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.
Interventions
Biospecimen Collection
Undergo urine and blood sample collection
6-Methyl Nicotine
Use 6-MN EC
nicotinamide
Use nicotinamide EC
Puffing Topography Research
Ancillary studies
Survey Administration
Ancillary studies
Cardiovascular effects
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).