Tobacco Use DisorderPhase 2NCT04090879
Low Nicotine Content Cigarettes in Vulnerable Populations: Affective Disorders
A Phase 2 study testing Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g) and E-Cigarettes in people with Tobacco Use Disorder, run by Brown University at 2 sites in United States.
Trial summary
While the prevalence of smoking in the United States general population has declined over the past 50 years, there has been little to no decline among people with mental health conditions. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Use Disorder
- What is being tested?
- Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g) and E-Cigarettes
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 326 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Oct 2020to 27 Nov 2023
- Phase
- Phase 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Between 21 years and 70 years old
- Must have current diagnosis of an Affective Disorder.
Who cannot join
- Being without an Affective Disorder
- Younger than 21 years old
- Older than 70 years old
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Vermont
Burlington, Vermont, 05401
Brown University
Providence, Rhode Island, 02912
About this study
While the prevalence of smoking in the United States general population has declined over the past 50 years, there has been little to no decline among people with mental health conditions. Affective Disorders (ADs) are the most common mental health conditions in the US, and over 40% of people with ADs are current smokers. A national policy of reducing the nicotine content of cigarettes has the potential to reduce tobacco use, dependence, and related adverse health outcomes. Controlled trials in psychiatrically-stable smokers have shown that reducing the nicotine content in cigarettes can reduce cigarettes per day (CPD), dependence and tobacco toxicant exposure, with few adverse consequences.
The goal of the proposed trial is to experimentally model whether increasing the availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) moderates the effect of altering the nicotine in cigarettes in smokers with ADs. Additionally, investigators will test whether allowing participants to personalize the flavor of the e-liquid alters any moderating effects their availability may have on tobacco cigarette smoking.
Read more
Daily smokers with current ADs will be recruited at Brown University and the University of Vermont.
Investigators will study two research cigarettes referred to here as Research Cigarette 1 (RC1) and Research Cigarette 2 (RC2). One of these cigarettes will be a normal nicotine content cigarette and the other will be a reduced nicotine content cigarette. Investigators will study two e-cigarette conditions referred to here as E-Cigarette Condition 1 (EC1) and E-Cigarette Condition 2 (EC2). Both e-cigarette conditions will involve the same commercially available devices and same nicotine-containing e-liquid, but in one condition that e-liquid will be available only in tobacco flavor while in the other condition that e-liquid will be available in multiple flavors from which participants can choose based on personal taste preference. Participants will be assigned to one of the following four study conditions: (1) RC1 only; (2) RC2 only; (3) RC2 + EC1; (4) RC2 + EC2.
Participants will be asked to use only their assigned study products for 16 weeks. Outcome measures include total CPD, cigarette demand assessed by behavioral economics-based purchase tasks, craving, withdrawal, psychiatric symptoms, breath carbon monoxide (CO), biomarkers of tobacco toxicant exposure, brain function and structure, and airway inflammation (fractional nitric oxide concentration in exhaled breath [FeNO]).
- Conditions
- Tobacco Use Disorder
- Being tested
- Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g), E-Cigarettes
- Keywords
- Biomarkers of Exposure, Compensatory Smoking, Nicotine Dependence, Reduced Nicotine Cigarettes, Affective Disorders, Tobacco Withdrawal, Vulnerable Populations, E-Cigarettes
- Medical subject headings
- Tobacco Use Disorder, Mood Disorders, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)Other
- Altering the nicotine content of the tobacco research cigarette
E-CigarettesOther
- Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition
| Study group | Role | What they receive |
|---|---|---|
| RC 1 only | Experimental | Research Cigarettes #1 Receives: Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g) |
| RC 2 only | Experimental | Research Cigarettes #2 Receives: Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g) |
| RC 2 + EC 1 | Experimental | Research Cigarettes #2 plus E-cigarettes #1 (participants receive tobacco flavor only) Receives: Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g); Other: E-Cigarettes |
| RC 2 + EC 2 | Experimental | Research Cigarettes #2 plus E-cigarettes #2 (participants can choose among varying flavors) Receives: Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g); Other: E-Cigarettes |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cigarettes Per Day
Cigarettes per day will be assessed for use of cigarettes with different nicotine content.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2019
- Study start18 Oct 2020
- Primary completion27 Nov 2023
- Study completion27 Nov 2023
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Tobacco Use DisorderStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized parallel groups research design
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 326 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Food and Drug Administration (FDA), National Institute on Drug Abuse (NIDA), University of Vermont
- Responsible party
- Principal investigator, Jennifer Tidey, Brown University
- Investigators
- Jennifer W Tidey, Ph.D., Principal investigator, Brown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04090879
- Sponsor's protocol ID
- CHRMS19-0129
- Other IDs
- U54DA036114-06
- Status last verified
- Mar 2025
- First submitted
- 13 Sep 2019
- Last updated
- 1 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Nolder KA, Erath TG, DeSarno MJ, Klemperer EM, Higgins ST. A further examination of the validity of assessing demand intensity using the Cigarette Purchase Task. Exp Clin Psychopharmacol. 2026 Aug 6:10.1037/pha0000874. doi: 10.1037/pha0000874. Online ahead of print.
PubMed 42560883Higgins ST, Sigmon SC, Tidey JW, Heil SH, Gaalema DE, Lee DC, DeSarno MJ, Klemperer EM, Menson KE, Cioe PA, Plucinski S, Wiley RC, Orr E. Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials. JAMA Netw Open. 2024 Sep 3;7(9):e2431731. doi: 10.1001/jamanetworkopen.2024.31731.
