Nicotine Delivery From Novel Non-Tobacco Electronic System in Smokers (ENDS)

Nicotine Delivery From Novel Non-tobacco Electronic Systems (ENDS)

This randomized pilot clinical trial studies nicotine delivery from novel non-tobacco electronic system (ENDS) in smokers. Studying the levels of nicotine delivered by various types and brands of ENDS to the bloodstream, and comparing this to the levels delivered from conventional cigarettes (the participant's own brand) may help provide information about the use of nicotine-containing products that may help inform/reform current tobacco policy, practice, and harm reduction approaches.

Study Overview

• Status: Completed
• Conditions: Current Smoker; Healthy Subject; Cigarette Smoker
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Questionnaire Administration; Other: Electronic Cigarette; Other: Electronic Cigarette

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes. (Study 1)

II. Explore the effect of flavorings added to nicotine solution on puffing topography and nicotine delivery and, assess and compare short-term "functional" nicotine effects of the different products by using subjective measures such as relief of craving and withdrawal symptoms. (Study 2)

SECONDARY OBJECTIVES:

I. Determine the amounts of nicotine present in various brands and types of ENDS. (Study 3)

II. Determine nicotine yields in vapors from various types of ENDS under laboratory conditions. (Study 4)

TERTIARY OBJECTIVES:

I. Develop a standardized testing protocol for ENDS that will reflect users' puffing behavior and product characteristics.

II. Develop and validate the analytical method for analysis of nicotine content in the vapor.

III. Propose a standardized puffing regimen for generating vapors for analytical purposes: Such a testing protocol will reflect the puffing behavior observed among ENDS users and should be specific to ENDS type.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I (Study 1): Participants are asked to smoke ad lib a single cigarette of their own brand and provided with a different type of ENDS product at each visit (e-cigarette, disposable e-cigarette, eGo, personal vaporizer, e-cigar, and e-pipe) over 3.5-4 hours at least 7 days apart for 7 weeks. Participants are provided with cartridges of the same amounts of nicotine with regular (tobacco) or menthol flavor according to smoker's preference, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit.

ARM II (Study 2): Participants are asked to smoke ad lib a single cigarette of their own brand and provided with the BLU e-cigarette ENDS product with nicotine solution of one of five flavors over 3.5-4 hours at least 7 days apart for 6 weeks. Participants are provided with cartridges of maximum available amounts of nicotine and different flavors at each visit, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy on the basis of medical history

• Current moderate-to-heavy smoker as determined by:

  • Has smoked >=10 cigarettes per day regularly for the past year (by history) and (>=5 cigarettes per day Study 2 ONLY)
  • Has an expired carbon monoxide (CO) at screening visit of 8 parts per million (ppm) or more (6 ppm or more Study 2 ONLY)
• Nicotine dependence assessed as > 4 with the Fagerstrom Test for Nicotine Dependence
• Willingness to abstain from smoking for 8 hours (overnight abstinence) prior to study visits
• Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

