Manipulating E-Cigarette Nicotine to Promote Public Health

Tobacco-Related Carcinoma Clinical Trial

Official title:

Manipulating E-Cigarette Nicotine to Promote Public Health

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06448351
• Other study ID #: OSU-23143
• Secondary ID: NCI-2023-05712
• Status: Recruiting
• Phase: N/A
• Start date: May 20, 2024
• Est. completion date: May 20, 2027

Study information

• Verified date: June 2024
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial explores the manipulation of e-cigarette (EC) nicotine to promote public health. Researchers are trying to understand and gather information about how the strength, form, and structure of nicotine in products play a significant role in their potential for addiction and how they might affect health risks. The information gained from this study may allow researchers to understand how these aspects of nicotine influence the potential for addiction, how people puff on ECs, how the body processes nicotine, and any potential harmful effects it might have on health. Exploring these specific characteristics of nicotine may also determine if an EC product standard could help identify optimal nicotine levels for users.

Description:

PRIMARY OBJECTIVES:

I. Assess the pharmacological, metabolic, and behavioral impact of nicotine dimensions. (Study 1) II. Assess the toxicity resulting from different nicotine dimension combinations. (Study 1) III. Across ecologically valid nicotine concentrations and isomer ratios, determine free-base (FB) nicotine fractions with minimal appeal to young adult EC users but sufficient appeal to smokers. (Study 2)

OUTLINE:

Phase 1 (STUDY 1): Participants are randomized to the order of 8 e-liquid combinations varying in nicotine concentration, form, and isomer.

Participants participate in a 10-puff vaping session over 5 minutes with a study e-liquid using the study EC device followed by a 60 minute washout period and then an ad libitum puffing session over 60 minutes at each lab visit. Patients are also given a new pre-filled study device corresponding to the study e-liquid they will use for the subsequent visit to practice at home. Puffing sessions continue with a new study e-liquid at each of the 8 lab visits lasting up to 4 hours each. Participants also undergo carbon monoxide (CO) testing and blood and urine sample collection on study.

Phase 2 (STUDY 2): Participants are randomized to the order of 20 e-liquid combinations varying in concentration, FB fractions, and isomer.

Participants will take part in a 2-puff vaping session with each of the 20 study e-liquids using the study EC device with a 10-minute washout period between each vaping session. Vaping sessions are grouped into two blocks of 10 separated by a 30 minute resting session over one lab visit lasting up to 6 hours. Participants also undergo CO testing and blood and urine sample collection on study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: May 20, 2027
• Est. primary completion date: May 20, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

• Current exclusive young adult EC user for at least the past 3 months (confirmed by cotinine testing strip) between 21-24 years old with no/minimal history of smoking cigarettes (< 10 cigarettes in entire life)

• Current older adult smoker (daily use, = 100 cigarettes in entire life) aged 25-65 with interest in trying an EC

• Willing to abstain from all nicotine, tobacco products, and marijuana for at least 12 hours before study visits

• Read and speak English

Exclusion Criteria:

• Currently attempting to quit nicotine or tobacco products

• Currently pregnant (will be verified with urine pregnancy test), planning to become pregnant, or breastfeeding

• Current daily use of other tobacco products other than ECs or cigarettes (use of > 10 traditional cigars, cigarillos, or filtered cigars in entire life; use of smokeless tobacco products > 10 times in entire life; or hookah in the last 30 days)

• Self-reported diagnosis of lung disease including asthma, cystic fibrosis, or chronic obstructive pulmonary disease

• New or unstable cardiovascular disease diagnosed within the past 3 months

• Use of medications that are inducers of CYP2A6 enzyme such as rifampicin, dexamethasone, phenobarbital, and other anti-convulsion drugs

Related Conditions & MeSH terms

• Tobacco-Related Carcinoma

Intervention

Procedure:
• Biospecimen Collection
Undergo blood and urine sample collection
• Carbon Monoxide Measurement
Undergo CO test

