Tobacco Dependence
Conditions
Keywords
smoking, electronic cigarettes, nicotine, ecig
Brief summary
The overall goal of this project is to understand the likely health effects of cigarette smokers switching to a Standardized Research Electronic Cigarette (SREC) and to assess the role of nicotine delivery on switching and acceptability as well as markers of health outcomes. Current smokers who meet all eligibility criteria will completely switch from their combustible (regular) cigarettes to an electronic cigarette (SREC) that either contains 58 mg/ml of nicotine or 0 mg/ml of nicotine in the liquid. The investigators' hypothesis is that attempting to switch to a SREC will result in a reduction in markers of harms to health, as compared with the baseline (smoking) measures. The investigators also hypothesize that nicotine-containing SRECs will facilitate switching from smoking more efficiently than zero nicotine SRECs and will result in a significantly greater improvement in markers of health risk, but will result in higher ratings of dependence on the SREC (as compared to the zero nicotine SREC).
Detailed description
This project is a prospective parallel-group randomized double-blind, placebo-controlled study in which 104 current smokers who are willing to completely switch from their regular cigarettes to an electronic cigarette (SREC) for 6 weeks will be randomly allocated to use a SREC containing either 58 or 0 mg/ml nicotine in the liquid. Following randomization to their assigned study product, participants will be supported in their switching efforts with regular contacts both in person at the Penn State Milton S. Hershey Medical Center and over the phone. The main measures will be recorded at two in-person visits after the randomization (switching) visit: (a) 3 weeks after switching and (b) 6 weeks after switching. All participants will also be followed up at 10 weeks by phone to identify whether they have continued to use electronic cigarettes or regular cigarettes and to assess their motivation to change.
Interventions
OTHERNicotine-Containing Electronic Cigarette
The electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir (pod) and a rechargeable power supply unit. The experimental group in this project will receive a SREC device with liquid containing 58 mg/mL of nicotine.
OTHERNon-Nicotine Electronic Cigarette
The electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir (pod) and a rechargeable power supply unit. The placebo group in this project will receive a SREC device with liquid containing 0 mg/mL of nicotine.
Sponsors
National Institute on Drug Abuse (NIDA)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 21 to 70 * Smoke ≥5 cigarettes per day for at least the past 12 months * Smoke regular, filtered cigarettes or machine-rolled cigarettes with a filter * Exhaled CO measurement ≥6 ppm at baseline visit * No serious quit attempt in prior month * Willing to completely cease cigarette consumption and switch to an e-cig * Willing and able to attend regular visits over a 7-week period * Able to read and write in English * Able to understand and consent to study procedures
Exclusion criteria
* Unstable or significant medical condition such as COPD, kidney disease, or liver disease in the past 12 months * Severe immune system disorders * Women who are pregnant, trying to become pregnant, or nursing * Use of any non-cigarette nicotine delivery product in the past 7 days * Use of an e-cig for 5 or more days in the past 28 days or any use in the past 7 days * Uncontrolled mental illness or substance abuse or inpatient treatment for these conditions in the past 6 months * History of a seizure disorder or had a seizure in the past 12 months * Currently or have ever taken medications prescribed to prevent seizures (such as Carbamazepine or Phenobarbital). Using seizure medications for off-label use (indications other than treatment for seizures) will not be included as an exclusion, these will be assessed on a case-by-case basis. * History of difficulty providing or unwilling to provide blood samples (fainting, poor veins, anxiety, seizures) * Surgery requiring general anesthesia in the past 6 weeks * Use of marijuana or any illicit drug/prescription drugs for non-medical use daily/almost daily or weekly in the past 3 months per NIDA Quick Screen * Use of hand-rolled, roll your own cigarettes * Known allergy to propylene glycol or vegetable glycerin * Other member of household currently participating in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary NNAL Concentration | 6-week visit (post-treatment) | Concentration of urinary carcinogen biomarker of exposure, NNAL, corrected for creatinine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled Carbon Monoxide (CO) | 6-week visit (post-treatment) | Exhaled CO (parts per million \[ppm\]) |
| Urine Cotinine Concentration | 6-week visit (post-treatment) | Cotinine (ng/ml) will serve as a measure of exposure to nicotine. |
