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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cigarette Smoking-Related Carcinoma

Intervention / Treatment
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* Behavioral: Cigarette Smoking
* Behavioral: Cigarette Smoking
* Behavioral: Cigarette Smoking
* Behavioral: Cigarette Smoking
* Procedure: Computed Tomography
* Procedure: Positron Emission Tomography
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (pronated e-liquid, unprotonated e-liquid<br>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<br>* Receive 1 puff of tobacco flavored protonated e-liquid<br>Behavioral: Cigarette Smoking<br>* Receive 1 puff of unflavored protonated e-liquid<br>Behavioral: Cigarette Smoking<br>* Receive 1 puff of tobacco flavored unprotonated cigarette<br>Behavioral: Cigarette Smoking<br>* Receive 1 puff of unfavored unprotonated cigarette<br>Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Active Comparator: Arm II (unprotonated e-liquid, protonated e-liquid<br>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<br>* Receive 1 puff of tobacco flavored protonated e-liquid<br>Behavioral: Cigarette Smoking<br>* Receive 1 puff of unflavored protonated e-liquid<br>Behavioral: Cigarette Smoking<br>* Receive 1 puff of tobacco flavored unprotonated cigarette<br>Behavioral: Cigarette Smoking<br>* Receive 1 puff of unfavored unprotonated cigarette<br>Procedure: Computed Tomography<br>* Undergo PET/CT<br>* Other names: tomography;Procedure: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: proton magnetic resonance spectroscopic imaging;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PET/CT imaging of the head | Evaluate effect of nicotine form (free-base vs nicotine salt base) and concentration to determine nicotine absorption and distribution in the brain. | 1.5 hours | 
| PET/CT imaging of the chest | Evaluate effect of nicotine form (free-base vs nicotine salt base) and concentration to determine nicotine absorption and distribution in the raspatory tract. | 1.5 hours | 
| Puff volume | Puffing topography data will captured by the study E-Cig to determine the participant's typical puff volume. | approx. 30 minutes | 
| Puff duration | Puffing topography data will captured by the study E-Cig to determine the participant's typical puff volume. | approx. 30 minutes | 
| Tobacco use history questionnaire | Will assess years of tobacco use, age of first use, tobacco type, brand, frequency, quantity, and duration of use all of nicotine/tobacco products including cigars, cigarillos, little cigars, pipe tobacco, chewing tobacco, snuff, snus, EC/vape/mod/APV/e-hookah, and hookah tobacco. | approx. 5 minutes | 
| Modified Cigarette Evaluation Questionnaire (mCEQ) | Modified 12-item Cigarette Dependence Scale will measure nicotine dependence. | approx. 5 minutes | 
| Drug Effects Liking Questionnaire (DEQ) | Subjective effects and scaled questions. For scaled question the range is 1 to 5 with the lowest being the weekest and greatest being the strongest. | approx. 5 minutes | 
| Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form (modified) | Assess E-cig craving/suppression of craving and withdraw | aprox. 5 minutes | 
| Minnesota Nicotine Withdrawal Scale | Evaluate the effects of smoking cessation. Range 0-4, from none to severe. | approx. 5 minutes | 
| Exhaled breath carbon monoxide (CO) | Collect before each scan with a handheld electrochemical device. | approx. 5 minutes |