week 20)
Measure of acceptability: Non-compliance
time frame: End of treatment (Week 20)
Effect biomarker: 8-epi-PGF2α as a biomarker for oxidative stress
time frame: End of treatment (Week 20)
Effect biomarker: White blood cells count as inflammation biomarker
time frame: End of treatment (Week 20)
Nicotine exposure: Urinary cotinine
time frame: End of treatment (Week 20)

Eligibility Criteria

Male or female participants at least 18 years old.

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.)

Additional Information

Official title Project 2: Strategies for Reducing Nicotine Content in Cigarettes
Principal investigator Eric Donny, PhD
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).
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by University of Pittsburgh.