Smoking
Conditions
Keywords
Smoking, Non-daily smokers, Ecological Momentary Assessment, Biomarkers
Brief summary
The purpose of this research study is to investigate the impact of different nicotine levels in cigarettes among non-daily smokers. This research may help inform the Food and Drug Administration (FDA) on how best to regulate tobacco products in the future, with the goal of improving public health.
Detailed description
The overall goal of the study is to assess the effects of switching to Very-Low-Nicotine-Content cigarettes (VLNCCs) among non-daily, or intermittent smokers (ITS). This is a two-arm randomized study with an own-cigarette baseline control. After a 2-week baseline period smoking their own cigarettes, 455 ITS will be randomized (double-blind) for 10 weeks to smoke experimental cigarettes, either: (a) normal nicotine content cigarettes (NNCCs; 0.8 mg) or (b) VLNCCs (0.07 mg), each matched to menthol status of subjects' preferred brand. ITS are more likely to be African-American (AA) smokers; thus AA smokers will be oversampled (to one third of the total sample). Change in cigarette consumption is the primary end-point, and biomarkers of smoke exposure and measures of smoking intensity are also assessed.
Interventions
0.07 mg nicotine delivery
0.8 mg nicotine delivery
Sponsors
National Cancer Institute (NCI)
Saul Shiffman
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age 18 years or older, and smoking cigarettes for at least 3 years * smoking, on average, 4-27 days per month * smoking at current rate for at least the previous 3 months * willingness to try novel cigarettes
Exclusion criteria
* active plans to quit or actively seeking smoking cessation treatment in the next 3 months * severe psychiatric disorders that may interfere with study procedures * current, regular (i.e., monthly or more) use of nicotine replacement or other tobacco products, by self-report * exclusive use of roll-your-own cigarettes (since the study uses manufactured cigarettes) * \[for female participants\] being pregnant or breastfeeding, or planning to become pregnant, by self-report * current use of medications such as Chantix (varenicline), Zyban, Wellbutrin, or bupropion for any purpose, including stopping smoking * occurrence of heart attack, stroke, or angina in the past 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cigarette Consumption | Two-week pre-intervention baseline period compared to final two weeks of 10-week intervention period | Difference in mean daily cigarette consumption between initial two-week baseline period and final two weeks of experimental period, using imputed data |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exposure Measure - Solanesol | Post-randomization time points at study weeks 4, 8, 12 | The concentration of solanesol, a stable marker indicator of how much smoke has passed through the filter of a smoked cigarette to the smoker, will be assayed as a measure of smoking intensity. The filter of a cigarette butts smoked during the baseline period will be compared to those smoked during the experimental period. |
| Exposure Measure - Smoking Topography | Post-randomization study visits at study weeks 4, 8, 12 | Difference between average puff volume per cigarette at laboratory smoking topography sessions at study weeks 4, 8, and 12 across all participants, comparing those assigned to the very-low-nicotine-content cigarette condition to those assigned to the normal-nicotine-content cigarette condition. Topography measures were averaged across all time points for each treatment group. |
| Exposure Measure - Cotinine (Logged) | Post-randomization office visits weeks 2 (end of baseline period) and 12 (end of study) | Cotinine nicotine exposure measure, analyzed from urine samples taken at study office visits The natural logarithm (ln) of the cotinine measures was used for analysis. Difference in ln(cotinine) between baseline and end of study, from imputed data |
| Exposure Measure - Cigarette Butt Weight | Entire length of study, through completion, up to 12 weeks | Mean mass smoked per cigarette (calculated as the starting cigarette weight minus returned butt weight) aggregated for all cigarettes smoked among participants assigned to the very-low-nicotine-content cigarette, compared to those assigned to the normal-nicotine-content cigarette condition. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the greater Pittsburgh area from June 2015 through April 2017 via various channels (e.g., advertisements on local television stations, public transportation, and social media such as Facebook and Instagram), as well as through University-housed research registries and recruiting services.
Pre-assignment details
Participants may have been excluded from the study after enrollment but before assignment to an arm if they were found to be unable to adhere to the study protocol or were unable to attend study visits, opted to no longer participate, or if they became unable to contact (i.e., were lost to follow-up).
