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Tobacco Use DisorderPhase 2NCT04092101

Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder

A Phase 2 study testing Cigarettes with varying nicotine content and E-Cigarettes in people with Tobacco Use Disorder, run by University of Vermont at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Prevalence of smoking among individuals with opioid use disorder (OUD) is six-fold that of the general US adult population. The mortality rate of opioid-dependent smokers is four times that of opioid-dependent nonsmokers, and their response to smoking cessation interventions is notoriously poor. Read more about this study

Who is it for?
Ages 21 to 70 yearsHealthy volunteers can take part
Conditions the study is for
Tobacco Use Disorder
What is being tested?
Cigarettes with varying nicotine content 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 21 to 70 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Maintained on opioid medication
  • 21 to 70 years old

Who cannot join

  • Not maintained on opioid medication
  • Under 21 years old
  • Over 70 years old

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Shirley Plucinski

    Burlington, Vermont, 05401

Other trials in United States

About this study

Prevalence of smoking among individuals with opioid use disorder (OUD) is six-fold that of the general US adult population. The mortality rate of opioid-dependent smokers is four times that of opioid-dependent nonsmokers, and their response to smoking cessation interventions is notoriously poor. A national policy of reducing the nicotine content of cigarettes has the potential to be an effective method of reducing tobacco use prevalence, dependence, and related adverse health outcomes. Controlled trials in the general smoker population have demonstrated that switching smokers to low nicotine content cigarettes results in reductions in cigarettes per day (CPD), dependence and tobacco toxicant exposure, with few adverse consequences. The investigators believe that the impact of reduced nicotine standards on use of combusted cigarettes in this population will be moderated considerably by other tobacco market conditions including (1) availability of alternative sources of non-combusted nicotine, and (2) whether these alternatives are available under conditions that optimize their appeal. The investigators hypothesize the same for other vulnerable populations as well, but achieving significant reductions in use of combusted cigarettes in smokers with OUD seems especially unlikely in the absence of readily available and appealing alternative sources of non-combusted nicotine.

The goal of the proposed trial is to experimentally model whether increased availability and appeal of an alternative, non-combusted source of nicotine (e-cigarettes) will enhance the effectiveness of a reduced nicotine standard for cigarettes in smokers with OUD. Additionally, the investigators will test whether allowing participants to personalize the favor of the e-liquid alters any moderating effects their availability may have on tobacco cigarette smoking.

Read more

Daily smokers who are receiving methadone or buprenorphine treatment will be recruited at University of Vermont and Johns Hopkins University.

The investigators will study two research cigarettes referred to here as RC1 and 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 EC1 and 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), and biomarkers of tobacco toxicant exposure.

Being tested
Cigarettes with varying nicotine content, 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.

  • Cigarettes with varying nicotine contentOther

    1. Altering the nicotine content of the tobacco research cigarette
  • E-CigarettesOther

    1. Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition
Study groups in NCT04092101
Study groupRoleWhat they receive
RC 1 onlyExperimentalResearch Cigarettes #1
Receives: Other: Cigarettes with varying nicotine content
RC 2 onlyExperimentalResearch Cigarettes #2
Receives: Other: Cigarettes with varying nicotine content
RC 2 + EC 1ExperimentalResearch Cigarettes #2 plus E-cigarettes #1
Receives: Other: Cigarettes with varying nicotine content; Other: E-Cigarettes
RC 2 + EC 2ExperimentalResearch Cigarettes #2 plus E-cigarettes #2
Receives: Other: Cigarettes with varying nicotine content; Other: E-Cigarettes

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Cigarettes Smoked 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.

  1. First posted17 Sep 2019
  2. Study start18 Oct 2020
  3. Primary completion27 Nov 2023
  4. Study completion27 Nov 2023

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04092101
Sponsor's protocol ID
CHRMS19-0130
Other IDs
U54DA036114-06
Status last verified
Mar 2025
First submitted
13 Sep 2019
Last updated
30 Mar 2025
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 42560883
  • Higgins 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cigarettes with varying nicotine content and E-Cigarettes in people with Tobacco Use Disorder, run by University of Vermont 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 30 Mar 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 30 Mar 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?

Number of Cigarettes Smoked 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 NCT04092101, 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 30 Mar 2025.

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