A Phase 1 interventional study of Biospecimen Collection and Nicotine in Tobacco-Related Carcinoma and Addiction, sponsored by Ohio State University Comprehensive Cancer Center. Recruiting at 1 site in United States. Open to participants aged 21 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-26.
Sponsored by Ohio State University Comprehensive Cancer Center · Phase 1, Interventional, and Prevention
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.
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.
521 studies on the registry are indexed under Behavior, Addictive; 124 are open to participants now.
This study's planned enrollment of 70 is above the median of 62 across 399 interventional studies indexed under Behavior, Addictive.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Procedure: Biospecimen Collection · Drug: Nicotine · Drug: 6-Methyl Nicotine · Drug: nicotinamide · Behavioral: Puffing Topography Research · Other: Survey Administration · Procedure: Cardiovascular effects
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.
Procedure: Biospecimen Collection · Drug: Nicotine · Drug: 6-Methyl Nicotine · Drug: nicotinamide · Behavioral: Puffing Topography Research · Other: Survey Administration · Procedure: Cardiovascular effects
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.
Procedure: Biospecimen Collection · Drug: Nicotine · Drug: 6-Methyl Nicotine · Drug: nicotinamide · Behavioral: Puffing Topography Research · Other: Survey Administration · Procedure: Cardiovascular effects
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.
Procedure: Biospecimen Collection · Drug: Nicotine · Drug: 6-Methyl Nicotine · Drug: nicotinamide · Behavioral: Puffing Topography Research · Other: Survey Administration · Procedure: Cardiovascular effects
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.
Procedure: Biospecimen Collection · Drug: Nicotine · Drug: 6-Methyl Nicotine · Drug: nicotinamide · Behavioral: Puffing Topography Research · Other: Survey Administration · Procedure: Cardiovascular effects
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.
Procedure: Biospecimen Collection · Drug: Nicotine · Drug: 6-Methyl Nicotine · Drug: nicotinamide · Behavioral: Puffing Topography Research · Other: Survey Administration · Procedure: Cardiovascular effects
Undergo urine and blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Use nicotine EC
Also known as: (-)-Nicotine, NIC
Use 6-MN EC
Also known as: 6-MN, Nixodine, Nixotine
Use nicotinamide EC
Also known as: NAM, Nixamide, Nixodine
Ancillary studies
Ancillary studies
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).
Nicotine urges/craving (QSU)
E-cigarette (EC) urges/craving will be measured with a modified version of the 10-item Tiffany-Drobes Questionnaire of Smoking Urges: Brief Form (QSU). Words such as "cigarette" and "smoke" are replaced with words such as "e-cigarette" and "vape." Each of the 10 items is scored on a 7 point Likert scale. Similar to previous studies, we will collapse the items into two previously identified factors (Factor 1: strong desire and intention to smoke; Factor 2: anticipation of relief from withdrawal symptoms). Scores are calculated by summing the items and range from 5 to 35 with higher scores indicating greater craving to smoke.
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)
Nicotine withdrawal symptoms (MNWS)
The 15-item version of the Minnesota Nicotine Withdrawal Scale (MNWS) will be used to measure nicotine withdrawal symptoms. Items are rated on a 5-point scale from 0 (none) to 4 (severe) where higher scores indicate a greater experience of withdrawal symptoms.
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)
Economic demand indices (E-CPT)
Consumer demand as measured by the E-Cigarette Purchase Task (E-CPT) will be used to measure economic demand. Participants will report the volume (mLs) or puffs of e-liquid they would be willing to purchase and use within 24 hours at a given price, which will incrementally increase from $0 to $1,120.
Time frame: After completion of the 60 minute ad lib 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)
Modified EC evaluation questionnaire (mCEQ)
The modified EC Evaluation Questionnaire (mCEQ) will be used to measure sensory effects, affective responses, and other subjective responses (e.g., reward, satisfaction). The 12-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). 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, an craving reduction.
Time frame: After completion of the 60 minute ad lib 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)
Use topography: Inter-puff-interval
The average time between each puff for each participant, in seconds.
Time frame: 60 minute 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)
Use topography: Puffing duration
Average puff duration for each participant, in seconds.
Time frame: 60 minute 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)
Use topography: Total puff volume
The total volume of all puffs taken for each participant, in mL.
Time frame: 60 minute 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)
Nicotine/Nicotine analog pharmacokinetics: Cmax
Maximum blood concentration of nicotine/nicotine analog.
Time frame: Immediately before puffing (0 minutes), and at 5, 15, 65, 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)
Nicotine/Nicotine analog pharmacokinetics: Tmax
Time to maximum blood concentration of nicotine/nicotine analog.
Time frame: Immediately before puffing (0 minutes), and at 5, 15, 65, 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)
Heart rate
Heart rate
Time frame: Immediately before puffing (0 minutes), and at 5, 15, 65, 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)
Cardiovascular responses
Hemodynamics and arterial stiffness
Time frame: Immediately before puffing (0 minutes), and at 5 minutes after the end of standardized vaping 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)
Endothelial function
Endothelial biomarker levels will be quantified from blood samples collected immediately before puffing.
Time frame: Immediately before puffing (0 minutes) and 15 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)
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Studies of the drug tested here: Nicotine
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