Cigarette Smoking-Related Carcinoma, Tobacco-Related Carcinoma
Conditions
Brief summary
This trial studies what would happen if the nicotine levels in cigarettes are greatly reduced, but electronic cigarettes containing different amount of nicotine are available. Different levels of nicotine may effect certain behaviors, including withdrawal symptoms, nicotine cravings, and mood and may lead to changes in smoking behavior in current daily and intermittent smokers..
Detailed description
PRIMARY OBJECTIVES: I. To characterize the effects of switching to VLNCCs plus ECIG-Hi or ECIG-Lo nicotine doses on abuse liability among daily and intermittent smokers. EXPLORATORY OBJECTIVES: I. To explore the effects of switching to VLNCCs plus ECIG-Hi or ECIG-Lo nicotine doses on abuse liability using biochemical measures of product use, compensation, and toxicant exposure, and self-reported measures of withdrawal, craving, affect, and satisfaction. II. To explore the effects of switching from usual-brand cigarettes to VLNCCs, and from VLNCCs to VLNCC+ECIGs on measures of abuse liability. III. To characterize the effects of dual use of VLNCC and JUUL ECIGs on abuse liability. OUTLINE: PHASE I: Patients smoke their usual cigarettes brand during week 1. PHASE II: Patients smoke VLNCC cigarettes provided during weeks 2-4. PHASES III-IV: Patients are randomized to 1 of 2 arms. ARM I: Patients smoke ECIG-high (Hi) for 3 weeks and then ECIG-low (Lo) for 3 weeks ARM II: Patients smoke ECIG-Lo for 3 weeks and then ECIG-Hi for 3 weeks. After completion of study, patients are followed up for 30 days.
Interventions
DRUGCigarette
Smoke usual brand of cigarettes
Received NRT (Electronic Cigarette - ECIG-Hi)
OTHERQuestionnaire Administration
Ancillary studies
OTHERSurvey Administration
Ancillary studies
DRUGVery Low Nicotine Content Cigarette
Smoke very low nicotine content cigarette
DEVICEECIG-Hi
Patients smoke ECIG-Hi for 3 weeks and then ECIG-Lo for 3 weeks.
DEVICEECIG-Lo
Patients smoke ECIG-Lo for 3 weeks and then ECIG-Hi for 3 weeks
Sponsors
National Institute on Drug Abuse (NIDA)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Sign consent and agree to all study procedures * Have an address where he/she can receive mail * Have a device available to conduct telehealth visit (e.g., smartphone, computer, tablet, internet access, etc.) * Able to follow verbal and written instructions in English * Willing and able to complete two spirometry sessions (this criterion waived during COVID-19 pandemic) * Be the only participant in their household * Interested in trying novel nicotine products * Daily smokers: \>= 1 cigarette/little cigar per day * Intermittent smokers: \>= 1 cigarette/little cigar per day 4 to 27 days per month * Agrees to comply with all MD Anderson institutional policies related to COVID-19 screening prior to each in-person research visit * The individual agrees to not engage in study procedures or interactions with study personnel while operating a vehicle
Exclusion criteria
* Unwilling to refrain from other e-cigarette use for the duration of the study, other than what is provided to them for study purposes * Current/recent use of certain medications: * Smoking cessation meds (past 90 days; e.g., wellbutrin, bupropion, Zyban, nicotine replacement therapy \[NRT\], Chantix) * Certain medications to treat depression (last 14 days; e.g., amitriptyline) * A case by case determination will be made by study physician for medication on the precautionary list, (e.g. nitroglycerin) * Self-reported daily use of opioids for 30 days or more on phone screen or at screening is exclusionary however pro re nata (PRN) use is allowed (e.g., 3 to 7 days per week or less or if more frequent, use less than a month's duration * Unstable medical condition as determined by the medical team * Self-reported bronchial or respiratory infection in the last 14 days (this criterion waived during COVID-19 pandemic) * Subject's spirometry forced expiratory volume in 1 second (FEV1) percentage reading is \< 50 (severe to very severe obstruction) (this criterion waived during COVID-19 pandemic) * Self-reported abnormal