Clinical trial NCT02470754: Clinical Pharmacology of Electronic Cigarettes
Official title: Clinical Pharmacology of Electronic Cigarettes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Dependence
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Roswell Park Cancer Institute
name: National Institute on Drug Abuse (NIDA)
First posted: 2015-06-12
Enrollment: 38
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to learn more about nicotine exposure and the safety of electronic cigarettes (EC). It will focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving.

Detailed description: Electronic cigarettes (EC) are nicotine delivery devices that generate a nicotine-containing aerosol which is inhaled by the user. EC are perceived by users to be useful in helping quitting smoking of conventional tobacco cigarettes (TC) as well as having a presumed lower risk of adverse health effects compared to TC, the potential for use in public places, reduced cost, and lack of the noxious clinging odors associated with TC use. Many believe that electronic cigarette (EC) function as nicotine delivery devices in the same way as tobacco cigarettes (TC), and that EC will prove to be just as addictive as TC, but this may not be the case because of fundamental differences in the design and method of use of these products. Investigators hypothesize that systemic nicotine exposure will be lower with EC compared to TC; that despite lower nicotine intake EC users will experience similar reward and no greater withdrawal symptoms or craving compared to TC; and that dual EC/ TC users will not titrate their daily intake of nicotine in the same way that TC smokers of high- vs low-yield nicotine TC do.

Investigators specifically focus on the areas that are thought to most closely relate to the addictive potential of EC, namely: (1) EC as nicotine delivery devices, covering issues of nicotine intake and pharmacokinetics, temporal patterns of use and titration of nicotine; and (2) subjective effects of EC use, including relationship of use to reward, withdrawal and craving. The investigators will also examine aspects of safety of EC use (by assessment of cardiovascular and hormonal effects of use and of biomarkers of exposure to potentially toxic constituents) and explore the identification and validation of biomarkers that may be useful in distinguishing EC from TC use. Study subjects will be dual users of TC and EC so that the investigators may compare both modalities of use in experienced users in a within-subject design.

The study will consist of two 1-week blocks (EC-only or TC-only conditions) with 4 days of outpatient ad libitum product use followed by 3 days in a clinical research ward to include a single-use pharmacokinetic study, monitoring of product use, subjective assessments, blood and urine collections to assess biomarkers, and a 24-hour period of cardiovascular monitoring. Two additional days at the end of the 2nd block will assess similar measurements during a period of nicotine-product abstention.

Eligibility criteria: Inclusion Criteria:

* Healthy on the basis of medical history and limited physical examination as described below:

  * Heart rate \< 105 BPM\*
  * Systolic Blood Pressure \< 160 and \> 90\*
  * Diastolic Blood Pressure \< 100 and \> 50\*
  * Body Mass Index ≤ 38.0 \*Considered out of range if both machine and manual readings are above/below these thresholds.
* Current regular "dual" user of both EC and conventional TC
* EC device is one of the most popular 1st, 2nd or 3rd generation brands (with the exception of rebuildable atomizers) as determined at time of study commencement
* Carbon monoxide ≥ 5 ppm or per discretion of Principal Investigator
* Saliva cotinine ≥50 ng/ml or urine cotinine
* Age: ≥ 21 years

Exclusion Criteria:

* Current regular use of selected psychiatric medications
* Current regular use of cardiovascular medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers)
* Current regular use of medications inducers of nicotine metabolizing enzymes CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).
* Use of other tobacco products
* Pregnancy or breastfeeding (by history and pregnancy test)
* Concurrent use of nicotine-containing medications
* Drug/Alcohol Dependence
* Positive toxicology test at the screening visit (THC okay)
* Concurrent participation in another clinical trial
* Inability to communicate in English
* Planning to quit smoking within the next 60 days

Primary outcomes:
measure: Standardized Session: Mean CMax
timeFrame: Inpatient Day 1, Up to 4 Hours post Nicotine Administration
measure: Standardized Session: Mean TMax
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: Standardized Session: AUC 0-240
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: PK-estimated Nicotine Dose
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
Secondary outcomes:
measure: Standardized Session: QSU Factor 1 (Vaping)
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: Standardized Session: Positive and Negative Affect Score (Negative Affect)
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: Standardized Session: Minnesota Nicotine Withdrawal Scale
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: Standardized Session: QSU Factor 2 (Vaping)
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: Standardized Session: QSU Factor 1 (Smoking)
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
measure: Standardized Session: QSU Factor 2 (Smoking)
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
Other outcomes:
measure: Standardized Session: Half-life
timeFrame: Inpatient Day 1, Up to 4 Hours post Session
Locations:
city: San Francisco
country: United States
facility: San Francisco General Hospital (SFGH)
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF)
state: California
Study officials:
affiliation: University of California, San Francisco
name: Neal L Benowitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benowitz NL, St Helen G, Nardone N, Addo N, Zhang JJ, Harvanko AM, Calfee CS, Jacob P 3rd. Twenty-Four-Hour Cardiovascular Effects of Electronic Cigarettes Compared With Cigarette Smoking in Dual Users. J Am Heart Assoc. 2020 Dec;9(23):e017317. doi: 10.1161/JAHA.120.017317. Epub 2020 Nov 19.