Free-Base Nicotine or Nicotine Salt e-Liquids in Current E-Cigarette Smokers, PeloPET Study

Not Applicable

Completed

Conditions: Cigarette Smoking-Related Carcinoma

Interventions: Behavioral: Cigarette Smoking
Procedure: Computed Tomography
Procedure: Positron Emission Tomography
Other: Questionnaire Administration

Registration Number: NCT05455086

Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

Inclusion Criteria

A current exclusive e-cigarette user (>= 1 vaping bout per day) for at least the past 6 months (confirmed by NicAlert saliva testing strip)
Between 21-50 years old
Willing to provide informed consent and abstain from all tobacco and nicotine use for at least 12 hours prior to visits 2 and 3
Willing to participate in 3 laboratory visits
Read and speak English
If utilizing study provided rideshare services, will need to live within 20 miles of Wake Forest University

Exclusion Criteria

Self-reported diagnosis of lung disease including asthma, cystic fibrosis, or chronic obstructive pulmonary disease
Unstable or significant psychiatric conditions (past and stable conditions will be allowed)
History of cardiac event or distress within the past 3 months
Currently pregnant (as indicated by urine pregnancy test at the start of each laboratory visit), planning to become pregnant, or breastfeeding (women only)
Use of other tobacco products (e.g., cigarette, cigar, etc.) > 5 days in the past month
Currently engaging in a tobacco product cessation attempt

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm I (pronated e-liquid, unprotonated e-liquid	Cigarette Smoking	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
Arm I (pronated e-liquid, unprotonated e-liquid	Computed Tomography	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
Arm I (pronated e-liquid, unprotonated e-liquid	Positron Emission Tomography	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
Arm I (pronated e-liquid, unprotonated e-liquid	Questionnaire Administration	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
Arm II (unprotonated e-liquid, protonated e-liquid	Cigarette Smoking	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.
Arm II (unprotonated e-liquid, protonated e-liquid	Computed Tomography	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.
Arm II (unprotonated e-liquid, protonated e-liquid	Positron Emission Tomography	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.
Arm II (unprotonated e-liquid, protonated e-liquid	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.

Primary Outcome Measures

Name	Time	Method
PET/CT Imaging of the Head	1.5 hours	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.
PET/CT Imaging of the Chest	1.5 hours	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.
Puff Volume (mL)	approx. 30 minutes	Puffing topography data was captured by the study e-cigarette to determine the puff volume.
Puff Duration (s)	approx. 30 minutes	Puffing topography data was captured by the study e-cigarette to determine the puff duration.
Age of First Tobacco Use	approx. 5 minutes	Age of first use will be assessed using the tobacco use history questionnaire.
Years of Tobacco Use	approx. 5 minutes	Years of tobacco use will be assessed using the tobacco use history questionnaire.
Years of Regular Use of Nicotine/Tobacco Products	approx. 5 minutes	Years of regular use of nicotine/tobacco products will be assessed using the tobacco history questionnaire
Past 30 Day Use of Nicotine/Tobacco Products	approx. 5 minutes	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.
Modified Cigarette Evaluation Questionnaire (mCEQ)	approx. 5 minutes	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.
Drug Effects Liking Questionnaire (DEQ)	approx. 5 minutes	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.
Modified Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form (QSU)	aprox. 5 minutes	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.
Minnesota Nicotine Withdrawal Scale	approx. 5 minutes	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.
Exhaled Breath Carbon Monoxide (CO)	approx. 5 minutes	Exhaled breath carbon monoxide was collected before each scan with a handheld electrochemical device.