Evaluating New Nicotine Standards for Cigarettes - Project 3 (CENIC2-P3)

Effects of Very Low Nicotine Content Cigarettes and E-cigarette Characteristics on Smoking in Adolescents

This study is designed to examine how the nicotine content of cigarettes and the nicotine concentration and flavors in e-liquids influence responses to and use of these products in adolescent smokers. Participants will complete a total of six sessions (an in-person screening/baseline session and five lab sessions.

Study Overview

• Status: Completed
• Conditions: Smoking, Cigarette; Electronic Cigarettes
• Intervention / Treatment: Behavioral: Spectrum Research Cigarettes

Detailed Description

Adolescence is a critical developmental period for tobacco initiation and progression to regular use and dependence. The Food and Drug Administration (FDA) has the authority to establish standards for tobacco products for the protection of public health, including the authority to mandate a reduction in the nicotine content of all cigarettes to minimally addictive levels. Numerous studies have found that adult smokers who are switched to very low nicotine content (VLNC) cigarettes experience reductions in smoking rates, nicotine intake, nicotine dependence and abstinence-induced craving relative to those who use normal nicotine content (NNC) cigarettes. However, studies of VLNC cigarettes in adolescent smokers are limited and more information is needed to inform potential product standards. Furthermore, use of electronic nicotine delivery systems (ENDS), e-cigarettes or vaping devices, has increased dramatically in adolescents. Therefore, effects of VLNC cigarettes on smoking in youth should be examined in the context of vaping device availability. This study is designed to examine how the nicotine content of cigarettes and the nicotine concentration and flavors in e-liquids influence responses to these products in adolescents.

Participants will complete an in-person baseline session in which eligibility criteria are confirmed and background questionnaires are completed. Next, participants will complete five in-person lab sessions in which NNC or VLNC cigarettes are available (based on random assignment). During the first lab session, participants will test the assigned research cigarettes when no alternative product is available. During each of the four remaining lab sessions, smokers' responses to the assigned research cigarettes will be compared to their responses to a vaping device with the following characteristics: 1) no nicotine, tobacco flavor; 2) no nicotine, non-tobacco flavor; 3) moderate nicotine concentration, tobacco flavor; or 4) moderate nicotine concentration, non-tobacco flavor. In each session, after sampling and rating the subjective effects of the products available during that session, participants will make a series of 10 choices. Choices will be for either 2 puffs of the research cigarette, 2 puffs of the vaping device, or abstinence from puffing.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Brown University School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Ages 15-20
2. Adolescents who report current daily or near daily cigarette smoking for at least 3 months
3. Must have used an electronic nicotine device on a minimum of two lifetime occasions.
4. Breath Carbon Monoxide (CO) levels > 5 ppm (if < 5 ppm, then cotinine assay via NicAlert Strip = > 3)
5. Speak, comprehend, and read English well enough to complete study procedures

Exclusion Criteria:

1. Unwilling to use research cigarettes or ENDS as part of the study
2. Intention to quit smoking in the next 30 days
3. Using tobacco products (other than ENDS or roll-your-own tobacco) > 15 days in the past 30 days.
4. Any medical or psychiatric condition in which participation is likely to post a significant threat to health or for which the condition could interfere with the ability of the participant to fully participants (as determined by the LMP)
5. Self-reported illicit use of any drug except marijuana > 10 days in the past 30 days
6. Binge drinking alcohol (>10 days in the past 30 days, >4/5 drinks in a 2-hour period (female/male))
7. Pregnant or breastfeeding
8. CO reading > 80 ppm
9. Systolic BP outside the range of 90-159, diastolic BP outside the range of 50-99, or heart rate outside the range of 45-104. Participants failing for any of these criteria will be allowed to re-screen once per criterion.
10. Indicating Yes on Questions 4-6 on the MINI with a suicide attempt in the past 2 years (if within the past 2-10 years, LMP approval required).
11. Having participated in another research study during the past year in which they were switched to reduced nicotine cigarettes for longer than one week.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Normal Nicotine Content Cigarettes; Spectrum Research Cigarettes: 15.8 mg nicotine/g tobacco, 9 mg of tar	Behavioral: Spectrum Research Cigarettes; Participants will be assigned to either normal nicotine content cigarettes or very low nicotine content cigarettes.
Experimental: Very Low Nicotine Content Cigarettes; Spectrum Research Cigarettes: 0.4 mg nicotine/g tobacco, 9 mg of tar	Behavioral: Spectrum Research Cigarettes; Participants will be assigned to either normal nicotine content cigarettes or very low nicotine content cigarettes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Cigarette Puffs Taken (0 to 20)	The number of cigarette puffs selected during a 30 minute choice procedure when no vaping device was available	30-minute preference task
Number of Cigarette Puffs Taken (0 to 20) When the Available Vaping Device Has 3mg/ml of Nicotine and Was Available in Tobacco Flavor	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device has 3mg/ml of nicotine and was available in tobacco flavor	30-minute preference task
Number of Cigarette Puffs Taken (0 to 20) When the Available Vaping Device Has 3mg/ml of Nicotine and Was Available in Non-tobacco Flavors	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device has 3mg/ml of nicotine and was available in non-tobacco flavors	30-minute preference task
Number of Cigarette Puffs Taken (0 to 20) When the Available Vaping Device Has 18mg/ml of Nicotine and Was Available in Tobacco Flavor	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device has 18mg/ml of nicotine and was available in tobacco flavor	30-minute preference task
Number of Cigarette Puffs Taken (0 to 20) When the Available Vaping Device Has 18mg/ml of Nicotine and Was Available in Non-tobacco Flavors	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device has 18mg/ml of nicotine and was available in non-tobacco flavors	30-minute preference task

