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N/A N=26 Randomized Double-blind Other

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

Nicotine Vaping

Enrolled (actual)
26
Serious AEs
1.0%
Results posted
Nov 2025
Primary outcome: Primary: Change in Maximum Arterial Blood Nicotine Delivery (Cmax) — 3.75; 2.48; 8.12; 2.96 ng/ml

Study Design & Population

Study type
Interventional
Phase
N/A
Interventions
Nicotine vaping visit 1 (free-base nicotine) (Other); Nicotine vaping visit 1 (protonated nicotine) (Other); Nicotine vaping visit 2 (free-base nicotine) (Other); Nicotine vaping visit 2 (protonated nicotine) (Other)
Age
Adult, Older Adult · 21+ yrs
Sex
All
Sponsor
Yale University
Primary completion
May 2024

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Maximum Arterial Blood Nicotine Delivery (Cmax)
3.75; 2.48; 8.12; 2.96; 13.23; 5.13
SECONDARY
Change in Area Under the Curve for Nicotine (AUC)
316.06; 225.68; 643.48; 255.38; 1022.42; 443.79
SECONDARY
Change in Liquid Consumed
0.08; 0.08; 0.02; 0.09; 0.03; 0.09
SECONDARY
Mean Change in Puff Topography
2.81; 2.78; 2.81; 2.66; 2.83; 2.3
SECONDARY
Change in Rate of Nicotine Rise After the Initial Puff (dCi/dt)
0.12; 0.09; 0.28; 0.08; 0.44; 0.13
SECONDARY
Change in Time to Maximum Arterial Blood Level Nicotine Concentration (Tmax)
93.83; 102.88; 100.32; 99.81; 99; 106.31

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.

Eligibility Criteria

Inclusion Criteria

  • 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

Exclusion Criteria

  • 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
  • Coagulopathy (hereditary bleeding disorders, advanced liver disease)
  • Thromboangiitis obliterans
  • COPD/emphysema/chronic bronchitis
  • Allergy to lidocaine or anesthetics
  • Inability to tolerate blood draws for any reason
  • Additional Screening Procedures: Significant changes and/or abnormalities in these assessments during the study period may warrant exclusion at the discretion of the PI.
  • Participants will be asked to answer the 4-item Patient-Reported Outcomes Measurement Information System (PROMIS) physical function scale and will be excluded if they report greater than "without any difficulty" on any single item as a screening tool
  • Spirometry (baseline and before each visit)
  • Physical Exam
  • Application of the self-reported signs and symptoms health questionnaire with exclusion of those with chronic symptoms that would interfere with monitoring of vaping complications (baseline and * before each visit). Participants will be excluded and referred for medical treatment if they indicate dyspnea or cough symptoms are "severe."
  • PROMIS Dyspnea Severity Item Pool
  • PROMIS Dyspnea Characteristics
  • PROMIS Fatigue Short Form
  • Functional Assessment of Chronic Illness Therapy (FACIT) Cough item
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT05706701). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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