Manipulating E-Cigarette Nicotine to Promote Public Health

Overview

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.

Detailed 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 20-minute washout period between each vaping session. Vaping sessions are grouped into two visits, each lasting up to 5 hours and consisting of 10 e-liquids. Participants also undergo CO testing and blood and urine sample collection on study.

Interventions

• Procedure Biospecimen Collection
  Undergo blood and urine sample collection
• Procedure Carbon Monoxide Measurement
  Undergo CO test
• Other Vaping session
  Sample study e-liquids in vaping sessions at research lab with e-cig study device
• Other Survey Administration
  Ancillary studies

Primary outcome measures

• Nicotine pharmacokinetics: Maximum nicotine blood level (Cmax) (Study 1) [Time frame: Immediately before puffing (-5 minutes), and at 5, 15, 60, and 120 minutes after the start of the puffing session]
• Nicotine pharmacokinetics: Time to maximum blood level (Tmax) (Study 1) [Time frame: Immediately before puffing (-5 minutes), and at 5, 15, 60, and 120 minutes after the start of the puffing session]
• Nicotine pharmacokinetics: Area under the curve (AUC) (Study 1) [Time frame: Immediately before puffing (-5 minutes), and at 5, 15, 60, and 120 minutes after the start of the puffing session]
• Nicotine metabolism (Study 1) [Time frame: At 60 minutes after the start of each puffing session]
• Reactive oxygen species (ROS) (Study 1) [Time frame: Up to 2 years]
• Nicotine toxicity measures (Study 1) [Time frame: Up to 2 years]
• In vitro nicotine toxicity measures: Cell cycle and proliferation (Study 1) [Time frame: Up to 2 years]
• In vitro nicotine toxicity measures: Cytotoxicity (Study 1) [Time frame: Up to 2 years]
• In vitro nicotine toxicity measures: Senescence (Study 1) [Time frame: Up to 2 years]
• In vitro nicotine toxicity measures: RNA sequencing (Study 1) [Time frame: Up to 2 years]

Eligibility criteria

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 for Study 1 and 2 hours for Study 2 before study visits
• Read, write, 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
• If age 21-24 years old AND use of any tobacco products other than ECs (use of >10 cigarettes in entire life; 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Factorial

Masking

Double blind

Primary purpose

Prevention

Study locations

United States · 1 center

• Ohio State University Comprehensive Cancer Center — Columbus

Identifiers

NCT: NCT06448351 · OSU-23143 · NCI-2023-05712

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