Comparative Evaluation of Nicotine Analogs

Conditions

• Addiction
• Tobacco-Related Carcinoma

Eligibility Criteria

Sex

ALL

Age

21 Years - N/A

Healthy Volunteers

Accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo urine and blood sample collection
• Nicotine — DRUG
  Use nicotine EC
• 6-Methyl Nicotine — DRUG
  Use 6-MN EC
• nicotinamide — DRUG
  Use nicotinamide EC
• Puffing Topography Research — BEHAVIORAL
  Ancillary studies
• Survey Administration — OTHER
  Ancillary studies
• Cardiovascular effects — PROCEDURE
  Cardiovascular effects will be measured using hemodynamic responses (i.e., blood pressure, pulse pressure, mean arterial pressure), arterial stiffness (i.e., central augmentation index), and endothelial function (i.e., plasma levels of endothelin-1, 6-keto-PGF1α, and nitric oxide metabolite).

Study Details

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.

Key Dates

Start date

Jun 1, 2026

Status verified

May 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

70 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

PREVENTION

Arms

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Primary Outcome Measure

Nicotine urges/craving (QSU) [ Time Frame: Before puffing (0 minutes), and at 5, 15, 65, 95, and 125 minutes after the start of the puffing session; at Visit 1 (baseline), Visit 2 (≥ 48 hours after the previous visit), and Visit 3 (end-of-study visit; ≥ 48 hours after the previous visit) ]

Central Contacts

• The Ohio State University Comprehensive Cancer Center
  800-293-5066
  [email protected]

Locations (1)

Find similar trials in Columbus, OH

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