Carcinogenesis, Harm Reduction, Oral Nicotine Pouch Use, Smoking Behaviors, Tobacco Use Disorder, Toxic Effect of Tobacco and Nicotine
Conditions
Brief summary
This study aims to assess the feasibility, acceptability, and the potential harm reduction of switching to potentially lower risk, oral nicotine pouches in adult smokers. Part One of this study aims to assess the interest of current smokers in switching to an e-cigarette device (i.e. JUUL) compared to alternative non-combustible tobacco products (i.e. smokeless tobacco/snus) and/or medicinal nicotine via survey. Part Two will consist of a pilot study of 30 non-treatment seeking adult smokers to investigate within-person changes in smoking behavior as a result of switching to different concentrations of oral nicotine pouch products (i.e. ZYN, 3mg and 6mg nicotine concentration). Additionally, by measuring bio-markers of tobacco exposure from baseline, this will allow the study to assess the potential for harm reduction in switching from cigarettes to oral nicotine pouches.
Interventions
DEVICEZYN
30 current non-treatment seeking adult smokers will be switched from smoking cigarettes to ZYN oral nicotine pouches containing either 3mg or 6mg concentration nicotine salts.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Intervention model description
30 current non-treatment seeking adult smokers will be randomized to either the 3mg or 6mg nicotine concentration ZYN condition.
Eligibility
Sex/Gender
ALL
Age
21 Years to 77 Years
Healthy volunteers
No
Inclusion criteria
1. 21-77 years old(in line with NIH guidelines for 18+ being the age of consent in adults) (2008 PHS Guideline Update Panel) 2. English literate 3. Smoke at least 1 cigarette per day 4. Expired breath carbon monoxide level ≥ 6ppm at baseline 5. Not currently actively pursuing smoking cessation services or planning to use evidence-based cessation tools to quit in the next month 6. Not interested in the use of existing FDA-approved tobacco pharmacotherapies (i.e., NRT, wellbutrin, varenicline).
Exclusion criteria
1. Currently using any stop smoking treatments (2008 PHS Guideline Update Panel) 2. History of serious psychiatric condition (i.e., bipolar disorder, schizophrenia) 3. Current uncontrolled medical condition 4. Cardiac conditions that required a hospitalization or intensive treatment on an outpatient basis in the past year including: myocardial infarction, coronary artery disease, unstable angina, congestive heart failure, or tachyarrhythmias (including rapid atrial fibrillation, ventricular tachycardia, or ventricular fibrillation) 5. Female participants of child-bearing age will be excluded if they are currently pregnant or breastfeeding or report an unwillingness to use effective birth control (i.e., abstinence, IUD, implant, sterilization, pill, patch, ring, or barrier method such as condoms) for the duration of the study 6. Severe lung disease that requires supplemental oxygen 7. Uncontrolled asthma (\<20 on the Asthma Control Test (ACT) or requiring steroids more than 1x per year) 8. Unstable COPD: defined as GOLD category C or D (more than 2 exacerbations or 1 exacerbation leading to hospitalization in the past year) 9. Planning to quit smoking with a set goal or time for quit attempt 10. Known hypersensitivity to propylene glycol 11. Patients with an FEV1 \< 40%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Cigarettes Smoked Per Day (Log-transformed) | up to week 4 | The investigators will compare whether smoking behavior varies by the 3mg and 6mg nicotine concentrations as measure by the standardized Timeline Followback Interview. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Switched From Cigarettes to the ZYN Pouches. | This will be evaluated at week 4. | To investigate whether switching behavior varies by the 3mg and 6mg nicotine concentrations |
| Percentage of Smoke Free Days. | up to week 4 | The investigators will compare whether the smoke free days vary by the 3mg and 6mg nicotine concentrations |
| Level of Biomarker (NNAL) Among Smokers | baseline and week 4 | Participants will provide repeated lab samples for biomarker assessments. Urine samples obtained will be compared at baseline and week 4 for differences by group and by time. |
| Subjective Effects of Oral Nicotine Pouches | week 4 | To evaluate the acceptability of switching, participants will also be asked how likely it is that they will continue to use ZYN oral nicotine patches for cigarette substitution compared to cigarettes on a question designed for this trial. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3mg Nicotine Concentration 15 participants will be randomly assigned to receive ZYN Pouches with 3mg nicotine concentration.
