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CompletedNCT04092101Updated Mar 30, 2025Results posted

Low Nicotine Content Cigarettes in Vulnerable Populations: Opioid Use Disorder

A Phase 2 interventional study of Cigarettes with varying nicotine content and E-Cigarettes in Tobacco Use Disorder, sponsored by University of Vermont. Completed at 2 sites in United States. Open to participants aged 21 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-03-30.

Sponsored by University of Vermont · Phase 2, Interventional, and Basic science

Phase
Phase 2
Study type
Interventional
Enrollment
326
Allocation
Randomized
Ages
21 Years to 70 Years
Sex
All
01

Study 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. 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.

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.

02

Conditions studied

  • Tobacco Use Disorder

Keywords

  • Biomarkers of Exposure
  • Compensatory Smoking
  • Nicotine Dependence
  • Reduced Nicotine Cigarettes
  • Affective Disorders
  • Tobacco Withdrawal
  • Vulnerable Populations
  • E-Cigarettes
03

In context

Opioid-Related Disorders

1,411 studies on the registry are indexed under Opioid-Related Disorders; 290 are open to participants now.

This study's enrollment of 326 is above the median of 63 across 1,123 interventional studies indexed under Opioid-Related Disorders.

Browse Opioid-Related Disorders studies →

Lead sponsor

University of Vermont is the lead sponsor of 215 studies on the registry; 28 are open to participants now.

Of its 16 completed or terminated interventional studies of FDA-regulated products, 9 (56%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
21 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Maintained on opioid medication
  • 21 to 70 years old

Exclusion criteria

Exclusion Criteria:

  • Not maintained on opioid medication
  • Under 21 years old
  • Over 70 years old
05

Study design

Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
326 participants (actual)

Study arms

  • Experimental
    RC 1 only

    Research Cigarettes #1

    Other: Cigarettes with varying nicotine content

  • Experimental
    RC 2 only

    Research Cigarettes #2

    Other: Cigarettes with varying nicotine content

  • Experimental
    RC 2 + EC 1

    Research Cigarettes #2 plus E-cigarettes #1

    Other: Cigarettes with varying nicotine content · Other: E-Cigarettes

  • Experimental
    RC 2 + EC 2

    Research Cigarettes #2 plus E-cigarettes #2

    Other: Cigarettes with varying nicotine content · Other: E-Cigarettes

Interventions

  • OtherCigarettes with varying nicotine content

    1) Altering the nicotine content of the tobacco research cigarette

  • OtherE-Cigarettes

    1) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition

06

What researchers measure

Primary outcomes

  1. Number of Cigarettes Smoked Per Day

    Cigarettes per day will be assessed for use of cigarettes with different nicotine content.

    Time frame: 16 weeks

07

Results

Posted Mar 30, 2025

Participant flow

Participant flow — Overall Study
MilestoneRC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2
Started83857484
Completed67665770
Not completed16191714

Outcome measures

PrimaryNumber of Cigarettes Smoked Per Day

Cigarettes per day will be assessed for use of cigarettes with different nicotine content.

Time frame:
16 weeks
Reported as:
Least squares mean · cigarettes per day
Number of Cigarettes Smoked Per Day
cigarettes per dayRC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2
Number of Cigarettes Smoked Per Day22.54 ± 1.5914.32 ± 1.3211.76 ± 1.187.63 ± 0.90

Adverse events

Collected over 16 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
RC 1 Only0/83 (0%)9/83 (10.8%)71/83 (85.5%)
RC 2 Only0/85 (0%)4/85 (4.7%)74/85 (87.1%)
RC 2 + EC 11/74 (1.4%)4/74 (5.4%)62/74 (83.8%)
RC 2 + EC 20/84 (0%)2/84 (2.4%)72/84 (85.7%)
Most frequent serious events
Showing 10 of 15
Most frequent serious events
EventRC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2
Psychiatric disorders - OtherPsychiatric disorders3/830/850/740/84
HypertensionVascular disorders1/830/851/740/84
Death NOSGeneral disorders0/830/851/740/84
Injury, poisoning, and procedural complicationsInjury, poisoning and procedural complications0/830/851/740/84
DehydrationMetabolism and nutrition disorders0/830/851/740/84
Esophageal perforationGastrointestinal disorders1/830/850/740/84
IrritabilityGeneral disorders1/830/850/740/84
Tumor PainNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/830/850/740/84
Pregnancy, puerperium, and perinatal conditionsPregnancy, puerperium and perinatal conditions1/830/850/740/84
Surgical and medical procedures - OtherSurgical and medical procedures1/831/850/740/84
Most frequent other events
Showing 10 of 13
Most frequent other events
EventRC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2
OASIS Score IncreasePsychiatric disorders32/8331/8531/7431/84
BDI Category IncreasePsychiatric disorders29/8329/8526/7425/84
Psychiatric disordersPsychiatric disorders27/8328/8519/7424/84
Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders23/8327/8518/7418/84
General disorders and administrationGeneral disorders18/8324/8516/7422/84
Infections and infestationsInfections and infestations16/8323/858/7410/84
Nervous system disordersNervous system disorders7/8318/8515/7410/84
Gastrointestinal disordersGastrointestinal disorders9/8317/8514/7417/84
Vascular disordersVascular disorders10/8313/858/7416/84
Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders11/8316/857/7412/84

Baseline characteristics

Age, Continuous
Age, Continuous(years)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
Mean39.77 ± 10.9839.85 ± 9.2841.51 ± 12.3939.38 ± 10.5940.09 ± 10.79
Sex: Female, Male
Sex: Female, Male(Participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
Female65695059243
Male1816242583
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
Hispanic or Latino433212
Not Hispanic or Latino79827182314
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
American Indian or Alaska Native11002
Asian00011
Native Hawaiian or Other Pacific Islander00000
Black or African American1069934
White67706168266
More than one race471416
Unknown or Not Reported11327
Region of Enrollment
Region of Enrollment(participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
United States83857484326
Population
Population(Participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
Females with lower educational level2023162180
Opioid Use Disorder1919171974
Affective disorders44434144172
Educational level
Educational level(Participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
<High school9431430
High school graduate, equivalency, or some college51574647201
Associate's degree811131143
≥College graduate1513121252
Marital status
Marital status(Participants)RC 1 OnlyRC 2 OnlyRC 2 + EC 1RC 2 + EC 2Total
Married815171151
Never married49473648180
Divorced, separated, or widowed2623212595

8 further baseline measures are reported on the registry.

08

Study locations

2 sites
  • Johns Hopkins University
    Baltimore, Maryland 21287, United States
  • Shirley Plucinski
    Burlington, Vermont 05401, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 23, 2023
  • Informed consent form · Jan 23, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04092101
Lead sponsor
University of Vermont
Collaborators
Food and Drug Administration (FDA), National Institute on Drug Abuse (NIDA), Johns Hopkins University
Responsible party
Stacey C. Sigmon (Professor, University of Vermont) — Principal investigator
First posted
Sep 17, 2019
Start date
Oct 18, 2020
Primary completion
Nov 27, 2023
Completion
Nov 27, 2023
Results posted
Mar 30, 2025
Last update
Mar 30, 2025

Study contacts

Stacey C. Sigmon, Ph.D.
principal investigator · University of Vermont

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2025. You cannot join it, but the record below documents what was studied.

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