Project 2 Cigarette and E-cigarette Nicotine Content and E-liquid Flavors

Project 2: The Impact of Cigarette Nicotine Content, E-cigarette Nicotine Content, and E-cigarette Flavoring on Smoking Behavior

Project 2 will evaluate the impact of very low nicotine content cigarettes, e-cigarette nicotine content, and e-cigarette flavoring on cigarettes smoked per day, nicotine exposure, puff topography, discomfort/dysfunction, other health-related behaviors, nicotine/tobacco dependence, biomarkers of tobacco exposure, intention to quit, compensatory smoking, other tobacco use, cardiovascular function, and perceived risk. Project 2 will also evaluate differences between conditions in compliance with product use and the ability to abstain from cigarette smoking when provided a financial incentive for abstinence from combusted tobacco. This is not a treatment program for smoking.

Study Overview

• Status: Completed
• Conditions: Smoking
• Intervention / Treatment: Other: NNC Spectrum Cigarette; Other: Moderate nicotine level e-liquid; Other: Tobacco Flavors; Other: Low nicotine level e-liquid; Other: Tobacco and non-tobacco e-liquid flavors; Other: VLNC Spectrum Cigarette

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27101
      • Wake Forest Biotech Place
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Smokers who have tried vaping multiple times.
• Generally good health.

Exclusion Criteria:

