Evaluating New Nicotine Standards for Cigarettes - Project 3

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03194256

Acronym

CENIC2-P3

Enrollment

Registered

2017-06-21

Start date

2018-09-01

Completion date

2022-11-30

Last updated

2023-12-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Electronic Cigarettes, Smoking, Cigarette

Keywords

Smoking, Cigarettes, E-Cigarettes

Brief summary

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.

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.

Interventions

BEHAVIORALSpectrum Research Cigarettes

Participants will be assigned to either normal nicotine content cigarettes or very low nicotine content cigarettes.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Masking description

Participants will be blind to the nicotine content of their assigned study cigarette and the nicotine dose of the e-liquid in the study vaping device. Investigators, research staff, and biostatisticians will also be blind to the conditions. E-liquid flavors will not be blinded.

Intervention model description

Mixed between subjects and within-subjects design. Random assignment to the between subjects factor (nicotine content in cigarettes), within-subjects manipulation of nicotine concentration and flavors in e-liquid in the electronic cigarettes

Eligibility

Sex/Gender

ALL

Age

15 Years to 20 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

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

Secondary

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

Other

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
Normal Nicotine Content Cigarettes Spectrum Research Cigarettes: 15.8 mg nicotine/g tobacco, 9 mg of tar Spectrum Research Cigarettes: Participants will be assigned to either normal nicotine content cigarettes or very low nicotine content cigarettes.	41
Very Low Nicotine Content Cigarettes Spectrum Research Cigarettes: 0.4 mg nicotine/g tobacco, 9 mg of tar Spectrum Research Cigarettes: Participants will be assigned to either normal nicotine content cigarettes or very low nicotine content cigarettes.	39
Total	80

Baseline characteristics

Characteristic	Very Low Nicotine Content Cigarettes	Total	Normal Nicotine Content Cigarettes
Age, Continuous	18.7 years STANDARD_DEVIATION 0.8	18.8 years STANDARD_DEVIATION 0.8	18.9 years STANDARD_DEVIATION 0.7
Average Cigarettes Per Day	4.7 Cigarettes smoked per day STANDARD_DEVIATION 3.6	5.3 Cigarettes smoked per day STANDARD_DEVIATION 4.7	5.8 Cigarettes smoked per day STANDARD_DEVIATION 5.6
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	12 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants	66 Participants	32 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	2 Participants	2 Participants
Fagerstom Test for Nicotine Dependence	2.2 units on a scale STANDARD_DEVIATION 1.7	2.4 units on a scale STANDARD_DEVIATION 2	2.6 units on a scale STANDARD_DEVIATION 2.2
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	8 Participants	12 Participants	4 Participants
Race (NIH/OMB) Black or African American	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) More than one race	5 Participants	13 Participants	8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	2 Participants	0 Participants
Race (NIH/OMB) White	24 Participants	51 Participants	27 Participants
Region of Enrollment United States	39 participants	80 participants	41 participants
Sex/Gender, Customized Different identity	1 Participants	1 Participants	0 Participants
Sex/Gender, Customized Female	15 Participants	28 Participants	13 Participants
Sex/Gender, Customized Genderqueer/gender non-conforming	0 Participants	2 Participants	2 Participants
Sex/Gender, Customized Male	22 Participants	46 Participants	24 Participants
Sex/Gender, Customized Prefer not to answer	0 Participants	1 Participants	1 Participants
Sex/Gender, Customized Transgender female to male	0 Participants	0 Participants	0 Participants
Sex/Gender, Customized Transgender male to female	1 Participants	2 Participants	1 Participants
Sex/Gender, Customized Unknown	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 41	0 / 39
other Total, other adverse events	0 / 41	0 / 39
serious Total, serious adverse events	0 / 41	0 / 39

Outcome results

Primary

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