Participants by arm
| Arm | Count |
|---|---|
| Very Low Nicotine Content Cigarettes Very low nicotine content cigarettes: 0.07 mg nicotine delivery | 118 |
| Normal Nicotine Content Cigarettes Normal nicotine content cigarettes: 0.8 mg nicotine delivery | 120 |
| Total | 238 |
Baseline characteristics
| Characteristic | Very Low Nicotine Content Cigarettes | Normal Nicotine Content Cigarettes | Total |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 13.5 | 38.4 years STANDARD_DEVIATION 14.2 | 37.9 years STANDARD_DEVIATION 13.8 |
| Cigarettes per day at enrollment (across all days) | 1.9 cigarettes per day STANDARD_DEVIATION 1.6 | 1.9 cigarettes per day STANDARD_DEVIATION 1.7 | 1.9 cigarettes per day STANDARD_DEVIATION 1.7 |
| Cigarettes per day at enrollment (smoking days only) | 3.3 cigarettes per day STANDARD_DEVIATION 2.3 | 3.5 cigarettes per day STANDARD_DEVIATION 2.9 | 3.4 cigarettes per day STANDARD_DEVIATION 2.6 |
| Previous history of daily smoking | 57 Participants | 61 Participants | 118 Participants |
| Race/Ethnicity, Customized Race Black | 27 Participants | 34 Participants | 61 Participants |
| Race/Ethnicity, Customized Race Other | 15 Participants | 10 Participants | 25 Participants |
| Race/Ethnicity, Customized Race White | 76 Participants | 76 Participants | 152 Participants |
| Region of Enrollment United States | 118 participants | 120 participants | 238 participants |
| Sex: Female, Male Female | 59 Participants | 71 Participants | 130 Participants |
| Sex: Female, Male Male | 59 Participants | 49 Participants | 108 Participants |
| Smoking days per week at enrollment | 3.7 smoking days per week STANDARD_DEVIATION 1.4 | 3.7 smoking days per week STANDARD_DEVIATION 1.4 | 3.7 smoking days per week STANDARD_DEVIATION 1.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 118 | 0 / 120 |
| other Total, other adverse events | 41 / 118 | 42 / 120 |
| serious Total, serious adverse events | 1 / 118 | 2 / 120 |
Outcome results
Primary
Change in Cigarette Consumption
Difference in mean daily cigarette consumption between initial two-week baseline period and final two weeks of experimental period, using imputed data
Time frame: Two-week pre-intervention baseline period compared to final two weeks of 10-week intervention period
Population: All participants who were randomized to an experimental condition (either very-low-nicotine-content cigarettes or normal-nicotine-content cigarettes)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Change in Cigarette Consumption | -1.6 cigarettes per day |
| Normal Nicotine Content Cigarettes | Change in Cigarette Consumption | -0.05 cigarettes per day |
p-value: <0.00195% CI: [0.86, 2.17]ANCOVA
Secondary
Exposure Measure - Cigarette Butt Weight
Mean mass smoked per cigarette (calculated as the starting cigarette weight minus returned butt weight) aggregated for all cigarettes smoked among participants assigned to the very-low-nicotine-content cigarette, compared to those assigned to the normal-nicotine-content cigarette condition.
Time frame: Entire length of study, through completion, up to 12 weeks
Population: Analysis population consists of those participants who contributed data to the study for (at minimum) the two-week baseline study period block as well as the first two-week block post-randomization
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Exposure Measure - Cigarette Butt Weight | 0.58 grams | Standard Error 0.01 |
| Normal Nicotine Content Cigarettes | Exposure Measure - Cigarette Butt Weight | 0.60 grams | Standard Error 0.01 |
p-value: 0.0395% CI: [-0.04, -0.002]Mixed Models Analysis
Secondary
Exposure Measure - Cotinine (Logged)
Cotinine nicotine exposure measure, analyzed from urine samples taken at study office visits The natural logarithm (ln) of the cotinine measures was used for analysis. Difference in ln(cotinine) between baseline and end of study, from imputed data
Time frame: Post-randomization office visits weeks 2 (end of baseline period) and 12 (end of study)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Exposure Measure - Cotinine (Logged) | -0.84 log ng/mL |
| Normal Nicotine Content Cigarettes | Exposure Measure - Cotinine (Logged) | -0.15 log ng/mL |
p-value: 0.01695% CI: [-1.26, -0.13]ANCOVA
Secondary
Exposure Measure - Smoking Topography
Difference between average puff volume per cigarette at laboratory smoking topography sessions at study weeks 4, 8, and 12 across all participants, comparing those assigned to the very-low-nicotine-content cigarette condition to those assigned to the normal-nicotine-content cigarette condition. Topography measures were averaged across all time points for each treatment group.
Time frame: Post-randomization study visits at study weeks 4, 8, 12
Population: Analysis consists of those participants who contributed data to the study through at least study week 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Exposure Measure - Smoking Topography | 501.20 mL | Standard Error 13.5 |
| Normal Nicotine Content Cigarettes | Exposure Measure - Smoking Topography | 539.70 mL | Standard Error 12.83 |
p-value: 0.04195% CI: [-75.21, -1.78]Mixed Models Analysis
Secondary
Exposure Measure - Solanesol
The concentration of solanesol, a stable marker indicator of how much smoke has passed through the filter of a smoked cigarette to the smoker, will be assayed as a measure of smoking intensity. The filter of a cigarette butts smoked during the baseline period will be compared to those smoked during the experimental period.
Time frame: Post-randomization time points at study weeks 4, 8, 12
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Exposure Measure - Solanesol | NA mg/butt |
| Normal Nicotine Content Cigarettes | Exposure Measure - Solanesol | NA mg/butt |