Nicotine Dependence, Tobacco Smoking
Conditions
Keywords
Reduced nicotine cigarettes, Alternative nicotine products, Biomarkers of tobacco exposure
Brief summary
This project will examine the impact of very low nicotine content (VLNC) cigarettes in a complex tobacco and nicotine product marketplace. We will compare the number of cigarettes smoked and cigarette-free days in an experimental marketplace that contains VLNC cigarettes versus normal nicotine content (NNC) cigarettes.
Detailed description
This randomized, open label, controlled, multi-site study will simulate a real world tobacco environment by providing participants access to an experimental marketplace where they will be given vouchers for a specified number of points that can be exchanged for study cigarettes (varying in nicotine content described below) and non-combusted tobacco/nicotine products (smokeless tobacco, snus, electronic cigarette, medicinal nicotine replacement) and at the end of the study can exchange unspent points for money. Subjects (N=200 in each group) will be randomly assigned to: 1) very low nicotine content cigarettes (VLNC; 0.4 mg nicotine/g tobacco) along with non-combusted tobacco/nicotine products or 2) normal nicotine content cigarettes (NNC; 15.8 mg nicotine/g tobacco) along with non-combusted tobacco/nicotine products. Smokers will undergo an orientation visit for screening and then enter a three phase experimental trial: 1. Phase 1 - Baseline: Two week baseline assessment period during usual brand cigarette smoking. 2. Phase 2 - Marketplace Adaptation: Two week period where subjects have access to the marketplace that provides their preferred usual brand cigarettes and selected non-combusted tobacco products to allow the subject to adjust to the marketplace prior to randomization; 3. Phase 3 - Intervention: Randomization to a marketplace with access to either VLNC or NNC cigarettes plus non-combusted products for a 12 week period. Biomarker samples are collected at baseline, end of Phase 2 and end of week Phase 3 (week 12).
Interventions
0.4 mg nicotine/g tobacco; 9 mg tar
15.8 mg nicotine/g tobacco; 9 mg tar
Sponsors
Duke University
University of California, San Francisco
Wake Forest University
University of Pennsylvania
Brown University
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Phase III randomized, open label, multi-center study that will examine the impact of very low nicotine content (VLNC) cigarettes using an experimental marketplace that contains tobacco and nicotine products, simulating a real world environment. There are three phases: Phase 1 is smoking usual brand cigarettes. Phase 2 is access to a marketplace with usual brand cigarettes and other non-combusted nicotine and tobacco products. Phase 3 involves access to a marketplace with study cigarettes and other non-combusted nicotine and tobacco products.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Male or female; 2. 18/21 (legal age to purchase tobacco at site); 3. Biochemically confirmed smoker.
Exclusion criteria
1. Unstable health condition; 2. Unstable medications; 3. Pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Per Day (CPD) | 7 days prior to week 12 visit | The mean cigarettes (study and non-study cigarettes) smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes). |
| Number of Smoke-free Days | day 1 of study until day before week 12 visit | Rate of smoke-free days, defined as no cigarettes smoked in the past 24 hours calculated as the proportion of smoke-free days out of the total number of days in Phase 3. Number of smoke free days based on the interactive voice response (IVR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA) | The last visit in Phase 2 is the end of the baseline | Change in CEMA (biomarker for the mercapturic acid acrylonitrile) from end of Phase 2 (experimental marketplace with usual brand cigarettes) to end of Phase 3 (experimental marketplace with study cigarettes). |
| Study Cigarettes Per Day | 12 weeks (Phase 3) on study cigarettes | The mean study cigarettes smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes). |
| Seven Day Point-prevalence CO-verified Abstinence | 7 days before week 12 visit | Total cigarettes per day equal to 0 for all 7 days before the week 12 visit and carbon monoxide (CO) ≤ 6ppm at week 12. |
Countries
United States
Participant flow
Pre-assignment details
799 potential participants were consented and attended the screening visit. 535 eligible participants entered Phase 1; 491 continued on to Phase 2; 438 were randomized into Phase 3. See description of Phases under Study Description.
Participants by arm
| Arm | Count |
|---|---|
| Very Low Nicotine Content Cigarettes Very low nicotine content cigarettes: 0.4 mg nicotine/g tobacco; 9 mg of tar | 220 |
| Normal Nicotine Content Cigarettes Normal (Conventional) Nicotine Content: 15.8 mg nicotine/g tobacco; 9 mg of tar | 218 |
| Total | 438 |
Baseline characteristics
| Characteristic | Very Low Nicotine Content Cigarettes | Normal Nicotine Content Cigarettes | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 9 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 212 Participants | 209 Participants | 421 Participants |
| Cigarettes Per Day (CPD) | 15.6 Number of Cigarettes Per Day STANDARD_DEVIATION 6.9 | 15.5 Number of Cigarettes Per Day STANDARD_DEVIATION 7.6 | 15.5 Number of Cigarettes Per Day STANDARD_DEVIATION 7.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 4 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 54 Participants | 99 Participants |
| Race (NIH/OMB) More than one race | 21 Participants | 13 Participants | 34 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 143 Participants | 139 Participants | 282 Participants |
| Sex: Female, Male Female | 123 Participants | 102 Participants | 225 Participants |
| Sex: Female, Male Male | 97 Participants | 116 Participants | 213 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 220 | 0 / 218 |
| other Total, other adverse events | 39 / 220 | 42 / 218 |
| serious Total, serious adverse events | 7 / 220 | 6 / 218 |
Outcome results
Primary
Cigarettes Per Day (CPD)
The mean cigarettes (study and non-study cigarettes) smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).
Time frame: 7 days prior to week 12 visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Cigarettes Per Day (CPD) | 7.05 cigarettes per day | Standard Deviation 7.88 |
| Normal Nicotine Content Cigarettes | Cigarettes Per Day (CPD) | 12.95 cigarettes per day | Standard Deviation 9.07 |
Primary
Number of Smoke-free Days
Rate of smoke-free days, defined as no cigarettes smoked in the past 24 hours calculated as the proportion of smoke-free days out of the total number of days in Phase 3. Number of smoke free days based on the interactive voice response (IVR)
Time frame: day 1 of study until day before week 12 visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Number of Smoke-free Days | 18.6 days | Standard Deviation 28 |
| Normal Nicotine Content Cigarettes | Number of Smoke-free Days | 5.1 days | Standard Deviation 13.8 |
Secondary
Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA)
Change in CEMA (biomarker for the mercapturic acid acrylonitrile) from end of Phase 2 (experimental marketplace with usual brand cigarettes) to end of Phase 3 (experimental marketplace with study cigarettes).
Time frame: The last visit in Phase 2 is the end of the baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA) | -34 percentage of change |
| Normal Nicotine Content Cigarettes | Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA) | 8 percentage of change |
Secondary
Seven Day Point-prevalence CO-verified Abstinence
Total cigarettes per day equal to 0 for all 7 days before the week 12 visit and carbon monoxide (CO) ≤ 6ppm at week 12.
Time frame: 7 days before week 12 visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Very Low Nicotine Content Cigarettes | Seven Day Point-prevalence CO-verified Abstinence | 41 Participants |
| Normal Nicotine Content Cigarettes | Seven Day Point-prevalence CO-verified Abstinence | 15 Participants |
Secondary
Study Cigarettes Per Day
The mean study cigarettes smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).
Time frame: 12 weeks (Phase 3) on study cigarettes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Study Cigarettes Per Day | 5.33 cigarettes per day | Standard Deviation 6.86 |
| Normal Nicotine Content Cigarettes | Study Cigarettes Per Day | 12.42 cigarettes per day | Standard Deviation 9.23 |