heart rhythms or cardiovascular disease (stroke, chest pain, heart attack) in the last 3 months * Meet criteria for major depressive syndrome or suicidality on the Patient Health Questionnaire-9 (PHQ-9) * Self report of past or current diagnosis of bi-polar disorder or schizophrenia/schizoaffective disorder * Self-reported other tobacco use besides cigarettes or little cigars (e.g., hookah, cigarillos, smokeless tobacco, chewing tobacco, pipes, cigars, etc.) on 10 or more days in the last month * Recent (past 90 days), current, or planned (within the next 45 days) involvement in smoking cessation activities * Positive urine pregnancy test at screening. Women who are two years post-menopausal, or who have had a tubal ligation or a partial or full hysterectomy will not be subject to a urine pregnancy test * Women that are breastfeeding or of childbearing potential and not protected by a medically acceptable, effective method of birth control while enrolled in the study. Medically acceptable contraceptives include: * Approved hormonal contraceptives (such as birth control pills, patches, implants or injections) * Barrier methods (such as condom or diaphragm) used with a spermicide, or * An intrauterine device (IUD) * Contraceptives sold for emergency use after unprotected sex are not acceptable methods for routine use * Subject considered by the investigator to be unsuitable to participate in the study (e.g., due to cognitive deficits or instability to last the entire duration of the study)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Usual Brand Cigarettes Per Day | One to three weeks | Mean usual brand cigarettes per day (CPD) smoked during the phase |
| Very Low Nicotine Content Cigarettes Per Day | One to three weeks | Mean very low nicotine content cigarettes per day (CPD) smoked during the phase |
| Total Nicotine Equivalents (TNE) | One to three weeks | Geometric means of the natural log of total nicotine equivalents (TNE), calculated as the sum of total nicotine, total cotinine, total 3'-hydroxycotinine and nicotine N-oxide excreted in urine |
Countries
United States
Participant flow
Recruitment details
Participants were adults residing in the Houston metropolitan area
Pre-assignment details
Overall, 1129 individuals were screened for interest and eligibility. Of those screened, 461 were ineligible and 455 declined to participate. A total of 213 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| eGo Arm Participants enrolled in the eGo Arm of this crossover design trial | 176 |
| JUUL Arm Participants enrolled in the JUUL Arm of this crossover design trial | 37 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Phase 2 (Weeks 2-4) | Lost to Follow-up | 0 | 7 | 0 | 0 | 0 | 2 | 0 | 0 |
| Phase 2 (Weeks 2-4) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 12 | 0 | 0 |
| Phase 2 (Weeks 2-4) | Withdrawal by Subject | 0 | 11 | 0 | 0 | 0 | 1 | 0 | 0 |
| Phase 3 (Weeks 5-7) | Lost to Follow-up | 0 | 0 | 3 | 2 | 0 | 0 | 1 | 0 |
| Phase 3 (Weeks 5-7) | Withdrawal by Subject | 0 | 0 | 3 | 5 | 0 | 0 | 0 | 3 |
| Phase 4 (Weeks 8-10) | Lost to Follow-up | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Phase 4 (Weeks 8-10) | Withdrawal by Subject | 0 | 0 | 3 | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | eGo Arm | Total | JUUL Arm |
|---|---|---|---|
| Age, Continuous | 41.34 years STANDARD_DEVIATION 11.95 | 41.74 years STANDARD_DEVIATION 11.84 | 43.65 years STANDARD_DEVIATION 11.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 19 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 159 Participants | 194 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 77 Participants | 88 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants | 21 Participants | 2 Participants |
| Race (NIH/OMB) White | 75 Participants | 95 Participants | 20 Participants |
| Region of Enrollment United States | 176 participants | 213 participants | 37 participants |
| Sex: Female, Male Female | 80 Participants | 96 Participants | 16 Participants |
| Sex: Female, Male Male | 96 Participants | 117 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 176 | 0 / 176 | 0 / 151 | 0 / 152 | 0 / 37 | 0 / 37 | 0 / 19 | 0 / 21 |
