Cigarette and E-cigarette Nicotine Content in an Electronic Tobacco Marketplace (ETM)

The Impact of Cigarette Nicotine Content, E-Cigarette Nicotine Content and E-Cigarette Flavoring on Smoking Behavior in an Electronic Tobacco Marketplace

This study is proposing a four condition Electronic Tobacco Marketplace (ETM) study to determine if banning normal nicotine content (NNC) is sufficient for encouraging smokers to switch to potentially less harmful products or if the availability of higher nicotine and/or flavored alternative products (specifically e-cigarettes) are needed to achieve maximal reductions in smoking.

Study Overview

• Status: Completed
• Conditions: Tobacco Use
• Intervention / Treatment: Other: Normal Nicotine Content Vape with all flavor e-liquids; Other: Normal nicotine content vape with tobacco e-liquids; Other: Low nicotine content vape with all flavor e-liquids; Other: Low nicotine content vape with tobacco e-liquids

Detailed Description

The Family Smoking Prevention and Tobacco Control Act (FSPTCA) passed in 2009 provides the FDA with the authority to regulate tobacco products. One provision in this legislative act empowers the FDA to set limits on constituents in tobacco products, including nicotine. Such a measure has the potential to reduce the chance of individuals experimenting with smoking from becoming dependent and enable current smokers to quit when they are motivated to do so. Although the proposal to reduce nicotine in cigarettes has been met with skepticism by some because of concerns over compensatory smoking behavior and the potential emergence of a black market, this policy measure was considered to be technically feasible by the American Medical Association and the British Medical, by tobacco control researchers, policymakers and governmental officials who were convened in a meeting on nicotine regulation8, and by the World Health Organization Study Group on Tobacco Product Regulation. Most importantly, in July 2017, FDA Commissioner Gottlieb announced he was "directing our Center for Tobacco Products to develop a comprehensive nicotine regulatory plan premised on the need to confront and alter cigarette addiction." This announcement was followed on March 16, 2018 by the release of the Advance Notice of Proposed Rulemaking entitled "Tobacco Product Standard for Nicotine Level of Combusted Cigarettes" (ID: FDA-2017-N-6189-0001) "to obtain information for consideration in developing a tobacco product standard to set the maximum nicotine level for cigarettes."

This study proposes to conduct a within-subjects, multi-session virtual lab study and validation field assessment to determine how the availability of flavored e-liquids affects product purchasing among cigarette smokers. Adult daily cigarette smokers (N=64) will be recruited for this study. After initial eligibility is assessed, participants will complete six virtual sessions (1 baseline, 4 experimental, and 1 follow-up) and one field assessment to evaluate their tobacco use.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 21+ years of age
• Self-report smoking at least 5 cigarettes per day for the past year
• Breathe carbon monoxide (CO) level > 8 ppm or positive urine NicCheck
• Willingness to use other tobacco products during the study
• Speak, comprehend, and read English sufficiently to complete study procedures
• Have home access to a computer, smart phone, or tablet with a web camera and internet access
• Tried a vaping device at least once in their lifetime

Exclusion Criteria:

• Currently seeking treatment to quit smoking
• Self-reported serious medical or psychiatric condition(s) including cardiovascular and chronic respiratory diseases
• Body temperature > 100.4 F
• Cold, flu or COVID-19 symptoms including fever, cough, and runny nose in the past 30 days
• Currently pregnant, breastfeeding or intending to become pregnant for the duration of the study or unwilling to agree to use adequate protection to avoid pregnancy
• CO reading > 80 ppm