Other:
• Vaping session
Sample study e-liquids in vaping sessions at research lab with e-cig study device
• Survey Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nicotine pharmacokinetics: Maximum nicotine blood level (Cmax) (Study 1)	Blood nicotine samples will be assayed using liquid chromatography tandem mass spectrometry (LC-MS/MS) with deuterated internal standards.	Immediately before puffing (-5 minutes), and at 5, 15, 60, and 120 minutes after the start of the puffing session
Primary	Nicotine pharmacokinetics: Time to maximum blood level (Tmax) (Study 1)	Blood nicotine samples will be assayed using LC-MS/MS with deuterated internal standards.	Immediately before puffing (-5 minutes), and at 5, 15, 60, and 120 minutes after the start of the puffing session
Primary	Nicotine pharmacokinetics: Area under the curve (AUC) (Study 1)	Blood nicotine samples will be assayed using LC-MS/MS with deuterated internal standards.	Immediately before puffing (-5 minutes), and at 5, 15, 60, and 120 minutes after the start of the puffing session
Primary	Nicotine metabolism (Study 1)	The rate of nicotine metabolism will be assessed using the standard method of nicotine metabolite ration (NMR) = hydroxycotinine/cotinine, modified to reflect stereoselective metabolism. Plasma concentration of cotinine, and hydroxycotinine will be measured by chiral LC-MS/MS based on previous methods and quantified using the ratio of metabolites to internal standards.	At 60 minutes after the start of each puffing session
Primary	Reactive oxygen species (ROS) (Study 1)	The recorded puffing topographies will be sent to the analytical lab for "puff playback" generation of EC aerosols and quantification of ROS. We will use an acellular ROS assay previously developed by our team as a generic toxicity assessment method.	Up to 2 years
Primary	Nicotine toxicity measures (Study 1)	Will be assessed by carbonyl yields reported as ug/session or ug/puff or normalized per nicotine yield for a head-to-head comparison between different nicotine conditions.	Up to 2 years
Primary	In vitro nicotine toxicity measures: Cell cycle and proliferation (Study 1)	Will be assessed by cell cycle and proliferationg.	Up to 2 years
Primary	In vitro nicotine toxicity measures: Cytotoxicity (Study 1)	Will be assessed by cytotoxicity, senescence.	Up to 2 years
Primary	In vitro nicotine toxicity measures: Senescence (Study 1)	Will be assessed by senescence.	Up to 2 years
Primary	In vitro nicotine toxicity measures: RNA sequencing (Study 1)	Will be assessed by RNA sequencing.	Up to 2 years
Primary	Nicotine yield (Study 1)	Using a dilute-and-shoot method developed by our team, nicotine yield in EC aerosol will be quantified using the "playback" technique (i.e., use topography collected from participants to machine-generate EC aerosols) and GC-MS method, developed by our group to minimize the PG/VG interference not addressed by other methods.	Up to 2 years
Primary	Modified Cigarette Evaluation Questionnaire (mCEQ)(Study 1)	The modified Cigarette Evaluation Questionnaire (mCEQ) will assess subjective responses. The 11-item mCEQ includes five subscales: Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations, and Craving Reduction, with items rated from 1 (not at all) to 7 (extremely likely). Items are averaged to create each of the subscales also ranging from 1 to 7 with higher values indicating greater levels of smoking satisfaction, psychological reward, aversion, enjoyment of respiratory tract sensations, and craving reduction.	Study visits 2 through 9
Primary	Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form (QSU)	Smoking and vaping urges/craving will be measured using the Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form with a modified version (replacing the word "cigarette" with "e-cigarette") for EC users. This is a 10-item measure where participants rate smoking/vaping-related items 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/vape; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 35 for each of the factors with higher scores indicating greater craving to smoke/vape.	Study visits 2 through 9
Primary	Drug Effects/Liking Questionnaire (DEQ)(Study 1)	Assess the desire and liking of products, positive and negative effects (i.e., side effects), and perceived strength and effectiveness. Scores range from 1 to 5 with higher scores indicating greater strength (effect from smoking cigarettes/vaping e-cigarettes) or liking (liking of effect from smoking cigarettes/vaping e-cigarettes)	Study visits 2 through 9
Primary	Minnesota Nicotine Withdrawal Scale (MNWS)(Study 1)	Asses Nicotine withdrawal and smoking craving, anger/irritability, anxiety, depressed mood, restlessness/difficulty concentrating, increased appetite, sleep problems, and somatic symptoms (nausea, constipation, sore throat, dizziness, coughing). Scores range from 0 to 4 with higher scores indicating greater levels of withdrawal (MNWS) or more craving to smoke (MNWS Craving).	Study visits 2 through 9
Primary	Puffing topography: Puff count (Study1)	Puff count will be measured.	60 minute puffing session at each of the 8 study lab visits
Primary	Puffing topography: Average puff duration (Study1)	Average puff duration will be measured.	60 minute puffing session at each of the 8 study lab visits
Primary	Puffing topography: inter-puff interval (Study1)	Inter-puff interval will be measured.	60 minute puffing session at each of the 8 study lab visits
Primary	Puffing topography: Flow rate (Study1)	Flow rate will be measured.	60 minute puffing session at each of the 8 study lab visits
Primary	Puffing topography: Volume (Study1)	Puff volume will be measured.	60 minute puffing session at each of the 8 study lab visits
Primary	General Labeled Magnitude Scale (gLMS) (Study 2)	Complete the General Labeled Magnitude Scale (gLMS) after each condition. Scores range from 0 "No Sensation" to 100 "Strongest Imaginable".	1 six hour lab visit
Primary	Labeled Hedonic Scale (LHS) (Study 2)	Complete the Labeled Hedonic Scale (LHS) after each condition. Scores range from -100 "Most Disliked Imaginable" to 100 "Most Liked Imaginable".	1 six hour lab visit
Primary	Sensory Attributes (Study 2)	Rate sensory attributes (smoothness, harshness, sweetness, bitterness) on a 100-unit visual analog scale after each condition.	1 six hour lab visit
Primary	Overall acceptance: Industry-designed Thermometer Rating Scale (Study 2)	Complete a tobacco industry-designed thermometer rating scale of overall acceptance after each condition. Ratings range from 0 "the very worst" to 100 "the very best", with 50 indicating "indifferent".	1 six hour lab visit