Nicotine Flux, a Potentially Powerful Tool for Regulating Nicotine Delivery From Electronic Cigarettes

NCT05706701 | Completed Results

• 2 other identifiers: 20000319731R01DA052565-01A1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will examine the relationship between nicotine flux, nicotine form, and the rate and dose of nicotine delivery. Participants will puff on electronic nicotine delivery system (ENDS) devices under conditions that differ by flux and form, while arterial blood is sampled in high time resolution. The outcome will indicate the degree to which nicotine flux and form determine the speed and dose of ENDS nicotine delivery, and thus, abuse liability.

Conditions

Nicotine Vaping

Keywords

Nicotine; Nicotine Flux; ENDS

Outcome Measures

Primary Outcomes (1)

• Change in Maximum Arterial Blood Nicotine Delivery (Cmax)

  For arterial blood sampling, a radial arterial line will be placed on the non-dominant side to provide access to blood samples during vaping sessions. Blood will be sampled 30sec prior to the initial puff, 5, 15, and 25sec after each puff, and 60sec after the last puff of a bout (3 puffs per bout; 4 bouts per visit day; two visit days, separated by three weeks). The obtained data will be used to calculate pharmacokinetic parameters of nicotine delivery under each condition.

  Day 1 and Week 3

Secondary Outcomes (5)

• Change in Area Under the Curve for Nicotine (AUC)

  Day 1 and Week 3

• Change in Liquid Consumed

  Day 1 and Week 3

• Mean Change in Puff Topography

  Day 1 and Week 3

• Change in Rate of Nicotine Rise After the Initial Puff (dCi/dt)

  Day 1 and Week 3

• Change in Time to Maximum Arterial Blood Level Nicotine Concentration (Tmax)

  Day 1 and Week 3

Study Arms (2)

Nicotine vaping group visit 1

EXPERIMENTAL

Subjects will receive the either free-base or protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their first of two visits. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.

Other: Nicotine vaping visit 1 (free-base nicotine); Other: Nicotine vaping visit 2 (protonated nicotine)

Nicotine vaping group visit 2

EXPERIMENTAL

The same subjects from visit 1 will receive the either free-base or protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their second study visit, using the opposite nicotine form that was used during the first visit.

Other: Nicotine vaping visit 1 (protonated nicotine); Other: Nicotine vaping visit 2 (free-base nicotine)

Interventions

Nicotine vaping visit 1 (free-base nicotine) OTHER

Participants will receive the free-base form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at one of their two visits. Participants will use the ENDS device with free-base nicotine and four fluxes in random order.

Nicotine vaping group visit 1

Nicotine vaping visit 1 (protonated nicotine) OTHER

Participants will receive the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at the other study visit. Participants will use the ENDS device with protonated nicotine and four fluxes in random order.

Nicotine vaping group visit 2

Nicotine vaping visit 2 (free-base nicotine) OTHER

Participants who received protonated nicotine during visit 1 will now receive free-base nicotine fluxes for visit 2: 9, 18, 27, 35 μg/sec.

Nicotine vaping group visit 2

Nicotine vaping visit 2 (protonated nicotine) OTHER

Participants who received free-base nicotine during visit 1 will now receive protonated nicotine fluxes for visit 2: 9, 18, 27, 35 μg/sec.

Nicotine vaping group visit 1

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Above 21 years of age
• Use ENDS at least 3 months and at least 3 times a week.
• Be willing to provide informed consent, attend the lab, and abstain from tobacco/nicotine as required.
• Have a normal Allen test

You may not qualify if:

• Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, or hepatic pathology that would increase risk or would interfere with/mimic tobacco abstinence
• Untreated, unresolved active pulmonary or cardiovascular conditions (i.e. chest pain, dyspnea, acute infection, recurring bronchitis, and reactive airway disorder)
• Breast-feeding or Pregnant (by urinalysis at screening).
• Vaping less than 3 months and less than 3 times per week
• Taking anticoagulants and blood thinners
• Known hypersensitivity to propylene glycol
• History of environmental - bronchospastic allergies, multiple chemical sensitivities, or other airway sensitivities that require the use of an epi pen or that in the investigator's view would make it risky for participation.
• Has current symptoms as identified by the Health Assessment Checklist including cough, shortness of breath, chest pain, nausea, vomiting, stomach pain, diarrhea, fever, chills, or weight loss
• Participants intending to quit tobacco/nicotine use in the next 30 days will be excluded and referred to cessation treatment.
• Abnormal Allen Test (impaired collateral circulation)
• Positive pregnancy test at any study visit
• Infection of skin or soft tissue at insertion site (erythema, swelling, ulceration)
• Peripheral vascular disease
• Coronary artery disease/advance atherosclerosis
• Raynaud's phenomenon

Sponsors & Collaborators

• Yale University: lead
• American University of Beirut Medical Center: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Human Research Unit (HRU)

New Haven, Connecticut, 06510, United States

Location

Related Publications (1)

• El-Hellani A, Hanna E, Sharma M, Blohowiak R, Joseph P, Eid T, Nadim H, El-Hage R, Salman R, Karaoghlanian N, Adeniji A, Salam S, Talih F, Elbejjani M, Breland A, Eissenberg T, Shihadeh A, Baldassarri SR, Talih S. Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials. PLoS One. 2023 Sep 21;18(9):e0291786. doi: 10.1371/journal.pone.0291786. eCollection 2023.

  PMID: 37733666 DERIVED

MeSH Terms

Conditions

Vaping

Condition Hierarchy (Ancestors)

Smoking; Behavior

Results Point of Contact

• Title: Stephen R Baldassarri, M.D.
• Organization: Yale University

stephen.baldassarri@yale.edu

203-785-3627

Study Officials

• Stephen R Baldassarri, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The flux/form conditions will be tested by participants in two lab visits separated by three weeks to minimize carryover effects. All sessions will be double-blinded. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The investigators will measure arterial nicotine concentrations over discrete time-periods in a within-subject study with 15 anticipated participants who will undergo 2 ENDS use sessions that differ by nicotine form (protonated, freebase). In each session, participants will draw three 3-sec puffs with four randomly ordered nicotine fluxes (9, 18, 27, 35 μg/sec).

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 31, 2023
• Study Start: February 1, 2023
• Primary Completion: May 17, 2024
• Study Completion: May 17, 2024
• Last Updated: November 18, 2025
• Results First Posted: November 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)