Tobacco Dependence
Conditions
Keywords
Smoking, Nicotine
Brief summary
The overall goal of this study is to address the question of whether progressively lowering nicotine content in cigarettes can reduce or eliminate nicotine dependence in smokers of low socioeconomic status
Detailed description
To address the question of whether progressively lowering nicotine content in cigarettes can reduce or eliminate nicotine dependence in low socioeconomic smokers, we will randomize smokers to either an Reduced Nicotine Content group with a gradual step-wise reduction in nicotine from 11 mg to 0.2 mg per cigarette in five 3-wk stages, or a control group with nicotine content similar to their preferred usual brand of cigarettes. Overall, we hypothesize that low socioeconomic smokers who switch to progressively lower nicotine cigarettes will initially alter their smoking behavior to compensate for lower nicotine until cigarette nicotine yields become so low that complete compensation becomes too difficult. At that point, smokers will either drop-out or continue to smoke the reduced nicotine content cigarettes but with incomplete compensatory behaviors.
Interventions
Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette
DRUGSame Nicotine Content Cigarettes
about 11.6 mg nicotine per cigarette
Sponsors
George Washington University
National Institute on Drug Abuse (NIDA)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18-65 * Less than 16 years of education * Able to understand, and sign consent * Smoke \>4 cigarettes/day for at least a year * No quit attempt in prior 1 month and not planning to quit smoking within next 6 months * Plan to live in local area for next 8 months * Able to read and write in English * Women not pregnant and taking steps to avoid pregnancy
Exclusion criteria
* College graduate * Use of psychotropic drugs * Significant medical condition, or immune system disorders, respiratory diseases, kidney or liver diseases or any other medical disorders that may affect biomarker data * Use of any non-cigarette nicotine delivery product in the past week or smoking cessation medicine in prior 3 months * Currently pregnant or nursing * Uncontrolled serious psychotic illness or substance abuse * History of difficulties providing blood samples-fainting, poor veins, anxiety
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Dropped Out of Study as a Measure of Adherence | 18 weeks | Adherence to the regimen was assessed via dropout (due to withdrawal or lost-to-follow up) during the randomized intervention trial phase of the study. Dropout was analyzed as a time-to-event outcome during the 18 weeks after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predictors of Participant Dropout | 18 weeks | Baseline participant characteristics were evaluated for their association with the primary outcome, randomized trial phase dropout. The table below reports the number of participants who dropped out by each characteristic that was found to be univariately associated with the primary outcome. |
| Cigarettes Per Day | 18 weeks | Measured by self-reported cigarettes per day at in-person clinic visits using 6-day follow back |
| Perceived Stress | 18 weeks | Perceived Stress is measured via the Perceived Stress Scale Score. The 10-item version was used. Scale range is 0-40. Higher scores indicate more stress. |
| Smoke Exposure | 18 weeks | Measured in carbon monoxide levels by expired CO |
| Cortisol | 15 weeks | Salivary Cortisol Cortisol is produced by the hypothalamic-pituitary-adrenal axis (HPA) axis in response to stress. Peak cortisol measures during the cortisol awakening response were used. |
| Nicotine Exposure | 18 weeks | Measured by cotinine (ng/ml) measured in plasma |
Countries
United States
Participant flow
Pre-assignment details
Participants completed a baseline phase of one week on usual brand cigarettes and another baseline phase on same nicotine content cigarettes (2 weeks). Of these, 35 participants either were lost to follow up or withdrawn from the study during the baseline phase and before they started the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Reduced Nicotine Content Cigarettes The experimental group will smoke cigarettes with Gradually Reduced Nicotine Content (RNC) (11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg per cigarette) cigarettes, each smoked for 3 weeks, except for the last period which will last 6 weeks to evaluate a longer-term adherence to the lowest nicotine content cigarette.
Reduced Nicotine Content Cigarettes: Cigarettes contain 11.6, 7.4, 3.3, 1.4, 0.7, and 0.2 mg nicotine per cigarette | 122 |
| Same Nicotine Content Cigarettes The Same Nicotine Control Group (SNC) will continue to smoke research cigarettes with a usual nicotine content (about 11.6 mg per cigarette)
Same Nicotine Content Cigarettes: about 11.6 mg nicotine per cigarette | 123 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 26 | 11 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 22 | 7 |
Baseline characteristics
| Characteristic | Same Nicotine Content Cigarettes | Total | Reduced Nicotine Content Cigarettes |
|---|---|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 10.8 | 44.9 years STANDARD_DEVIATION 11.4 | 44.7 years STANDARD_DEVIATION 12.1 |
| Cigarettes per Day | 24 cigarettes STANDARD_DEVIATION 13.9 | 24.1 cigarettes STANDARD_DEVIATION 12.5 | 24.2 cigarettes STANDARD_DEVIATION 11 |
| Education < High School Degree | 25 Participants | 40 Participants | 15 Participants |
| Education High School Degree | 57 Participants | 112 Participants | 55 Participants |
| Education > High School Degree and < Bachelor's degree | 41 Participants | 93 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 6 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants | 237 Participants | 117 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Exhaled Carbon Monoxide | 31.3 parts per million STANDARD_DEVIATION 15.8 | 31.4 parts per million STANDARD_DEVIATION 16.5 | 31.5 parts per million STANDARD_DEVIATION 17.2 |
| Menthol smoker | 85 Participants | 170 Participants | 85 Participants |
| Perceived Stress Scale Score | 12.1 units on a scale STANDARD_DEVIATION 7.2 | 12.3 units on a scale STANDARD_DEVIATION 6.9 | 12.6 units on a scale STANDARD_DEVIATION 6.7 |
| Plasma Cotinine | 260.3 ng/ml STANDARD_DEVIATION 148.5 | 260.9 ng/ml STANDARD_DEVIATION 148.3 | 261.6 ng/ml STANDARD_DEVIATION 148.6 |
| Race/Ethnicity, Customized African American/black | 35 Participants | 78 Participants | 43 Participants |
| Race/Ethnicity, Customized American Indian/Alaskan native | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian/white | 82 Participants | 153 Participants | 71 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Island | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 6 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 123 participants | 245 participants | 122 participants |
| Sex: Female, Male Female | 72 Participants | 128 Participants | 56 Participants |
| Sex: Female, Male Male | 51 Participants | 117 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 122 | 1 / 123 |
| other Total, other adverse events | 54 / 122 | 63 / 123 |
| serious Total, serious adverse events | 11 / 122 | 11 / 123 |
Outcome results
Primary
Number of Participants Who Dropped Out of Study as a Measure of Adherence
Adherence to the regimen was assessed via dropout (due to withdrawal or lost-to-follow up) during the randomized intervention trial phase of the study. Dropout was analyzed as a time-to-event outcome during the 18 weeks after randomization.
