Nicotine Dependence, Cigarettes, UncomplicatedPhase 1/2SIRENNCT03860077
Impact of Nicotine Reduction on Adolescent Cigarette Use, Alternative Tobacco Use, and Harm From Tobacco
A Phase 1/2 study testing Very Low Nicotine Content Cigarettes and Normal Nicotine Content Cigarettes in people with Nicotine Dependence, Cigarettes, Uncomplicated, run by Brown University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 15 to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Nicotine Dependence, Cigarettes, Uncomplicated
- What is being tested?
- Very Low Nicotine Content Cigarettes and Normal Nicotine Content Cigarettes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2019to 23 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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)
- 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.
- 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.
- Participants age 18 or 19 may provide their own written consent contingent on photo ID verification of age.
Who cannot join
- 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
- 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
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- 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
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brown University School of Public Health
Providence, Rhode Island, 02912
About this study
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.
- Being tested
- Very Low Nicotine Content Cigarettes, Normal Nicotine Content Cigarettes
- Medical subject headings
- Tobacco Use Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Very Low Nicotine Content CigarettesDrug
Very Low Nicotine Content Cigarettes
Normal Nicotine Content CigarettesDrug
Normal Nicotine Content Cigarettes
| Study group | Role | What they receive |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Experimental | Not described Receives: Drug: Very Low Nicotine Content Cigarettes |
| Normal Nicotine Content Cigarettes | Active comparator | Not described Receives: Drug: Normal Nicotine Content Cigarettes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Cigarettes Smoked Per Day
Average number of cigarettes (study and non-study) smoked in the past week prior to the final session.
Measured: 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.
Measured: Week 4
Secondary outcomes (3)
Amount of Noncombustible Alternative Product Use
Number of days of noncombustible tobacco product use in the past 7 days prior to week 4
Measured: Week 4
Average Study Cigarettes Per Day
Average number of study cigarettes smoked per day across 7 days prior to week 4
Measured: Week 4
Toxicant Exposure
Total Nicotine Equivalents (TNEs)
Measured: Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start10 Oct 2019
- Primary completion23 Mar 2022
- Study completion23 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Nicotine Dependence, Cigarettes, UncomplicatedStudies of the same condition, open and under way.
- More trials run by Brown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Rachel Cassidy, PhD, Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03860077
- Sponsor's protocol ID
- R01DA047356
- Other IDs
- 1R01DA047356-01
- Acronym
- SIREN
- Status last verified
- Dec 2023
- First submitted
- 15 Feb 2019
- Last updated
- 19 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Nicotine Reduction on Adolescent Cigarette Use, Alternative Tobacco Use, and Harm From Tobacco
- ClinicalTrials.gov ID
- NCT03860077
- Acronym / sponsor ID
- SIREN / R01DA047356
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 10 Oct 2019 (actual)
- Primary completion
- 23 Mar 2022 (actual)
- Study completion
- 23 Mar 2022 (actual)
- First posted
- 1 Mar 2019 (actual)
- Results
- Posted 19 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Experimental | Drug: Very Low Nicotine Content Cigarettes |
| Normal Nicotine Content Cigarettes | Active comparator | Drug: Normal Nicotine Content Cigarettes |
Who may qualify
- Ages
- 15 to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 1) Ages 15-20 inclusive 2) Male and female current daily smokers
Key exclusion criteria (10 listed)
- 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
- 3) Currently seeking treatment to quit smoking, and/or intending to quit smoking for good in the next 30 days
- 4) Suicidal ideation in the past month or any past-year suicide attempts
- 5) Pregnant or breastfeeding
- 7) Having participated in another research study during the past year in which they were switched to research cigarettes for longer than one week.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Very Low Nicotine Content CigarettesVery Low Nicotine Content Cigarettes | Drug | Very Low Nicotine Content Cigarettes |
| Normal Nicotine Content CigarettesNormal Nicotine Content Cigarettes | Drug | Normal Nicotine Content Cigarettes |
Primary outcome
Average Cigarettes Smoked Per Day
Time frame: Week 4
Average number of cigarettes (study and non-study) smoked in the past week prior to the final session.
Average Number of Days of Combustible and Noncombustible Use
Time frame: Week 4
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.
3 secondary outcomes
Amount of Noncombustible Alternative Product Use
Time frame: Week 4
Average Study Cigarettes Per Day
Time frame: Week 4
Toxicant Exposure
Time frame: Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Cassidy, PhD principal investigator
Brown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Very Low Nicotine Content Cigarettes and Normal Nicotine Content Cigarettes in people with Nicotine Dependence, Cigarettes, Uncomplicated, run by Brown University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Average Cigarettes Smoked Per Day (time frame: Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023; AzTrials last refreshed its copy on 8 Nov 2026.