• If female, currently pregnant, trying to become pregnant or breastfeeding.
• Planning to quit smoking.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Normal Nicotine Content (NNC) cigarette + moderate nicotine e-liquid + tobacco flavors; Participants are provided with normal nicotine content tobacco Spectrum Cigarettes along with moderate nicotine level e-liquid cartridges and can choose from tobacco e-liquid flavors.	Other: NNC Spectrum Cigarette; Participants are provided with normal nicotine content Spectrum Cigarette for 13 weeks.; Other: Moderate nicotine level e-liquid; Participants are provided with moderate nicotine level e-liquid for 13 weeks; Other: Tobacco Flavors; Participants can choose e-liquid flavors from a selection of tobacco flavors
EXPERIMENTAL: NNC cigarette + low nicotine e-liquid + tobacco flavors; Participants are provided with normal nicotine content tobacco Spectrum Cigarettes along with very low nicotine level e-liquid cartridges and can choose from tobacco e-liquid flavors.	Other: NNC Spectrum Cigarette; Participants are provided with normal nicotine content Spectrum Cigarette for 13 weeks.; Other: Tobacco Flavors; Participants can choose e-liquid flavors from a selection of tobacco flavors; Other: Low nicotine level e-liquid; Participants are provided with very low or nicotine-free nicotine level e-liquid for 13 weeks
EXPERIMENTAL: NNC cigarette + moderate nicotine e-liquid + variety flavors; Participants are provided with normal nicotine content tobacco Spectrum Cigarettes along with moderate nicotine level e-liquid cartridges and can choose from tobacco and non-tobacco e-liquid flavors.	Other: NNC Spectrum Cigarette; Participants are provided with normal nicotine content Spectrum Cigarette for 13 weeks.; Other: Moderate nicotine level e-liquid; Participants are provided with moderate nicotine level e-liquid for 13 weeks; Other: Tobacco and non-tobacco e-liquid flavors; Participants can choose e-liquid flavors from a selection of flavors that includes tobacco and non-tobacco choices
EXPERIMENTAL: NNC cigarette + low nicotine e-liquid + variety flavors; Participants are provided with normal nicotine content tobacco Spectrum Cigarettes along with very low or nicotine-free nicotine level e-liquid cartridges and can choose from tobacco and non-tobacco e-liquid flavors	Other: NNC Spectrum Cigarette; Participants are provided with normal nicotine content Spectrum Cigarette for 13 weeks.; Other: Low nicotine level e-liquid; Participants are provided with very low or nicotine-free nicotine level e-liquid for 13 weeks; Other: Tobacco and non-tobacco e-liquid flavors; Participants can choose e-liquid flavors from a selection of flavors that includes tobacco and non-tobacco choices
EXPERIMENTAL: Very Low Nicotine Content (VLNC) cigarette + moderate nicotine e-liquid + tobacco flavor; Participants are provided with very low nicotine content tobacco Spectrum Cigarettes along with moderate nicotine level e-liquid cartridges and can choose from tobacco e-liquid flavors.	Other: Moderate nicotine level e-liquid; Participants are provided with moderate nicotine level e-liquid for 13 weeks; Other: Tobacco Flavors; Participants can choose e-liquid flavors from a selection of tobacco flavors; Other: VLNC Spectrum Cigarette; Participants are provided with very low nicotine content Spectrum Cigarette for13 weeks
EXPERIMENTAL: VLNC cigarette + low nicotine e-liquid +tobacco flavors; Participants are provided with very low nicotine content tobacco Spectrum Cigarettes along with very low or nicotine-free nicotine level e-liquid cartridges and can choose from tobacco e-liquid flavors.	Other: Tobacco Flavors; Participants can choose e-liquid flavors from a selection of tobacco flavors; Other: Low nicotine level e-liquid; Participants are provided with very low or nicotine-free nicotine level e-liquid for 13 weeks; Other: VLNC Spectrum Cigarette; Participants are provided with very low nicotine content Spectrum Cigarette for13 weeks
EXPERIMENTAL: VLNC cigarette + moderate nicotine e-liquid + variety flavors; Participants are provided with very low nicotine content tobacco Spectrum Cigarettes along with moderate nicotine level e-liquid cartridges and can choose from tobacco and non-tobacco e-liquid flavors.	Other: Moderate nicotine level e-liquid; Participants are provided with moderate nicotine level e-liquid for 13 weeks; Other: Tobacco and non-tobacco e-liquid flavors; Participants can choose e-liquid flavors from a selection of flavors that includes tobacco and non-tobacco choices; Other: VLNC Spectrum Cigarette; Participants are provided with very low nicotine content Spectrum Cigarette for13 weeks
EXPERIMENTAL: VLNC cigarette + low nicotine e-liquid + variety flavors; Participants are provided with very low or nicotine-free nicotine content tobacco Spectrum Cigarettes along with very low nicotine level e-liquid cartridges and can choose from tobacco and non-tobacco e-liquid flavors	Other: Low nicotine level e-liquid; Participants are provided with very low or nicotine-free nicotine level e-liquid for 13 weeks; Other: Tobacco and non-tobacco e-liquid flavors; Participants can choose e-liquid flavors from a selection of flavors that includes tobacco and non-tobacco choices; Other: VLNC Spectrum Cigarette; Participants are provided with very low nicotine content Spectrum Cigarette for13 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Cigarettes Smoked Per Day	The average number of cigarettes (study and non-study, summed) smoked per day between the Week 10 and Week 12 visits (the end of the study).	Week 10 through Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure of Cigarette Exposure Using Expired Carbon Monoxide (CO)	Measure of cigarette smoke exposure using data on expired breath CO. CO was captured using Covita Smokelyzer devices and standard exhalation procedures. The unit of measurement is parts per million (ppm).	Baseline - Week 12
Number of Subjects With Smoke Free Days	Study team generates the smoke free days outcome by counting days where no cigarettes and no other forms of combusted tobacco products are used. Days where participants use no nicotine products and days where participants only vape are "smoke free." Percentage of smoke free days = the number days that participants reported smoking 0 cigarettes (0 study cigarettes and 0 non-study cigarettes) divided by the total number of days between their randomization and Week 12 visits. Due to the distribution of the data, statisticians grouped participants according to whether they had 0 smoke-free days or more than 0 smoke free days during the study.	Baseline-Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Nicotine Withdrawal Scale	Measure of discomfort and dysfunction; 15-item self-reported scale to evaluate the effects of smoking cessation. Score ranges from 0 to 60 with higher score denoting more severe symptoms.	Baseline-Week 12
Number of Days Using Assigned Vaping Device	collected through Interactive Voice Response (IVR) Review	Baseline-Week 12
Cigarette Evaluation Scale	Assesses the extent to which the product they just sampled produced various subjective effects including satisfaction, good taste, dizziness, reduced appetite, nausea, and enjoyable sensations in the throat and chest. Score ranges from 1 to 91 with a higher score denoting more positive sensations.	Baseline-Week 12
Mercapturic Acids	Measure of toxicant exposure	Baseline-Week 12
Fagerstrom Nicotine Dependence Scale	Dependence Measure	Baseline-Week 12
Study Cigarettes Smoked Per Day	Study cigarettes smoked per day	Baseline-Week 12
IVR Review and Timeline Followback and E-liquid Accountability	Measure of vaping device use	Baseline-Week 12
Number of Choices to Smoke in Preference Assessment Task	Measure of relative reinforcement	Week 00
Purchase Task	Measure of relative reinforcement and substitution	Baseline, Week 12
Predicted Behavior Questionnaire	Measure of hypothetical cigarette and vaping device use	Week 12
IVR Review and Timeline Followback	Measure of compliance	Baseline-Week 12
Drop-out Rate	Drop-out rate	Baseline-Week 12
Urge to Use Questionnaire	Measure of discomfort and dysfunction	Baseline-Week 12
Center for Epidemiologic Studies Depression Scale	Measure of discomfort and dysfunction	Baseline, Weeks 04, 08, 12
Breath Alcohol	Alcohol use	Baseline - Week 12
Urine Drug Screen	Drug use	Baseline, Week 12
Alcohol Use Questionnaire	Alcohol use	Baseline-Week 12
Drug Use Questionnaire	Drug use	Baseline-Week 12
Weight	Weight	Baseline-Week 12
Urinary Anatabine Biomarker	Measure of cigarette exposure and compliance	Baseline -Week 12
Total Nicotine Equivalents	Measure of nicotine exposure	Baseline - Week 12
Environmental and Social Influences on Tobacco Use Questionnaire	Measure of smoking and vaping context	Baseline-Week 12
Context of Product Use Questionnaire	Measure of smoking and vaping context	Baseline-Week 12
Puff Topography	Measure of smoking and vaping topography	Weeks 01 and 10
Vaping Utility Questionnaire	Measure of product expectancy	Baseline, Week 12
Smoking and Vaping Expectancy Questionnaires	Measure of product expectancy	Baseline-Week 12
Cigarette and Product Evaluation Scale	Measure of product characteristics	Baseline-Week 12
Perceived Health Risk Questionnaire	Measure of perceived personal health risk	Baseline-Week 12
Penn State Smoking Dependence Questionnaire	Dependence Measure (smoking and vaping)	Baseline-Week 12
Primary Subscales From Brief Wisconsin Inventory of Smoking Dependence Motive (WISDM)	Dependence Measure	Baseline-Week 12
Population Assessment of Tobacco and Health (PATH) Smoking Dependence Questions	Dependence Measure (smoking and vaping)	Baseline-Week 12
Stages of Change	Measure of intention to quit	Baseline-Week 12
Contemplation Ladder	Measure of intention to quit	Baseline-Week 12
Quit Attempts	Measure of intention to quit	Baseline-Week 12
Post-intervention Changes in Tobacco Use Behavior	Measure of 30-day tobacco use post-intervention of study products	30 Day Follow up
Qualitative Interview	Themes related to product use patterns, e-liquid flavor selection, non-compliance and general study feedback	30 Day Follow up