| Blood Pressure | 6-week visit (post-treatment) | systolic blood pressure in mm Hg |
| Fagerstrom Test for Nicotine Dependence Mean Total Score | 6-week visit (post-treatment) | Nicotine dependence for cigarettes will be assessed via the Fagerstrom Test for Nicotine Dependence (FTND), a measure with total scores ranging from 0 (very low dependence) to 10 (very high dependence). |
| Penn State Electronic Cigarette Dependence Index | 6-week visit (post-treatment) | Nicotine dependence for e-cigarettes will be assessed via the Penn State Electronic Nicotine Dependence Index, a measure with total scores ranging from 0 (very low dependence) to 20 (very high dependence). |
| Cigarettes Per Day | 6-week visit (post-treatment) | Mean number of cigarettes smoked per day based on the past 7 days |
| Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs) | 6-week visit (post-treatment) | Zero cigarettes or other tobacco products (not including e-cigs) used in the past 7 days and a CO \<6ppm |
| Pulmonary Function | 6-week visit (post-treatment) | Forced expiratory volume in one second (FEV1). |
| E-cig Use Days | 10-week visit (post-treatment) | The number of days the e-cig was used since 6-week visit (post-treatment) |
| Number of Participants With Self-reported Abstinence | 10-week visit (post-treatment) | Abstinence will be considered zero cigarettes and other tobacco products (not including e-cigs) in the past 7 days |
| Heart Rate Variability (HRV) | 6-week visit (post-treatment) | Heart Rate Variability (HRV) will be assessed from resting Holter EKG output. |
| Presence of Premature Ventricular Contractions (PVCs) | 6-week visit (post-treatment) | Presence of PVCs will be assessed from resting Holter EKG output. |
| ST-Elevation | 6-week visit (post-treatment) | ST-Elevation will be assessed from resting Holter EKG output |
| QRS Duration | 6-week visit (post-treatment) | QRS duration will be assessed from resting Holter EKG output. |
| Total Score on Minnesota Nicotine Withdrawal Scale | 1-week visit (post-treatment) | Withdrawal and craving will be assessed via the Minnesota Nicotine Withdrawal Scale. Total scores range from 0-28. Higher scores indicate worse withdrawal symptoms. |
Countries
United States
Participant flow
Pre-assignment details
One participant was excluded from the study before their assignment to a group because she did not meet the eligibility criteria for blood pressure.
Participants by arm
| Arm | Count |
|---|---|
| Nicotine-Containing Electronic Cigarette The experimental group will be provided with and encouraged to use a Standardized Research Electronic Cigarette (SREC) with liquid containing 58 mg/ml nicotine for the duration of 6 weeks.
Nicotine-Containing Electronic Cigarette: The electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir (pod) and a rechargeable power supply unit. The experimental group in this project will receive a SREC device with liquid containing 58 mg/mL of nicotine. | 52 |
| Non-Nicotine Electronic Cigarette The placebo group will be provided with and encouraged to use a Standardized Research Electronic Cigarette (SREC) with liquid containing 0 mg/ml nicotine for the duration of 6 weeks.
Non-Nicotine Electronic Cigarette: The electronic cigarette (e-cig) used in this study will be the Standardized Research Electronic Cigarette (SREC). The SREC product is a pod-based device and comprises a replaceable pre-filled liquid reservoir (pod) and a rechargeable power supply unit. The placebo group in this project will receive a SREC device with liquid containing 0 mg/mL of nicotine. | 52 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Randomization Period | Lost to Follow-up | 7 | 12 |
| Randomization Period | Withdrawal by Subject | 10 | 6 |
Baseline characteristics
| Characteristic | Nicotine-Containing Electronic Cigarette | Non-Nicotine Electronic Cigarette | Total |
|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 9.9 | 49.4 years STANDARD_DEVIATION 9.9 | 50.9 years STANDARD_DEVIATION 10 |
| Education Greater than high school | 41 Participants | 43 Participants | 84 Participants |
| Education High school or less | 11 Participants | 9 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 52 Participants | 103 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 44 Participants | 50 Participants | 94 Participants |
| Region of Enrollment United States | 52 participants | 52 participants | 104 participants |
| Sex: Female, Male Female | 35 Participants | 33 Participants | 68 Participants |
| Sex: Female, Male Male | 17 Participants | 19 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 52 |
| other Total, other adverse events | 11 / 52 | 8 / 52 |
| serious Total, serious adverse events | 1 / 52 | 0 / 52 |
Outcome results
Primary
Urinary NNAL Concentration
Concentration of urinary carcinogen biomarker of exposure, NNAL, corrected for creatinine
Time frame: 6-week visit (post-treatment)
