An interventional study of Cigarette Smoking and Cigarette Smoking in Cigarette Smoking-Related Carcinoma, sponsored by Ohio State University Comprehensive Cancer Center. Completed at 1 site in United States. Open to participants aged 21 Years to 50 Years. Per ClinicalTrials.gov, last updated 2025-03-24.
Sponsored by Ohio State University Comprehensive Cancer Center · Not applicable, Interventional, and Prevention
This clinical trial studies the effect of free-base compared with nicotine salt based e-liquids on electronic cigarette (EC) puffing behavior, abuse liability, and deposition and absorption of nicotine in the respiratory tract and rate of uptake in the brain in current EC smokers. The results from this study may provide much needed scientific information to public health officials and regulators.
PRIMARY OBJECTIVES:
I. To examine the influence of nicotine form on puffing behavior and abuse liability.
II. To evaluate the influence of nicotine form and concentration on nicotine distribution in the brain and respiratory tract.
OUTLINE:
VISIT 1: Patients sample 4-liquids to determine whether they can vape the unflavored e-liquid without coughing
Patients are randomized to 1 of 2 arms.
ARM I:
VISIT 2: Patients receive 1 puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 minutes (min) head and 5 min chest positron emission tomography (PET)/computed tomography (CT) and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest PET/CT.
VISIT 3: Patients receive 1 puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min head and 5 min chest PET/CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest
ARM II:
VISIT 2: Patients receive 1 puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min head and 5 min chest PET/CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest.
VISIT 3: Patients receive 1 puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min head and 5 min chest PET/CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest PET/CT.
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Exclusion Criteria:
VISIT 2: Patients receive 1 puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min head and 5 min chest PET?CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest PET/CT. VISIT 3: Patients receive 1 puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min head and 5 min chest PET/CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest
Behavioral: Cigarette Smoking · Procedure: Computed Tomography · Procedure: Positron Emission Tomography · Other: Questionnaire Administration
VISIT 2: Patients receive 1 puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min head and 5 min chest PET/CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored unprotonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest. VISIT 3: Patients receive 1 puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min head and 5 min chest PET/CT and then 0-15 min chest and 5 min head PET/CT. About 2 hours post initial PET/CT, patients receive a second puff of tobacco flavored or unflavored protonated e-liquid and undergo 0-15 min chest and 5 min head PET/CT and then 0-15 min head and 5 min chest PET/CT.
Behavioral: Cigarette Smoking · Procedure: Computed Tomography · Procedure: Positron Emission Tomography · Other: Questionnaire Administration
Receive 1 puff of tobacco flavored protonated e-liquid
Receive 1 puff of unflavored protonated e-liquid
Receive 1 puff of tobacco flavored unprotonated cigarette
Receive 1 puff of unfavored unprotonated cigarette
Undergo PET/CT
Also known as: CAT, CAT Scan, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography
Undergo PET/CT
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging
Ancillary studies
PET/CT Imaging of the Head
Evaluate effect of nicotine form (free-base vs nicotine salt base) on nicotine absorption and distribution in the brain with total absorbed dose (TAD) of \[11C\]nicotine.
Time frame: 1.5 hours
PET/CT Imaging of the Chest
Evaluate effect of nicotine form (free-base vs nicotine salt base) on nicotine absorption and distribution in the respiratory tract with total absorbed dose (TAD) of \[11C\]nicotine.
Time frame: 1.5 hours
Puff Volume (mL)
Puffing topography data was captured by the study e-cigarette to determine the puff volume.
Time frame: approx. 30 minutes
Puff Duration (s)
Puffing topography data was captured by the study e-cigarette to determine the puff duration.
Time frame: approx. 30 minutes
Age of First Tobacco Use
Age of first use will be assessed using the tobacco use history questionnaire.
Time frame: approx. 5 minutes
Years of Tobacco Use
Years of tobacco use will be assessed using the tobacco use history questionnaire.
Time frame: approx. 5 minutes
Years of Regular Use of Nicotine/Tobacco Products
Years of regular use of nicotine/tobacco products will be assessed using the tobacco history questionnaire
Time frame: approx. 5 minutes
Past 30 Day Use of Nicotine/Tobacco Products
Days used in the past 30 days of nicotine/tobacco products including cigars, cigarillos, little cigars, pipe tobacco, chewing tobacco, snuff, snus, EC/vape/mod/APV/e-hookah, and hookah tobacco.
Time frame: approx. 5 minutes
Modified Cigarette Evaluation Questionnaire (mCEQ)
12-item modified Cigarette Evaluation Questionnaire (mCEQ) completed following e-cigarette self-administration to assess subjective responses. The 12-item mCEQ includes five subscales: Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations, and Craving Reduction, with items rated from 0 (not at all) to 6 (extremely likely). Scores for each subscale are calculated as the mean of the individual item responses or the single item. Higher scores indicate greater intensity on that scale.