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Drug Abuse (NIDA); University of Pennsylvania
• Investigators: Principal Investigator: Eric Donny, PhD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

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• Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, Jacob P 3rd. Progressive commercial cigarette yield reduction: biochemical exposure and behavioral assessment. Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):876-83. doi: 10.1158/1055-9965.EPI-08-0731. Epub 2009 Mar 3.
• Benowitz NL, Dains KM, Hall SM, Stewart S, Wilson M, Dempsey D, Jacob P 3rd. Smoking behavior and exposure to tobacco toxicants during 6 months of smoking progressively reduced nicotine content cigarettes. Cancer Epidemiol Biomarkers Prev. 2012 May;21(5):761-9. doi: 10.1158/1055-9965.EPI-11-0644. Epub 2012 Feb 21.
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• Dempsey D, Tutka P, Jacob P 3rd, Allen F, Schoedel K, Tyndale RF, Benowitz NL. Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther. 2004 Jul;76(1):64-72. doi: 10.1016/j.clpt.2004.02.011.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 6, 2018
• Primary Completion (ACTUAL): March 13, 2020
• Study Completion (ACTUAL): March 13, 2020

Study Registration Dates

• First Submitted: May 22, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (ACTUAL): June 14, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 14, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: smoking; vaping
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: IRB00047676; 1U54DA031659-01 (U.S. NIH Grant/Contract); U54DA031659-06 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be available to other researchers, please contact the principal investigator for instructions.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No