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

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.

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence, Cigarettes, Uncomplicated
• Intervention / Treatment: Drug: Very Low Nicotine Content Cigarettes; Drug: Normal Nicotine Content Cigarettes

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2; Phase 1

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 19 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1) Ages 15-20 inclusive 2) Male and female current daily smokers

  1. Defined as self-reported daily cigarette smoking at phone screening AND
  2. 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

  1. This information corresponds to questions 2 & 3 of the Stages of Change measure which will be administered at the in-person screening.

  2. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Very Low Nicotine Content Cigarettes	Drug: Very Low Nicotine Content Cigarettes; Very Low Nicotine Content Cigarettes
Active Comparator: Normal Nicotine Content Cigarettes	Drug: Normal Nicotine Content Cigarettes; Normal Nicotine Content Cigarettes

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
American Thoracic Society Questionnaire	Respiratory Health Symptoms; an 8-item questionnaire measuring frequency of experience respiratory symptoms; scores can range from 8 to 40 and greater scores indicate greater frequency.	Baseline-Week 4
Craving	Questionnaire on Smoking Urges (QSU) post- smoking in the laboratory, a 10 item scale that is comprised of 2 factors; Factor 1 included items 1, 3, 6, 7, and 10 Factor 2 included items 2, 4, 5, 8, and 9 The score for each factor is calculated by summing the item scores; the total score is calculated by summing all 10 items. A single-item craving question (ranging from 1-10, not all to greatly) from daily random and post-event Ecological Momentary Assessments.	Baseline-Week 4
Withdrawal	Minnesota Nicotine Withdrawal Scale 7-item version; greater score indicates greater withdrawal	Baseline-Week 4
Subjective Response to Cigarettes	Cigarette Evaluation Scale post-smoking in the laboratory; 5 subscales are derived from this scale: Psychological Reward, Smoking Satisfaction, Enjoyment of Respiratory Sensations, Craving Reduction; Aversion. Event level on satisfaction derived from post-use responses on daily Ecological Momentary Assessments.	Baseline-Week 4
Hypothetical Purchasing of Cigarettes	Cigarette Purchase Task; Five indices of demand for cigarettes are derived from this measure (Intensity, Omax, Breakpoint, Pmax, Alpha)	Baseline-Week 4
Hypothetical Purchasing of Tobacco Products	Purchasing of cigarettes and other tobacco products across changing prices in Experimental Tobacco Marketplace task	Baseline-Week 4
Perceived Health Risk Questionnaire	Perceived risk for developing diseases associated with use study cigarettes and usual brand cigarettes; Scores range from 1 (much less risk) to 5 (much greater risk) for each disease	Week 4
Nicotine Dependence	Modified Fagerstrom Tolerance Questionnaire (mFTQ) score; Scale 2-8, higher scores indicate greater nicotine dependence	Baseline-Week 4

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Rachel Cassidy, PhD, Brown University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2019
• Primary Completion (Actual): March 23, 2022
• Study Completion (Actual): March 23, 2022

Study Registration Dates

• First Submitted: February 15, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; 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: R01DA047356 (U.S. NIH Grant/Contract); 1R01DA047356-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The investigators involved in this project intend to share findings from its research through publications and presentations. After all data have been collected and the results of the study have been published, de-identified data will be made available to other qualified investigators upon request. Institutions and/or individuals wishing to access any resources or data must contact the Principal Investigators. Persons requesting data must do so in writing, identifying their affiliation and how and by whom the data will be used. The request will be evaluated by the PIs and Co-Investigators to ensure that it meets reasonable demands of scientific integrity.

Drug and device information, study documents

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