Impact of Nicotine Reduction on Adolescent Cigarette Use, Alternative Tobacco Use, and Harm From Tobacco

Study Overview
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Brief Summary
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Adolescents are an important vulnerable population to consider as the FDA moves toward a nicotine reduction policy. Such a policy, which would mandate a reduction of nicotine in all commercially available cigarettes, has the potential to transform public health and greatly reduce the toll of tobacco-related death and disease. Yet, data on the effects of such a policy on cigarette use among adolescents are lacking. Further, the advent of e-cigarettes and the popularity of alternative tobacco products have fundamentally altered the current landscape of nicotine delivery, and these products are widely used by adolescents. Although adolescent cigarette use is at an all-time low in the U.S., this reduction has been mirrored by an increase in e-cigarette use, and multiple tobacco product (MTP) use is the most common pattern of use in youth. Adolescent MTP users are more likely to be dependent on nicotine and to have begun using tobacco earlier than their single-product using peers. Thus, MTP-using youth differ from youth who solely smoke cigarettes in meaningful ways that have implications for responses to a nicotine reduction regulatory policy. In adults, longer-term studies have demonstrated that very low nicotine content (VLNC) cigarette exposure results in fewer cigarettes smoked and reduced toxicant exposure; however, increased use of alternative tobacco products has also been reported. No studies to date have examined the effects of VLNC cigarettes on MTP use or toxicant exposure in youth. This study will use real-time, smartphone-based ecological momentary assessment (EMA) and laboratory-based assessments to: (1) investigate the effects of cigarette nicotine reduction on cigarette and MTP use, (2) assess the influence of cigarette nicotine reduction on the harms associated with tobacco use, including nicotine and toxicant exposure, respiratory symptoms, perceived health risk and nicotine dependence, and (3) use a combination of laboratory and real-time assessment to investigate the effects of nicotine reduction on changes in withdrawal, craving, and the reinforcing efficacy of cigarettes to characterize the mechanisms by which VLNC use may affect behavior. Overall, this project will help determine the effects of VLNC cigarettes on real-world tobacco use behavior and indices of tobacco-related harm in adolescents, and examining the mechanisms through which nicotine reduction in cigarettes may effect such changes.

Official Title
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Impact of Nicotine Reduction on Adolescent Cigarette Use, Alternative Tobacco Use, and Harm From Tobacco

Conditions
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Nicotine Dependence, Cigarettes, Uncomplicated

Intervention / Treatment
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* Drug: Very Low Nicotine Content Cigarettes
* Drug: Normal Nicotine Content Cigarettes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Ages 15-20 inclusive 2) Male and female current daily smokers Defined as self-reported daily cigarette smoking at phone screening AND a breath carbon monoxide (CO) criterion of 5 ppm or higher; if this is not met, urine cotinine levels, detected by a NicAlert cotinine screening device, must indicate recent smoking (level 3 or higher) 3) Current users of alternative tobacco product(s) a. Defined as any self-reported use of at least one non-cigarette tobacco product (e.g., e-cigarettes, little cigars, cigarillos, hookah, etc.) in the past 30 days 4) Participants must speak and comprehend English well enough to complete study procedures. a. Participant will be asked to read aloud first few lines of informed consent and then summarize the contents aloud to check for competency 5) Participants under 18 must provide assent and parental consent from a parent/guardian. a. Participants age 18 or 19 may provide their own written consent contingent on photo ID verification of age. Exclusion Criteria: 1) Unwilling to use research cigarettes as part of the study 2) Self-reported daily drinking of alcohol or use of illicit or non-prescribed drugs (excluding marijuana) > 10 days in the past 30 days a. We will ask about daily alcohol and drug use in the phone screen, and we will use the Timeline Follow-Back to assess current and recent marijuana and alcohol use. 3) Currently seeking treatment to quit smoking, and/or intending to quit smoking for good in the next 30 days This information corresponds to questions 2 & 3 of the Stages of Change measure which will be administered at the in-person screening. These participants will be excluded, and provided with referral information for cessation services in the community. 4) Suicidal ideation in the past month or any past-year suicide attempts a. Suicidal ideation determined by the MINI ( Mini International Neuropsychiatric Interview) suicide subscale at the in-person screening (Questions 4 and 5) b. Suicide attempt in the past year determined by MINI question 6.a. (If participant has a lifetime history of suicide attempt between 1 and 10 years ago, licensed medical monitor approval required) c. If a participant indicates that he/she currently has suicidal ideation during this or any future session, the Emergency Protocol will be followed in which a Licensed Clinician will be contacted immediately, and participants will speak with the clinician over the phone and the clinician will determine the appropriate action to take to keep the child safe. 5) Pregnant or breastfeeding a. Determined by urine test at in-person screening; tested again at each in-person visit; participant will be excluded or withdrawn if test indicates pregnancy b. Self-reports current breastfeeding at in-person screening 6) Any medical or psychiatric conditions in which participation is likely to pose a significant threat to health or for which the condition could interfere with the ability of the participant to fully participate (as determined by LMP). 7) Having participated in another research study during the past year in which they were switched to research cigarettes for longer than one week.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Very Low Nicotine Content Cigarettes<br> | Drug: Very Low Nicotine Content Cigarettes<br>* Very Low Nicotine Content Cigarettes<br>|
| Active Comparator: Normal Nicotine Content Cigarettes<br> | Drug: Normal Nicotine Content Cigarettes<br>* Normal Nicotine Content Cigarettes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Cigarettes Smoked Per Day | Average number of cigarettes (study and non-study) smoked in the past week prior to the final session. | Week 4 | 
| Average Number of Days of Combustible and Noncombustible Use | Average number of days of combustible and noncombustible use. This measure is a sum of the days of combustible use (out of 7 days) and noncombustible use (out of 7 days) recorded in the week prior to week 4, averaged over 14 days. As this measure is a sum of the two variables, its possible range is 0-14. | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of Noncombustible Alternative Product Use | Number of days of noncombustible tobacco product use in the past 7 days prior to week 4 | Week 4 | 
| Average Study Cigarettes Per Day | Average number of study cigarettes smoked per day across 7 days prior to week 4 | Week 4 | 
| Toxicant Exposure | Total Nicotine Equivalents (TNEs) | Week 4 |