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Nicotine Content Vape with all flavor e-liquids	Other: Normal Nicotine Content Vape with all flavor e-liquids; Participants are randomly assigned to the order of each marketplace Group
Experimental: Normal nicotine content vape with tobacco e-liquids	Other: Normal nicotine content vape with tobacco e-liquids; Participants are randomly assigned to the order of each marketplace Group
Experimental: Low nicotine content vape with all flavor e-liquids	Other: Low nicotine content vape with all flavor e-liquids; Participants are randomly assigned to the order of each marketplace Group
Experimental: Low nicotine content vape with tobacco e-liquids	Other: Low nicotine content vape with tobacco e-liquids; Participants are randomly assigned to the order of each marketplace Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Cigarettes Purchased	Average number of cigarettes purchased (analyzed as raw data and using derived behavioral economic measures)	Visit 6 approximately 4 weeks after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of E-liquid Milliliters Purchased	Average number of e-liquid milliliters purchased (analyzed as raw data and using derived behavioral economic measures)	Visit 6 approximately 4 weeks after baseline
Proportion of Participants Completing Flavor and Nicotine Content Discrete Choice Projections	The proportion of participants projected to choose a cigarette over an e-cigarette under different potential regulatory scenarios, as determined by regression analysis.	Month 1 after baseline
Lung Cancer Perceived Risk Scores for VLNC Cigarettes	The response options rely on a 10-point Likert-like scale: 1 = very low risk of disease; 2, 3, 4, 5, 6, 7, 8, 9, 10 = very high risk of disease. Minimum possible response 1. Maximum possible response 10. The higher the score, the greater perceived risk of VLNC cigarettes for lung cancer.	Baseline
Product Evaluation Scale Scores	Product evaluation scale scores for VLNC cigarettes among participants who received VLNC cigarettes will be determined by a product evaluation questionnaire. The questionnaire measures the strength of self-reported positive subjective effects (e.g., reward, satisfaction) following product use. The response options rely on a 7-point Likert-like scale: 1=not at all; 2= very little; 3= a little; 4= moderately; 5= a lot; 6= quite a lot; 7= extremely. The summed score adds responses to 13 separate items. Minimum possible response: 13. Maximum possible response: 91. Higher scores denote more favorable product effects. Note: This was only administered (at Virtual Visit 6) to participants who received each product type in the field (dependent on their baseline ETM shopping trip purchases).	Visit 6 approximately 4 weeks after baseline
Minnesota Nicotine Withdrawal Scale Scores	Minnesota Nicotine Withdrawal Scale measures the severity of nicotine withdrawal symptoms. The response options rely on a 5-point Likert-like scale; 0=None; 1= Slight; 2=Mild; 3=Moderate; 4=Severe. There are 7 items total, that are summed. Minimum possible response: 0. Maximum possible response: 28. Higher scores denote greater severity of withdrawal symptoms.	Visit 6 approximately 4 weeks after baseline
Questionnaire on Smoking Urges Score	Questionnaire on Smoking Urges measures the strength of urges to smoke. The response options rely on a 7-point Likert-like scale: 1=Strongly Disagree; 2; 3; 4; 5; 6; 7= Strongly Agree. The questionnaire has 10 total items; scores sum responses to each item. Minimum possible response: 10. Maximum possible response: 70. Higher scores denote greater urges to smoke.	Visit 6 approximately 4 weeks after baseline
Tobacco Product Interest Scores	Tobacco Product Interest of different products; Slider scale ranging from 0=No Interest to 100=Very Interested	1 month after baseline
Tobacco Policy Questionnaire Scores	Tobacco Policy Questionnaire scored from Support, Oppose, and Don't know for personal opinions on Making Cigarettes Less Addictive	1 month after baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Product Use Themes Emerging From the Qualitative Interviews	Participants are asked about their opinions and experiences using tobacco products other than their usual brand during the field assessment.	Screening visit through end of study (up to week eight)
Tobacco Product Use During Field Assessment	Participants are asked what products they had used and quantity every day during the field assessment.	Screening visit through end of study (up to week eight)
Biomarkers of Exposure During Field Assessment - Carbon Monoxide	Product use and biomarkers of exposure during the field assessment will be analyzed using linear regression or other appropriate regression models. The model for primary analysis of these data will include main effects for each of the two factors (for the ETM condition carried into the field assessment), and the corresponding baseline measure to improve precision. Carbon Monoxide (CO) is collected in ppm.	Screening visit through end of study (up to week eight)
Biomarkers of Exposure During Field Assessment - Cotinine	Product use and biomarkers of exposure during the field assessment will be analyzed using linear regression or other appropriate regression models. The model for primary analysis of these data will include main effects for each of the two factors (for the ETM condition carried into the field assessment), and the corresponding baseline measure to improve precision. Cotinine is collected in ng/ml.	Screening visit through end of study (up to week eight)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Jarvis MJ, Bates C. Eliminating nicotine in cigarettes. Tob Control. 1999 Spring;8(1):106-7; author reply 107-9. No abstract available.
• Kozlowski LT. Prospects for a nicotine-reduction strategy in the cigarette endgame: Alternative tobacco harm reduction scenarios. Int J Drug Policy. 2015 Jun;26(6):543-7. doi: 10.1016/j.drugpo.2015.02.001. Epub 2015 Feb 23.
• Kozlowski LT. Cigarette prohibition and the need for more prior testing of the WHO TobReg's global nicotine-reduction strategy. Tob Control. 2017 Mar;26(e1):e31-e34. doi: 10.1136/tobaccocontrol-2016-052995. Epub 2016 Jun 29. No abstract available.
• Kozlowski LT. Let actual markets help assess the worth of optional very-low-nicotine cigarettes before deciding on mandatory regulations. Addiction. 2017 Jan;112(1):3-5. doi: 10.1111/add.13515. Epub 2016 Aug 23. No abstract available.
• Shatenstein S. Eliminating nicotine in cigarettes. Tob Control. 1999 Spring;8(1):106; author reply 107-9. No abstract available.
• Henningfield JE, Benowitz NL, Slade J, Houston TP, Davis RM, Deitchman SD. Reducing the addictiveness of cigarettes. Council on Scientific Affairs, American Medical Association. Tob Control. 1998 Autumn;7(3):281-93. doi: 10.1136/tc.7.3.281.
• Hatsukami DK, Perkins KA, Lesage MG, Ashley DL, Henningfield JE, Benowitz NL, Backinger CL, Zeller M. Nicotine reduction revisited: science and future directions. Tob Control. 2010 Oct;19(5):e1-10. doi: 10.1136/tc.2009.035584.
• World Health Organization. WHO STUDY GROUP ON TOBACCO PRODUCT REGULATION. Report on the Scientific Basis of Tobacco Product Regulations: Fifth Report of a WHO Study Group. World Health Organ Tech Rep Ser. 2015;(989):1-234, back cover.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): August 6, 2023

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: April 8, 2022
• First Posted (Actual): April 11, 2022

Study Record Updates

• Last Update Posted (Estimated): October 9, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Cigarette smoking
• 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: IRB00080010; 5U54DA031659-09 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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