| other Total, other adverse events | 16 / 176 | 52 / 176 | 23 / 151 | 18 / 152 | 2 / 37 | 1 / 37 | 1 / 19 | 1 / 21 |
| serious Total, serious adverse events | 0 / 176 | 3 / 176 | 1 / 151 | 0 / 152 | 0 / 37 | 0 / 37 | 0 / 19 | 0 / 21 |
Outcome results
Primary
Total Nicotine Equivalents (TNE)
Geometric means of the natural log of total nicotine equivalents (TNE), calculated as the sum of total nicotine, total cotinine, total 3'-hydroxycotinine and nicotine N-oxide excreted in urine
Time frame: One to three weeks
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Usual Brand Cigarette Phase (eGo Arm) | Total Nicotine Equivalents (TNE) | 25.621411 ln(nmol/mL) |
| Very Low Nicotine Content Cigarette (VLNCC) Phase (eGo Arm) | Total Nicotine Equivalents (TNE) | 5.37663 ln(nmol/mL) |
| VLNCCs + Low-dose Electronic Cigarettes Phase (eGo Arm) | Total Nicotine Equivalents (TNE) | 8.418756 ln(nmol/mL) |
| VLNCCs + High-dose Electronic Cigarettes Phase (eGo Arm) | Total Nicotine Equivalents (TNE) | 11.388661 ln(nmol/mL) |
| Usual Brand Cigarette Phase (JUUL Arm) | Total Nicotine Equivalents (TNE) | 35.052048 ln(nmol/mL) |
| Very Low Nicotine Content Cigarette (VLNCC) Phase (JUUL Arm) | Total Nicotine Equivalents (TNE) | 5.414214 ln(nmol/mL) |
| VLNCCs + Low-dose Electronic Cigarettes Phase (JUUL Arm) | Total Nicotine Equivalents (TNE) | 23.83952 ln(nmol/mL) |
| VLNCCs + High-dose Electronic Cigarettes Phase (JUUL Arm) | Total Nicotine Equivalents (TNE) | 32.428008 ln(nmol/mL) |
Primary
Usual Brand Cigarettes Per Day
Mean usual brand cigarettes per day (CPD) smoked during the phase
Time frame: One to three weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Usual Brand Cigarette Phase (eGo Arm) | Usual Brand Cigarettes Per Day | 15.803 Cigarettes per Day | Standard Error 0.5304 |
| Very Low Nicotine Content Cigarette (VLNCC) Phase (eGo Arm) | Usual Brand Cigarettes Per Day | 2.1563 Cigarettes per Day | Standard Error 0.5427 |
| VLNCCs + Low-dose Electronic Cigarettes Phase (eGo Arm) | Usual Brand Cigarettes Per Day | 1.8353 Cigarettes per Day | Standard Error 0.5807 |
| VLNCCs + High-dose Electronic Cigarettes Phase (eGo Arm) | Usual Brand Cigarettes Per Day | 1.4931 Cigarettes per Day | Standard Error 0.5751 |
| Usual Brand Cigarette Phase (JUUL Arm) | Usual Brand Cigarettes Per Day | 12.6171 Cigarettes per Day | Standard Error 0.9155 |
| Very Low Nicotine Content Cigarette (VLNCC) Phase (JUUL Arm) | Usual Brand Cigarettes Per Day | 2.6665 Cigarettes per Day | Standard Error 0.9258 |
| VLNCCs + Low-dose Electronic Cigarettes Phase (JUUL Arm) | Usual Brand Cigarettes Per Day | 2.3042 Cigarettes per Day | Standard Error 1.219 |
| VLNCCs + High-dose Electronic Cigarettes Phase (JUUL Arm) | Usual Brand Cigarettes Per Day | 2.1429 Cigarettes per Day | Standard Error 1.146 |
Primary
Very Low Nicotine Content Cigarettes Per Day
Mean very low nicotine content cigarettes per day (CPD) smoked during the phase
Time frame: One to three weeks
Population: Participants were not provided with very low nicotine content cigarettes during the Usual Brand Cigarette Phase (Phase 1)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarette (VLNCC) Phase (eGo Arm) | Very Low Nicotine Content Cigarettes Per Day | 15.7421 Cigarettes per Day | Standard Error 0.9071 |
| VLNCCs + Low-dose Electronic Cigarettes Phase (eGo Arm) | Very Low Nicotine Content Cigarettes Per Day | 10.2652 Cigarettes per Day | Standard Error 0.932 |
| VLNCCs + High-dose Electronic Cigarettes Phase (eGo Arm) | Very Low Nicotine Content Cigarettes Per Day | 10.5811 Cigarettes per Day | Standard Error 0.9285 |
| Very Low Nicotine Content Cigarette (VLNCC) Phase (JUUL Arm) | Very Low Nicotine Content Cigarettes Per Day | 12.8014 Cigarettes per Day | Standard Error 1.6928 |
| VLNCCs + Low-dose Electronic Cigarettes Phase (JUUL Arm) | Very Low Nicotine Content Cigarettes Per Day | 6.5151 Cigarettes per Day | Standard Error 2.0882 |
| VLNCCs + High-dose Electronic Cigarettes Phase (JUUL Arm) | Very Low Nicotine Content Cigarettes Per Day | 6.2979 Cigarettes per Day | Standard Error 1.9709 |