ZYN: 30 current non-treatment seeking adult smokers will be switched from smoking cigarettes to ZYN oral nicotine pouches containing either 3mg or 6mg concentration nicotine salts. | 15 |
| 6mg Nicotine Concentration 15 participants will be randomly assigned to receive ZYN Pouches with 6mg nicotine concentration.
ZYN: 30 current non-treatment seeking adult smokers will be switched from smoking cigarettes to ZYN oral nicotine pouches containing either 3mg or 6mg concentration nicotine salts. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | 3mg Nicotine Concentration | 6mg Nicotine Concentration |
|---|---|---|---|
| Age, Continuous | 56.83 years STANDARD_DEVIATION 11.6 | 58.20 years STANDARD_DEVIATION 9.7 | 55.47 years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 15 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Customized Black/African American | 11 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Customized Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Customized White/Caucasian | 18 Participants | 12 Participants | 6 Participants |
| Region of Enrollment United States | 30 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 18 Participants | 9 Participants | 9 Participants |
| Sex: Female, Male Male | 12 Participants | 6 Participants | 6 Participants |
| Smoke within 30 minutes of waking No | 10 Participants | 5 Participants | 5 Participants |
| Smoke within 30 minutes of waking Yes | 20 Participants | 10 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 13 / 15 | 13 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Number of Cigarettes Smoked Per Day (Log-transformed)
The investigators will compare whether smoking behavior varies by the 3mg and 6mg nicotine concentrations as measure by the standardized Timeline Followback Interview.
Time frame: up to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3mg Nicotine Concentration | Number of Cigarettes Smoked Per Day (Log-transformed) | 2.0 number of cigarettes smoked | Standard Deviation 0.1 |
| 6mg Nicotine Concentration | Number of Cigarettes Smoked Per Day (Log-transformed) | 1.8 number of cigarettes smoked | Standard Deviation 0.1 |
Secondary
Level of Biomarker (NNAL) Among Smokers
Participants will provide repeated lab samples for biomarker assessments. Urine samples obtained will be compared at baseline and week 4 for differences by group and by time.
Time frame: baseline and week 4
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| 3mg Nicotine Concentration | Level of Biomarker (NNAL) Among Smokers | Baseline | 17.26 pg/mL | Standard Error 1.89 |
| 3mg Nicotine Concentration | Level of Biomarker (NNAL) Among Smokers | Week 4 | 18.55 pg/mL | Standard Error 1.94 |
| 6mg Nicotine Concentration | Level of Biomarker (NNAL) Among Smokers | Baseline | 15.98 pg/mL | Standard Error 1.89 |
| 6mg Nicotine Concentration | Level of Biomarker (NNAL) Among Smokers | Week 4 | 16.04 pg/mL | Standard Error 1.91 |
Secondary
Number of Participants Who Switched From Cigarettes to the ZYN Pouches.
To investigate whether switching behavior varies by the 3mg and 6mg nicotine concentrations
Time frame: This will be evaluated at week 4.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3mg Nicotine Concentration | Number of Participants Who Switched From Cigarettes to the ZYN Pouches. | 0 Participants |
| 6mg Nicotine Concentration | Number of Participants Who Switched From Cigarettes to the ZYN Pouches. | 2 Participants |
Secondary
Percentage of Smoke Free Days.
The investigators will compare whether the smoke free days vary by the 3mg and 6mg nicotine concentrations
Time frame: up to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3mg Nicotine Concentration | Percentage of Smoke Free Days. | 8.57 percentage of smoke free days | Standard Deviation 22.42 |
| 6mg Nicotine Concentration | Percentage of Smoke Free Days. | 11.22 percentage of smoke free days | Standard Deviation 24.58 |
p-value: 0.601Wilcoxon (Mann-Whitney)
Secondary
Subjective Effects of Oral Nicotine Pouches
To evaluate the acceptability of switching, participants will also be asked how likely it is that they will continue to use ZYN oral nicotine patches for cigarette substitution compared to cigarettes on a question designed for this trial.
Time frame: week 4
Population: This measure was not used in the study and therefore data were not collected.