Time frame: approx. 5 minutes
Drug Effects Liking Questionnaire (DEQ)
An adapted version of the Drug Effects/Liking Questionnaire will assess the desire and liking of the study products. Five visual analog scale items ranging from 0 (not at all) to 100 (extremely) assessed wanting to vape the product again, liking the product, enjoying the product, finding the product pleasurable and satisfying. Higher scores indicate greater liking.
Time frame: approx. 5 minutes
Modified Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form (QSU)
Urges/craving will be measured using a modified version of the Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form. This is a 10-item measure where participants rate e-cigarette smoking-related items (All I want right now is an e-cigarette) on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Similar to previous studies, we will collapse the items into two previously identified factors (Factor 1: strong desire and intention to smoke an e-cigarette; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 35 with higher scores indicating greater craving to vape.
Time frame: aprox. 5 minutes
Minnesota Nicotine Withdrawal Scale
Nicotine withdrawal will be assessed using the empirically validated 15-item version of the Minnesota Nicotine Withdrawal Scale (MNWS). Items were rated on a 5-point scale from 0 (none) to 4 (severe). This measure assesses smoking craving, anger/irritability, anxiety, depressed mood, restlessness/difficulty concentrating, increased appetite, sleep problems, and somatic symptoms (nausea, constipation, sore throat, dizziness, coughing). MNWS is the sum of 8 items with scores ranging from 0 to 32 and MNWS Craving is a single item with scores ranging from 0 to 4, higher scores indicate a greater craving.
Time frame: approx. 5 minutes
Exhaled Breath Carbon Monoxide (CO)
Exhaled breath carbon monoxide was collected before each scan with a handheld electrochemical device.
Time frame: approx. 5 minutes
| Milestone | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) |
|---|---|---|
| Started | 12 | 8 |
| Sample protonated e-liquid | 12 | 8 |
| Sample unprotonated e-liquid | 12 | 8 |
| Completed | 12 | 8 |
| Not completed | 0 | 0 |
Evaluate effect of nicotine form (free-base vs nicotine salt base) on nicotine absorption and distribution in the brain with total absorbed dose (TAD) of \[11C\]nicotine.
| %TAD/kg | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| PET/CT Imaging of the Head | 2.81 ± 0.92 | 2.40 ± 0.62 |
Evaluate effect of nicotine form (free-base vs nicotine salt base) on nicotine absorption and distribution in the respiratory tract with total absorbed dose (TAD) of \[11C\]nicotine.
| %TAD/kg | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Upper Respiratory Tract | 6.18 ± 2.17 | 11.62 ± 3.17 |
| Lower Respiratory Tract | 10.35 ± 3.49 | 5.53 ± 0.81 |
Puffing topography data was captured by the study e-cigarette to determine the puff volume.
| mL | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Puff Volume (mL) | 79.35 ± 72.75 | 73.76 ± 70.82 |
Puffing topography data was captured by the study e-cigarette to determine the puff duration.
| seconds | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Puff Duration (s) | 2.87 ± 1.43 | 2.82 ± 1.61 |
Age of first use will be assessed using the tobacco use history questionnaire.
| years | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) |
|---|---|---|
| Age of First Tobacco Use | 14.58 ± 2.02 | 14.63 ± 1.60 |
Years of tobacco use will be assessed using the tobacco use history questionnaire.
| years | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) |
|---|---|---|
| Years of Tobacco Use | 19.58 ± 8.85 | 16.88 ± 6.75 |
Years of regular use of nicotine/tobacco products will be assessed using the tobacco history questionnaire
| years | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) |
|---|---|---|
| Years of Regular Use of Nicotine/Tobacco Products | 16.83 ± 8.99 | 15.13 ± 6.90 |
Days used in the past 30 days of nicotine/tobacco products including cigars, cigarillos, little cigars, pipe tobacco, chewing tobacco, snuff, snus, EC/vape/mod/APV/e-hookah, and hookah tobacco.