Population: Four missing values because sample could not be analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Urinary NNAL Concentration | 151.6 ng/ml | Standard Deviation 235.1 |
| Non-Nicotine Electronic Cigarette | Urinary NNAL Concentration | 338.2 ng/ml | Standard Deviation 270.1 |
p-value: 0.0039Wilcoxon (Mann-Whitney)
Secondary
Blood Pressure
systolic blood pressure in mm Hg
Time frame: 6-week visit (post-treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Blood Pressure | 125.91 mmHg | Standard Deviation 15.74 |
| Non-Nicotine Electronic Cigarette | Blood Pressure | 124.74 mmHg | Standard Deviation 12.13 |
p-value: 0.8429Wilcoxon (Mann-Whitney)
Secondary
Cigarettes Per Day
Mean number of cigarettes smoked per day based on the past 7 days
Time frame: 10-week visit (post-treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Cigarettes Per Day | 5.03 cigarettes per day | Standard Deviation 8.04 |
| Non-Nicotine Electronic Cigarette | Cigarettes Per Day | 6.47 cigarettes per day | Standard Deviation 6.15 |
p-value: 0.1084Wilcoxon (Mann-Whitney)
Secondary
Cigarettes Per Day
Mean number of cigarettes smoked per day based on the past 7 days
Time frame: 6-week visit (post-treatment)
Population: Missing data for cigarettes per day for two participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Cigarettes Per Day | 3.78 cigarettes per day | Standard Deviation 6.75 |
| Non-Nicotine Electronic Cigarette | Cigarettes Per Day | 4.74 cigarettes per day | Standard Deviation 5.21 |
p-value: 0.043Wilcoxon (Mann-Whitney)
Secondary
E-cig Use Days
The number of days the e-cig was used since 6-week visit (post-treatment)
Time frame: 10-week visit (post-treatment)
Population: Data missing from participant six participants
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | E-cig Use Days | 6.69 days | Standard Deviation 10.57 |
| Non-Nicotine Electronic Cigarette | E-cig Use Days | 2.88 days | Standard Deviation 6.84 |
p-value: 0.3469Wilcoxon (Mann-Whitney)
Secondary
Exhaled Carbon Monoxide (CO)
Exhaled CO (parts per million \[ppm\])
Time frame: 6-week visit (post-treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Exhaled Carbon Monoxide (CO) | 10.7 ppm | Standard Deviation 18.8 |
| Non-Nicotine Electronic Cigarette | Exhaled Carbon Monoxide (CO) | 13.8 ppm | Standard Deviation 11.5 |
p-value: 0.0105Wilcoxon (Mann-Whitney)
Secondary
Fagerstrom Test for Nicotine Dependence Mean Total Score
Nicotine dependence for cigarettes will be assessed via the Fagerstrom Test for Nicotine Dependence (FTND), a measure with total scores ranging from 0 (very low dependence) to 10 (very high dependence).
Time frame: 6-week visit (post-treatment)
Population: Questionnaire was only given to participants who used cigarettes in the past 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Fagerstrom Test for Nicotine Dependence Mean Total Score | 3.69 score on a scale | Standard Deviation 2.68 |
| Non-Nicotine Electronic Cigarette | Fagerstrom Test for Nicotine Dependence Mean Total Score | 3.2 score on a scale | Standard Deviation 2.24 |
p-value: 0.4881Wilcoxon (Mann-Whitney)
Secondary
Heart Rate Variability (HRV)
Heart Rate Variability (HRV) will be assessed from resting Holter EKG output.
Time frame: 6-week visit (post-treatment)
Population: Five participants had missing data due to EKG not functioning and/or low quality data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Heart Rate Variability (HRV) | 35.2 msec | Standard Deviation 17.8 |
| Non-Nicotine Electronic Cigarette | Heart Rate Variability (HRV) | 34.6 msec | Standard Deviation 18 |
p-value: 0.589Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs)
Zero cigarettes or other tobacco products (not including e-cigs) used in the past 7 days and a CO \<6ppm
Time frame: 6-week visit (post-treatment)
Population: This is an intent-to-treat analysis so everyone who was randomized was included in the sample analyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotine-Containing Electronic Cigarette | Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs) | 19 Participants |
| Non-Nicotine Electronic Cigarette | Number of Participants With Abstinence From Cigarettes and Other Tobacco (Not Including E-cigs) | 6 Participants |
p-value: 0.0052Fisher Exact
Secondary
Number of Participants With Self-reported Abstinence
Abstinence will be considered zero cigarettes and other tobacco products (not including e-cigs) in the past 7 days
Time frame: 10-week visit (post-treatment)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotine-Containing Electronic Cigarette | Number of Participants With Self-reported Abstinence | 20 Participants |
| Non-Nicotine Electronic Cigarette | Number of Participants With Self-reported Abstinence | 10 Participants |
p-value: 0.0272Fisher Exact
Secondary
Penn State Electronic Cigarette Dependence Index
Nicotine dependence for e-cigarettes will be assessed via the Penn State Electronic Nicotine Dependence Index, a measure with total scores ranging from 0 (very low dependence) to 20 (very high dependence).