Time frame: 18 weeks
Population: All randomized participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Number of Participants Who Dropped Out of Study as a Measure of Adherence | 52 Participants |
| Same Nicotine Content Cigarettes | Number of Participants Who Dropped Out of Study as a Measure of Adherence | 19 Participants |
p-value: <0.000195% CI: [1.95, 5.58]Regression, Cox
Secondary
Cigarettes Per Day
Measured by self-reported cigarettes per day at in-person clinic visits using 6-day follow back
Time frame: 18 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Cigarettes Per Day | 21.0 cigarettes per day |
| Same Nicotine Content Cigarettes | Cigarettes Per Day | 25.1 cigarettes per day |
p-value: 0.000695% CI: [-6.44, -1.75]Mixed Models Analysis
Secondary
Cortisol
Salivary Cortisol Cortisol is produced by the hypothalamic-pituitary-adrenal axis (HPA) axis in response to stress. Peak cortisol measures during the cortisol awakening response were used.
Time frame: 15 weeks
Population: A subset of participants was randomly selected to complete the cortisol collection procedure and those who provided usable samples 1-3 were used in this analysis
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Cortisol | 0.32 ng/dl |
| Same Nicotine Content Cigarettes | Cortisol | 0.48 ng/dl |
p-value: 0.419195% CI: [-0.56, 0.23]Mixed Models Analysis
Secondary
Nicotine Exposure
Measured by cotinine (ng/ml) measured in plasma
Time frame: 18 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Nicotine Exposure | 128.6 ng/ml |
| Same Nicotine Content Cigarettes | Nicotine Exposure | 265.3 ng/ml |
p-value: <0.000195% CI: [-171.7, -101.7]Mixed Models Analysis
Secondary
Perceived Stress
Perceived Stress is measured via the Perceived Stress Scale Score. The 10-item version was used. Scale range is 0-40. Higher scores indicate more stress.
Time frame: 18 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Perceived Stress | 12.9 score on a scale |
| Same Nicotine Content Cigarettes | Perceived Stress | 11.1 score on a scale |
p-value: 0.020795% CI: [0.28, 3.33]Mixed Models Analysis
Secondary
Predictors of Participant Dropout
Baseline participant characteristics were evaluated for their association with the primary outcome, randomized trial phase dropout. The table below reports the number of participants who dropped out by each characteristic that was found to be univariately associated with the primary outcome.
Time frame: 18 weeks
Population: Participants (who were randomized) are stratified according to the listed characteristics.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Reduced Nicotine Content Group | 52 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Same Nicotine Content Group | 19 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Age group 18-29 | 20 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Age group 30-39 | 14 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Age group 40-49 | 15 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Age group 50-59 | 18 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Age group 60-65 | 4 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Not currently working | 31 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | Currently working | 40 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | BMI Underweight (<18.5) | 6 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | BMI Normal weight (>=18.5 and <25) | 17 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | BMI Overweight (>=25 and <30) | 15 Participants |
| Reduced Nicotine Content Cigarettes | Predictors of Participant Dropout | BMI Obese (>=30) | 33 Participants |
Comparison: The reference group is Same Nicotine Content Group.p-value: <0.000195% CI: [1.99, 5.81]Regression, Cox
Comparison: The reference group is Age equals 18-29.p-value: 0.0695% CI: [0.26, 1.03]Regression, Cox
Comparison: The reference group is Age equals 18-29.p-value: <0.00295% CI: [0.17, 0.66]Regression, Cox
Comparison: The reference group is Age equals 18-29.p-value: <0.00295% CI: [0.16, 0.65]Regression, Cox
Comparison: The reference group is Age equals 18-29.p-value: 0.195% CI: [0.13, 1.18]Regression, Cox
Comparison: The reference group is not currently working.p-value: 0.195% CI: [0.92, 2.66]Regression, Cox
Comparison: The reference group is BMI Underweight (\<18.5)p-value: 0.00695% CI: [0.1, 0.67]Regression, Cox
Comparison: The reference group is BMI Underweight group (\<18.5)p-value: 0.03495% CI: [0.13, 0.92]Regression, Cox
Comparison: The reference group is BMI Underweight group (\<18.5)p-value: 0.01195% CI: [0.13, 0.77]Regression, Cox
Secondary
Smoke Exposure
Measured in carbon monoxide levels by expired CO
Time frame: 18 weeks
Population: All randomized participants
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reduced Nicotine Content Cigarettes | Smoke Exposure | 27.2 parts per million (ppm) |
| Same Nicotine Content Cigarettes | Smoke Exposure | 31.2 parts per million (ppm) |
p-value: 0.030595% CI: [-7.68, -0.38]Mixed Models Analysis