| days | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) |
|---|---|---|
| Cigarettes | 0 ± 0 | 0.75 ± 2.12 |
| Pipes | 0 ± 0 | 0 ± 0 |
| Cigars | 0 ± 0 | 0 ± 0 |
| Cigarillos | 0 ± 0 | 0 ± 0 |
| Little Cigars | 0 ± 0 | 0 ± 0 |
| e-cigarettes | 29.83 ± 0.58 | 30.00 ± 0 |
| Smokeless Tobacco | 0 ± 0 | 0 ± 0 |
| Snus | 0 ± 0 | 0 ± 0 |
| Hookah | 0.17 ± 0.58 | 0 ± 0 |
12-item modified Cigarette Evaluation Questionnaire (mCEQ) completed following e-cigarette self-administration to assess subjective responses. The 12-item mCEQ includes five subscales: Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations, and Craving Reduction, with items rated from 0 (not at all) to 6 (extremely likely). Scores for each subscale are calculated as the mean of the individual item responses or the single item. Higher scores indicate greater intensity on that scale.
| Score on a scale | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Satisfaction | 2.28 ± 1.31 | 1.42 ± 0.92 |
| Psychological Reward | 2.17 ± 1.27 | 1.38 ± 0.93 |
| Aversion | 0.88 ± 1.05 | 0.94 ± 1.47 |
| Enjoyment of Respiratory Tract Sensations | 2.42 ± 1.31 | 1.25 ± 1.16 |
| Craving Reduction | 3.67 ± 2.10 | 3.25 ± 1.83 |
An adapted version of the Drug Effects/Liking Questionnaire will assess the desire and liking of the study products. Five visual analog scale items ranging from 0 (not at all) to 100 (extremely) assessed wanting to vape the product again, liking the product, enjoying the product, finding the product pleasurable and satisfying. Higher scores indicate greater liking.
| units on a scale | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Want | 60.08 ± 29.44 | 42.88 ± 26.69 |
| Like | 51.25 ± 32.76 | 32.50 ± 25.93 |
| Enjoy | 57.25 ± 30.63 | 31.88 ± 26.38 |
| Pleasurable | 56.08 ± 32.42 | 29.13 ± 26.94 |
| Satisfying | 60.33 ± 32.66 | 35.63 ± 28.54 |
Urges/craving will be measured using a modified version of the Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form. This is a 10-item measure where participants rate e-cigarette smoking-related items (All I want right now is an e-cigarette) on a 7-point Likert scale ranging from 1 (strongly disagree) to 7 (strongly agree). Similar to previous studies, we will collapse the items into two previously identified factors (Factor 1: strong desire and intention to smoke an e-cigarette; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 35 with higher scores indicating greater craving to vape.
| Score on a scale | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Desire | 29.45 ± 6.83 | 30.15 ± 5.82 |
| Relief | 16.35 ± 8.01 | 17.40 ± 9.38 |
Nicotine withdrawal will be assessed using the empirically validated 15-item version of the Minnesota Nicotine Withdrawal Scale (MNWS). Items were rated on a 5-point scale from 0 (none) to 4 (severe). This measure assesses smoking craving, anger/irritability, anxiety, depressed mood, restlessness/difficulty concentrating, increased appetite, sleep problems, and somatic symptoms (nausea, constipation, sore throat, dizziness, coughing). MNWS is the sum of 8 items with scores ranging from 0 to 32 and MNWS Craving is a single item with scores ranging from 0 to 4, higher scores indicate a greater craving.
| score on a scale | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| MNWS | 9.50 ± 7.38 | 9.10 ± 6.32 |
| MNWS Craving | 2.60 ± 0.94 | 2.70 ± 1.17 |
Exhaled breath carbon monoxide was collected before each scan with a handheld electrochemical device.
| ppm | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| Exhaled Breath Carbon Monoxide (CO) | 2.45 ± 1.79 | 2.80 ± 2.31 |
Collected over Over 3 study visits, up to 3 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Protonated E-liquid | 0/20 (0%) | 0/20 (0%) | 2/20 (10%) |
| Unprotonated E-liquid | 0/20 (0%) | 0/20 (0%) | 0/20 (0%) |
| Event | Protonated E-liquid | Unprotonated E-liquid |
|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 2/20 | 0/20 |
| Age, Continuous(years) | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) | Total |
|---|---|---|---|
| Mean | 34.17 ± 7.91 | 31.50 ± 7.27 | 33.10 ± 7.58 |
| Sex: Female, Male(Participants) | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) | Total |
|---|---|---|---|
| Female | 7 | 4 | 11 |
| Male | 5 | 4 | 9 |
| Race/Ethnicity, Customized(Participants) | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 12 | 6 | 18 |
| Middle Eastern | 0 | 1 | 1 |
| More than one race | 0 | 1 | 1 |
| Years of regular e-cigarette use(years) | Arm I (Protonated E-liquid, Unprotonated E-liquid) | Arm II (Unprotonated E-liquid, Protonated E-liquid) | Total |
|---|---|---|---|
| Mean | 3.67 ± 2.84 | 4.13 ± 2.95 | 3.85 ± 2.81 |
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Ohio State University Comprehensive Cancer Center