PubMed 39240566
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Nicotine Content Cigarettes in Vulnerable Populations: Affective Disorders
- ClinicalTrials.gov ID
- NCT04090879
- Acronym / sponsor ID
- CHRMS19-0129
- Conditions
- Tobacco Use Disorder
- Keywords
- Biomarkers of Exposure, Compensatory Smoking, Nicotine Dependence, Reduced Nicotine Cigarettes, Affective Disorders, Tobacco Withdrawal, Vulnerable Populations, E-Cigarettes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 326 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Food and Drug Administration (FDA), National Institute on Drug Abuse (NIDA), University of Vermont
- Study start
- 18 Oct 2020 (actual)
- Primary completion
- 27 Nov 2023 (actual)
- Study completion
- 27 Nov 2023 (actual)
- First posted
- 16 Sep 2019 (actual)
- Results
- Posted 1 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
While the prevalence of smoking in the United States general population has declined over the past 50 years, there has been little to no decline among people with mental health conditions. Affective Disorders (ADs) are the most common mental health conditions in the US, and over 40% of people with ADs are current smokers. A national policy of reducing the nicotine content of cigarettes has the potential to reduce tobacco use, dependence, and related adverse health outcomes. Controlled trials in psychiatrically-stable smokers have shown that reducing the nicotine content in cigarettes can reduce cigarettes per day (CPD), dependence and tobacco toxicant exposure, with few adverse consequences.
The goal of the proposed trial is to experimentally model whether increasing the availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) moderates the effect of altering the nicotine in cigarettes in smokers with ADs. Additionally, investigators will test whether allowing participants to personalize the flavor of the e-liquid alters any moderating effects their availability may have on tobacco cigarette smoking.
Daily smokers with current ADs will be recruited at Brown University and the University of Vermont.
Investigators will study two research cigarettes referred to here as Research Cigarette 1 (RC1) and Research Cigarette 2 (RC2). One of these cigarettes will be a normal nicotine content cigarette and the other will be a reduced nicotine content cigarette. Investigators will study two e-cigarette conditions referred to here as E-Cigarette Condition 1 (EC1) and E-Cigarette Condition 2 (EC2). Both e-cigarette conditions will involve the same commercially available devices and same nicotine-containing e-liquid, but in one condition that e-liquid will be available only in tobacco flavor while in the other condition that e-liquid will be available in multiple flavors from which participants can choose based on personal taste preference. Participants will be assigned to one of the following four study conditions: (1) RC1 only; (2) RC2 only; (3) RC2 + EC1; (4) RC2 + EC2.
Participants will be asked to use only their assigned study products for 16 weeks. Outcome measures include total CPD, cigarette demand assessed by behavioral economics-based purchase tasks, craving, withdrawal, psychiatric symptoms, breath carbon monoxide (CO), biomarkers of tobacco toxicant exposure, brain function and structure, and airway inflammation (fractional nitric oxide concentration in exhaled breath [FeNO]).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomized parallel groups research design
| Arm | Type | Receives |
|---|---|---|
| RC 1 only | Experimental | Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)Research Cigarettes #1 |
| RC 2 only | Experimental | Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)Research Cigarettes #2 |
| RC 2 + EC 1 | Experimental | Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g), Other: E-CigarettesResearch Cigarettes #2 plus E-cigarettes #1 (participants receive tobacco flavor only) |
| RC 2 + EC 2 | Experimental | Other: Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g), Other: E-CigarettesResearch Cigarettes #2 plus E-cigarettes #2 (participants can choose among varying flavors) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Between 21 years and 70 years old
- Must have current diagnosis of an Affective Disorder.
Key exclusion criteria (3 listed)
- Being without an Affective Disorder
- Younger than 21 years old
- Older than 70 years old
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 |
|---|---|---|
| Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g)1) Altering the nicotine content of the tobacco research cigarette | Other | RC 1 only, RC 2 + EC 1, RC 2 + EC 2, RC 2 only |
| E-Cigarettes1) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition | Other | RC 2 + EC 1, RC 2 + EC 2 |
Primary outcome
Cigarettes Per Day
Time frame: 16 weeks
Cigarettes per day will be assessed for use of cigarettes with different nicotine content.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42560883Nolder KA, Erath TG, DeSarno MJ, Klemperer EM, Higgins ST. A further examination of the validity of assessing demand intensity using the Cigarette Purchase Task. Exp Clin Psychopharmacol. 2026 Aug 6:10.1037/pha0000874. doi: 10.1037/pha0000874. Online ahead of print.
- Derived from this study: PubMed 39240566Higgins ST, Sigmon SC, Tidey JW, Heil SH, Gaalema DE, Lee DC, DeSarno MJ, Klemperer EM, Menson KE, Cioe PA, Plucinski S, Wiley RC, Orr E. Reduced Nicotine Cigarettes and E-Cigarettes in High-Risk Populations: 3 Randomized Clinical Trials. JAMA Netw Open. 2024 Sep 3;7(9):e2431731. doi: 10.1001/jamanetworkopen.2024.31731.
- Individual participant dataSharing planned: Yes
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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.
Jennifer W Tidey, Ph.D. principal investigator
Brown University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Either normal nicotine content cigarettes (15.8mg/g) or reduced nicotine content cigarettes (0.4mg/g) and E-Cigarettes in people with Tobacco Use Disorder, run by Brown University at 2 sites 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 2 inclusion and 3 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 1 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 phase mean?
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 1 Apr 2025). 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?
Cigarettes Per Day (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04090879, which also lists 2 linked publications.
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 1 Apr 2025.