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
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.
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 →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.
Exclusion Criteria:
Research Cigarettes #1
Other: Cigarettes with varying nicotine content
Research Cigarettes #2
Other: Cigarettes with varying nicotine content
Research Cigarettes #2 plus E-cigarettes #1
Other: Cigarettes with varying nicotine content · Other: E-Cigarettes
Research Cigarettes #2 plus E-cigarettes #2
Other: Cigarettes with varying nicotine content · Other: E-Cigarettes
1) Altering the nicotine content of the tobacco research cigarette
1) Altering the availability of e-cigarettes; 2) Altering option to personalize the e-liquid in the e-cig condition
Number of Cigarettes Smoked Per Day
Cigarettes per day will be assessed for use of cigarettes with different nicotine content.
Time frame: 16 weeks
| Milestone | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 |
|---|---|---|---|---|
| Started | 83 | 85 | 74 | 84 |
| Completed | 67 | 66 | 57 | 70 |
| Not completed | 16 | 19 | 17 | 14 |
Cigarettes per day will be assessed for use of cigarettes with different nicotine content.
| cigarettes per day | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 |
|---|---|---|---|---|
| Number of Cigarettes Smoked Per Day | 22.54 ± 1.59 | 14.32 ± 1.32 | 11.76 ± 1.18 | 7.63 ± 0.90 |
Collected over 16 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| RC 1 Only | 0/83 (0%) | 9/83 (10.8%) | 71/83 (85.5%) |
| RC 2 Only | 0/85 (0%) | 4/85 (4.7%) | 74/85 (87.1%) |
| RC 2 + EC 1 | 1/74 (1.4%) | 4/74 (5.4%) | 62/74 (83.8%) |
| RC 2 + EC 2 | 0/84 (0%) | 2/84 (2.4%) | 72/84 (85.7%) |
| Event | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 |
|---|---|---|---|---|
| Psychiatric disorders - OtherPsychiatric disorders | 3/83 | 0/85 | 0/74 | 0/84 |
| HypertensionVascular disorders | 1/83 | 0/85 | 1/74 | 0/84 |
| Death NOSGeneral disorders | 0/83 | 0/85 | 1/74 | 0/84 |
| Injury, poisoning, and procedural complicationsInjury, poisoning and procedural complications | 0/83 | 0/85 | 1/74 | 0/84 |
| DehydrationMetabolism and nutrition disorders | 0/83 | 0/85 | 1/74 | 0/84 |
| Esophageal perforationGastrointestinal disorders | 1/83 | 0/85 | 0/74 | 0/84 |
| IrritabilityGeneral disorders | 1/83 | 0/85 | 0/74 | 0/84 |
| Tumor PainNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/83 | 0/85 | 0/74 | 0/84 |
| Pregnancy, puerperium, and perinatal conditionsPregnancy, puerperium and perinatal conditions | 1/83 | 0/85 | 0/74 | 0/84 |
| Surgical and medical procedures - OtherSurgical and medical procedures | 1/83 | 1/85 | 0/74 | 0/84 |
| Event | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 |
|---|---|---|---|---|
| OASIS Score IncreasePsychiatric disorders | 32/83 | 31/85 | 31/74 | 31/84 |
| BDI Category IncreasePsychiatric disorders | 29/83 | 29/85 | 26/74 | 25/84 |
| Psychiatric disordersPsychiatric disorders | 27/83 | 28/85 | 19/74 | 24/84 |
| Respiratory, thoracic and mediastinal disordersRespiratory, thoracic and mediastinal disorders | 23/83 | 27/85 | 18/74 | 18/84 |
| General disorders and administrationGeneral disorders | 18/83 | 24/85 | 16/74 | 22/84 |
| Infections and infestationsInfections and infestations | 16/83 | 23/85 | 8/74 | 10/84 |
| Nervous system disordersNervous system disorders | 7/83 | 18/85 | 15/74 | 10/84 |
| Gastrointestinal disordersGastrointestinal disorders | 9/83 | 17/85 | 14/74 | 17/84 |
| Vascular disordersVascular disorders | 10/83 | 13/85 | 8/74 | 16/84 |
| Musculoskeletal and connective tissue disordersMusculoskeletal and connective tissue disorders | 11/83 | 16/85 | 7/74 | 12/84 |
| Age, Continuous(years) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| Mean | 39.77 ± 10.98 | 39.85 ± 9.28 | 41.51 ± 12.39 | 39.38 ± 10.59 | 40.09 ± 10.79 |
| Sex: Female, Male(Participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| Female | 65 | 69 | 50 | 59 | 243 |
| Male | 18 | 16 | 24 | 25 | 83 |
| Ethnicity (NIH/OMB)(Participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 4 | 3 | 3 | 2 | 12 |
| Not Hispanic or Latino | 79 | 82 | 71 | 82 | 314 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 1 | 0 | 0 | 2 |
| Asian | 0 | 0 | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 10 | 6 | 9 | 9 | 34 |
| White | 67 | 70 | 61 | 68 | 266 |
| More than one race | 4 | 7 | 1 | 4 | 16 |
| Unknown or Not Reported | 1 | 1 | 3 | 2 | 7 |
| Region of Enrollment(participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| United States | 83 | 85 | 74 | 84 | 326 |
| Population(Participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| Females with lower educational level | 20 | 23 | 16 | 21 | 80 |
| Opioid Use Disorder | 19 | 19 | 17 | 19 | 74 |
| Affective disorders | 44 | 43 | 41 | 44 | 172 |
| Educational level(Participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| <High school | 9 | 4 | 3 | 14 | 30 |
| High school graduate, equivalency, or some college | 51 | 57 | 46 | 47 | 201 |
| Associate's degree | 8 | 11 | 13 | 11 | 43 |
| ≥College graduate | 15 | 13 | 12 | 12 | 52 |
| Marital status(Participants) | RC 1 Only | RC 2 Only | RC 2 + EC 1 | RC 2 + EC 2 | Total |
|---|---|---|---|---|---|
| Married | 8 | 15 | 17 | 11 | 51 |
| Never married | 49 | 47 | 36 | 48 | 180 |
| Divorced, separated, or widowed | 26 | 23 | 21 | 25 | 95 |
8 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes
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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University of Vermont