Time frame: 6-week visit (post-treatment)
Population: Questionnaire was only given to participants who used the e-cigarette in the past 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Penn State Electronic Cigarette Dependence Index | 7.21 score on a scale | Standard Deviation 3.68 |
| Non-Nicotine Electronic Cigarette | Penn State Electronic Cigarette Dependence Index | 5.45 score on a scale | Standard Deviation 3.47 |
p-value: 0.0835Wilcoxon (Mann-Whitney)
Secondary
Presence of Premature Ventricular Contractions (PVCs)
Presence of PVCs will be assessed from resting Holter EKG output.
Time frame: 6-week visit (post-treatment)
Population: Five participants had missing data due to EKG not functioning and/or low quality data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Presence of Premature Ventricular Contractions (PVCs) | 2 count of PVCs | Standard Deviation 6.8 |
| Non-Nicotine Electronic Cigarette | Presence of Premature Ventricular Contractions (PVCs) | 2.3 count of PVCs | Standard Deviation 8.4 |
p-value: 0.5448Wilcoxon (Mann-Whitney)
Secondary
Pulmonary Function
Forced expiratory volume in one second (FEV1).
Time frame: 6-week visit (post-treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Pulmonary Function | 2.7 liters | Standard Deviation 0.8 |
| Non-Nicotine Electronic Cigarette | Pulmonary Function | 2.7 liters | Standard Deviation 0.8 |
p-value: 0.8103Wilcoxon (Mann-Whitney)
Secondary
QRS Duration
QRS duration will be assessed from resting Holter EKG output.
Time frame: 6-week visit (post-treatment)
Population: Six participants had missing data due to EKG not functioning and/or low quality data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | QRS Duration | 94.3 msec | Standard Deviation 9.2 |
| Non-Nicotine Electronic Cigarette | QRS Duration | 98.3 msec | Standard Deviation 10.4 |
p-value: 0.1567Wilcoxon (Mann-Whitney)
Secondary
ST-Elevation
ST-Elevation will be assessed from resting Holter EKG output
Time frame: 6-week visit (post-treatment)
Population: Six participants had missing data due to EKG not functioning and/or low quality data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | ST-Elevation | 103.1 µV | Standard Deviation 97.2 |
| Non-Nicotine Electronic Cigarette | ST-Elevation | 87.8 µV | Standard Deviation 50.5 |
p-value: 0.65Wilcoxon (Mann-Whitney)
Secondary
Total Score on Minnesota Nicotine Withdrawal Scale
Withdrawal and craving will be assessed via the Minnesota Nicotine Withdrawal Scale. Total scores range from 0-28. Higher scores indicate worse withdrawal symptoms.
Time frame: 1-week visit (post-treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Total Score on Minnesota Nicotine Withdrawal Scale | 4.2 score on a scale | Standard Deviation 4.89 |
| Non-Nicotine Electronic Cigarette | Total Score on Minnesota Nicotine Withdrawal Scale | 6.16 score on a scale | Standard Deviation 5.89 |
p-value: 0.0797Wilcoxon (Mann-Whitney)
Secondary
Urine Cotinine Concentration
Cotinine (ng/ml) will serve as a measure of exposure to nicotine.
Time frame: 6-week visit (post-treatment)
Population: Three missing values because sample could not be analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine-Containing Electronic Cigarette | Urine Cotinine Concentration | 5295.7 ng/ml | Standard Deviation 5123.3 |
| Non-Nicotine Electronic Cigarette | Urine Cotinine Concentration | 2879.7 ng/ml | Standard Deviation 2481.5 |
p-value: 0.0182Wilcoxon (Mann-Whitney)