Comparative Evaluation of Nicotine Analogs
Purpose
This phase I trial compares electronic cigarette (EC) user preferences and smoking behaviors of nicotine analogs to nicotine to improve the understanding of nicotine analog addictiveness. Over the last ten years, EC use has become a major concern due to its increased use among adolescents and young adults. Though progress has been made in regulating nicotine containing products, some companies have shifted toward producing products containing nicotine analogs. ECs are battery-powered electronic devices designed to atomize a nicotine (the poisonous chemical found in tobacco)-containing liquid solution for inhalation in a manner that simulates smoking a tobacco cigarette. When nicotine enters the body, it causes an increased heart rate and use of oxygen by the heart, and a sense of well-being and relaxation. Nicotine analogs are compounds that are similar to nicotine in their chemical structure. Some nicotine analogs have been shown to have nicotine-like effects; however, more research is needed to prove they function similarly to nicotine and/or have similar effects. Comparing EC user preferences and smoking behaviors of nicotine analogs to nicotine may help improve the understanding of nicotine analog addictiveness. Additionally, combustible cigarette smoking is well-known to have deleterious effects on cardiovascular health. High blood pressure is one of the major health consequences of cigarette smoking and can increase the risk of hypertension, heart attack, and stroke. Although ECs have been marketed as a less harmful alternative to cigarette smoking, clinical trials have shown that vaping ECs can also lead to acute increases in blood pressure and heart rate. Nicotine can alter vascular reactivity by promoting the release of vasoconstrictors and suppressing the production of vasodilators. No research has examined how the synthetic nicotine in ECs affects hemodynamics, vascular health, and endothelial function. Assessing acute cardiovascular responses to nicotine analogs is therefore critical to enhancing our understanding of the potential cardiovascular risks associated with vaping ECs containing synthetic nicotine.
Conditions
- Tobacco-Related Carcinoma
- Addiction
Eligibility
- Eligible Ages
- Over 21 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Aged 21 years or older - Current adult EC user for at least the past 3 months (confirmed by cotinine testing strip) - Willing and able to provide informed consent - Willing to abstain from using any nicotine, tobacco, or marijuana products for 12 or more hours prior to the three lab visits - Able to read, write, and speak English
Exclusion Criteria
- Currently attempting to quit nicotine or tobacco products - Use of other tobacco or nicotine products > 10 days in the past month - Have had a recent cardiac event or distress (defined as occurring within the previous 3 months) - Have had a recent serious lung disease or infection (e.g., tuberculosis, cystic fibrosis, asthma, or lung cancer) (defined as occurring in the previous 30 days) - Currently pregnant, planning to become pregnant, or breastfeeding (verified with urine pregnancy test)
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover Assignment
- Primary Purpose
- Prevention
- Masking
- Single (Participant)
- Masking Description
- Data collectors, analysts, and participants will be blinded to the intervention sequence.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Sequence 1 (nicotine, 6-MN, nicotinamide) |
VISIT 1: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. Patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. |
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Experimental Sequence 2 (nicotine, nicotinamide, 6-MN) |
VISIT 1: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. Patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. |
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|
Experimental Sequence 3 (nicotinamide, 6-MN, nicotine) |
VISIT 1: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. Patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. |
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|
Experimental Sequence 4 (nicotinamide, nicotine, 6-MN) |
VISIT 1: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. Patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. |
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|
Experimental Sequence 5 (6-MN, nicotine, nicotinamide) |
VISIT 1: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. Patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. |
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Experimental Sequence 6 (6-MN, nicotinamide, nicotine) |
VISIT 1: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. Patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. |
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Recruiting Locations
Columbus, Ohio 43210
More Details
- Status
- Recruiting
- Sponsor
- Ohio State University Comprehensive Cancer Center
Study Contact
The Ohio State University Comprehensive Cancer Center800-293-5066
OSUCCCClinicaltrials@osumc.edu
Detailed Description
PRIMARY OBJECTIVES: I. To assess the subjective effects and behavioral economic demand of 6-methyl nicotine (6-MN) and nicotinamide. II. To assess the use topography of 6-MN and nicotinamide. III. To conduct exploratory pharmacokinetics of 6-MN and nicotinamide. IV. To assess the acute effects of 6-MN and nicotinamide on cardiovascular health. OUTLINE: Participants are randomized to 1 of 6 intervention sequences. SEQUENCE 1: VISIT 1: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. SEQUENCE 2: VISIT 1: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. SEQUENCE 3: VISIT 1: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. SEQUENCE 4: VISIT 1: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. SEQUENCE 5: VISIT 1: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. SEQUENCE 6: VISIT 1: Participants take 1 puff of 6-MN EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use 6-MN EC as much or as little as they like over 1 hour. VISIT 2: Participants take 1 puff of nicotinamide EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotinamide EC as much or as little as they like over 1 hour. VISIT 3: Participants take 1 puff of nicotine EC every 30 seconds over 5 minutes for a total of 10 puffs in the absence of unacceptable toxicity. Sixty minutes later, participants use nicotine EC as much or as little as they like over 1 hour. Additionally, all patients undergo urine sample collection during screening and blood sample collection on study. Among enrolled current EC users, cardiovascular measurements and biochemical analyses of endothelial function will be conducted in a subset of the participants. After completion of study intervention, participants are followed up at 4 and 12 weeks.