• Unstable medical conditions (such as unstable heart disease, uncontrolled hypertension, thyroid disease, diabetes, renal or liver impairment, glaucoma, or prostatic hypertrophy) or psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder, or current regular use of psychiatric medications such as major tranquilizers and antidepressants
• Pregnancy or lactation (by history) or positive pregnancy test at screening visit
• Positive urine drug test at screening visit
• History of serious side effects from nicotine or from any nicotine replacement therapies
• Alcohol or illicit drug dependence within the past 12 months (by history and urine tests)
• Concurrent participation in another clinical trial
• Unable to communicate in English
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (different type of ENDS product at each visit); Participants are asked to smoke ad lib a single cigarette of their own brand and provided with a different type of ENDS product at each visit (e-cigarette, disposable e-cigarette, eGo, personal vaporizer, e-cigar, and e-pipe) over 3.5-4 hours at least 7 days apart for 7 weeks. Participants are provided with cartridges of the same amounts of nicotine with regular (tobacco) or menthol flavor according to smoker's preference, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Electronic Cigarette; Receive different type of ENDS product at each visit; Other Names: e-Cigarette; Electronic Nicotine Delivery System; Other: Electronic Cigarette; Receive BLU e-cigarette ENDS product; Other Names: e-Cigarette; Electronic Nicotine Delivery System
Experimental: Arm II (BLU e-cigarette ENDS product with different flavors); Participants are asked to smoke ad lib a single cigarette of their own brand and provided with the BLU e-cigarette ENDS product with nicotine solution of one of five flavors over 3.5-4 hours at least 7 days apart for 6 weeks. Participants are provided with cartridges of maximum available amounts of nicotine and different flavors at each visit, instructed on how to use the product, asked to practice using it for 7 days, and return to the study center for their next visit.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Other: Questionnaire Administration; Ancillary studies; Other: Electronic Cigarette; Receive different type of ENDS product at each visit; Other Names: e-Cigarette; Electronic Nicotine Delivery System; Other: Electronic Cigarette; Receive BLU e-cigarette ENDS product; Other Names: e-Cigarette; Electronic Nicotine Delivery System

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine Levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes	The maximum concentration of nicotine in plasma (Cmax) will be determined for each product.	Up to 1 year
Levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes	Time to maximum concentration (Tmax) will be determined for each product .	Up to 1 year
Levels of nicotine effectively delivered by various types and brands of ENDS to the bloodstream and compare them to levels delivered from conventional cigarettes	Area under the plasma concentration versus time curve (AUC) will be determined for each product.	up to 1 year
Changes in withdrawal symptoms	Will be measured with Minnesota Withdrawal Scale	up to 1 year
Subjective nicotine effect will be analyzed	Will be measured with Drug Effect Questionnaire	up to 1 year
Changes in feelings and emotions	Will be measured with The Positive Negative Affect Scale	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amounts of nicotine present in various brands and types of ENDS (Study 3)	Nicotine content (mean, median, minimum and maximum) will be determined for each product	Up to 1 year
Nicotine yields in vapors from various types of ENDS under laboratory conditions (Study 4)	Nicotine yield in vapor will be determined for each product.	Up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum concentration of nicotine in plasma (Cmax) (Study 1 and Study 2)	Cmax will be analyzed using a repeated measures analysis of variance, including terms for gender , race and order of treatment	2 hours post using ENDS product
The maximum concentration of nicotine in the area under the plasma concentration - time curve from 0 to 90 minutes (AUC)	AUC will be analyzed using a repeated measures analysis of variance, including terms for gender, race and order of treatment.	2 hours post using ENDS product
The time to maximum concentration of nicotine in plasma (tmax)	tmax will be analyzed using a repeated measures analysis of variance, including terms for gender , race and order of treatment	2 hours post using ENDS product
Estimated puff volume	Puff volume as determined with Cress Micro monitors	2 hours post using ENDS product
Estimated puff duration	Puff duration as determined with Cress Micro monitors	2 hours post using ENDS product

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Institute on Drug Abuse (NIDA); National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Voos N, Smith D, Kaiser L, Mahoney MC, Bradizza CM, Kozlowski LT, Benowitz NL, O'Connor RJ, Goniewicz ML. Effect of e-cigarette flavors on nicotine delivery and puffing topography: results from a randomized clinical trial of daily smokers. Psychopharmacology (Berl). 2020 Feb;237(2):491-502. doi: 10.1007/s00213-019-05386-x. Epub 2019 Nov 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2016
• Primary Completion (Actual): June 6, 2018
• Study Completion (Actual): June 6, 2018

Study Registration Dates

• First Submitted: August 6, 2015
• First Submitted That Met QC Criteria: October 13, 2015
• First Posted (Estimate): October 15, 2015

Study Record Updates

• Last Update Posted (Actual): June 12, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: I 257514 (Other Identifier: Roswell Park Cancer Institute); P30CA016056 (U.S. NIH Grant/Contract); NCI-2015-01187 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01DA037446 (U.S. NIH Grant/Contract)