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of E-cig Puffs Taken (0 to 20) When the Available Vaping Device Contained 3mg/ml Nicotine and Was Available in Tobacco Flavor	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device contained 3mg/ml nicotine and was available in tobacco flavor	30-minute preference task session
Number of E-cig Puffs Taken (0 to 20) When the Available Vaping Device Contained 3mg/ml Nicotine and Was Available in Non-tobacco Flavors	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device contained 3mg/ml nicotine and was available in non-tobacco flavors	30-minute preference task session
Number of E-cig Puffs Taken (0 to 20) When the Available Vaping Device Contained 18mg/ml Nicotine and Was Available in Tobacco Flavor	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device contained 18mg/ml nicotine and was available in tobacco flavor	30-minute preference task session
Number of E-cig Puffs Taken (0 to 20) When the Available Vaping Device Contained 18mg/ml Nicotine and Was Available in Non-tobacco Flavors	The number of cigarette puffs selected during a 30 minute choice procedure when the available vaping device contained 18mg/ml nicotine and was available in non-tobacco flavors	30-minute preference task session
Carbon Monoxide Change From pre-to the Post-choice Task When no Vaping Device Was Available	Post-choice CO minus pre-choice CO at session 1 in which no vaping device was available	30-minute preference task
Carbon Monoxide Change From pre-to the Post-choice Task When the Available Vaping Device Contained 3mg/ml Nicotine and Was Available in Tobacco Flavor	Post-choice CO minus pre-choice CO when the available vaping device contained 3mg/ml nicotine and was available in tobacco flavor	30-minute preference task
Carbon Monoxide Change From pre-to the Post-choice Taskwhen the Available Vaping Device Contained 3mg/ml Nicotine and Was Available in Non-tobacco Flavors	Post-choice CO minus pre-choice CO when the available vaping device contained 3mg/ml nicotine and was available in non-tobacco flavors	30-minute preference task
Carbon Monoxide Change From pre-to the Post-choice Task When the Available Vaping Device Contained 18mg/ml Nicotine and Was Available in Tobacco Flavor	Post-choice CO minus pre-choice CO when the available vaping device contained 18mg/ml nicotine and was available in tobacco flavor	30-minute preference task
Carbon Monoxide Change From pre-to the Post-choice Task When the Available Vaping Device Contained 18mg/ml Nicotine and Was Available in Non-tobacco Flavors	Post-choice CO minus pre-choice CO when the available vaping device contained 18mg/ml nicotine and was available in non-tobacco flavors	30-minute preference task

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minnesota Nicotine Withdrawal Scale (MNWS)	Measures withdrawal symptoms	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Questionnaire of Smoking Urges (QSU)	Measures craving	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Positive and Negative Affect Scale (PANAS)	Measures positive and negative affect	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Cigarette Evaluation Scale (CES)	Measures subjective responses cigarettes	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Cigarette Purchase Task	Measures demand for cigarettes across a range of prices	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Perceived Health Risk Scale	Measures perceived risk of cigarettes	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Total Nicotine Equivalents (TNE)	Biomarkers	Baseline; Week 1
Nicotine Metabolite Ratio (NMR)	Biomarkers	Baseline; Week 1
Cotinine	Biomarkers: measures a metabolite of nicotine	Baseline; Week 1
Carbon Monoxide (CO)	Biomarkers: measures expired alveolar carbon monoxide level	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Number of Choices for Cigarette Puffs	0 to 10	30-minute preference task at each of the 5 laboratory sessions
Number of Choices for E-cig Puffs	0 to 10	30-minute preference task at each of the 5 laboratory sessions
Number of Choices to Abstain From Puffing	0 to 10	30-minute preference task at each of the 5 laboratory sessions
Drop-out Rate	Measures of compliance	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Heart Rate	Measures of cardiovascular function	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks
Blood Pressure	Measures of cardiovascular function	Baseline-Lab Session 5; 2-8 weeks; average 3-4 weeks

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: National Institute on Drug Abuse (NIDA); University of Minnesota; Food and Drug Administration (FDA); Wake Forest University
• Investigators: Principal Investigator: Suzanne Colby, PhD, Brown University; Principal Investigator: Jennifer Tidey, PhD, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 19, 2017
• First Posted (Actual): June 21, 2017

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Smoking; Cigarettes; E-Cigarettes
• Other Study ID Numbers: 1705001771; U54DA031659 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Intend to share findings from this research through publications and presentations. Institutions and individuals wishing to access any resources or data must contact the Principal Investigator (Hatsukami). Data will be available in two formats. One will be a summary of the data, with graphs and tables, posted as pdf files and as raw individual-level data for analysis. Data generated by this grant will be made to outside investigators, according to NIH Guidance. When data are shared, there will be no limits placed on how the data will be used. Users will agree, however, that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. A record of transfer of data and a copy of the dataset that was distributed will be kept by Brown University.
• IPD Sharing Time Frame: Data will not be available until primary and secondary papers are accepted for publication.
• IPD Sharing Access Criteria: Persons requesting data must do so in writing, identifying their affiliation and how the data will be used. Upon review, access will be determined.

Drug and device information, study documents

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