Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids, SALTVAPE Study

NCT ID: NCT04231539

Last Updated: 2025-10-31

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-18

Study Completion Date

2024-07-10

Brief Summary

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This trial studies activity of time (pharmacokinetics), subjective effects, and abuse liability of nicotine salt-based vaping products with tobacco or e-liquids. This study aims to determine and compare the levels of nicotine delivered to the bloodstream from nicotine salt and free-base nicotine e-liquid solutions.

Detailed Description

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PRIMARY OBJECTIVES:

I. To determine the effect of nicotine salt (nicotine benzoate) and free-base nicotine in different flavored e-liquid solutions on puffing behaviors and systemic exposure to nicotine from electronic nicotine delivery systems (ENDS) by:

Ia. Assessing short-term effects on nicotine cravings, withdrawal, and satisfaction from single use of ENDS refilled with flavored nicotine salt or flavored free-base nicotine solutions with two different flavors (tobacco or unflavored) in current daily ENDS users following an overnight fast.

Ib. Comparing users' perceptions and preferences towards inhaling vapors containing nicotine salt (nicotine benzoate) or freebase nicotine with two different flavors (tobacco and unflavored) versus their regular brand.

II. This project provides important information on whether the pharmacokinetics of nicotine delivery differ between salt and free-base forms of e-liquid of equivalent nominal concentration using the same device, and whether the previously observed effects of flavors on subjective effects differ between salt and free-base forms.

III. Determine whether maximum concentration of nicotine in plasma (Cmax) or time to maximum concentration (Tmax) differ between free-base and salt-based versions of the same liquid, controlling for flavoring and nominal nicotine concentration \[main effect of salt\].

IV. Determine whether the effect of flavoring on subjective effects (e.g., harshness, liking) differs between matched free-base and salt-based e-liquids \[flavor X salt interaction\].

EXPLORATORY OBJECTIVE:

I. Examine effects of salt and flavoring on abuse liability using the Experimental Tobacco Marketplace (ETM).

OUTLINE:

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours, 5-7 days apart. During each session, participants take 20 puffs over 10 minutes (one puff every 30 seconds) of vaporizer filled with freebased nicotine electronic (e)-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored, or salt-based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Conditions

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Nicotine Dependence

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

The participant and researcher will be blinded to solution flavor and nicotine concentrates.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Product Sequence D

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product Sequence A then B then C

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Product sequence B then C then A then D

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence D then B then A then C

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence C then D then B then A

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence A then C

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Product sequence D then C then B then A

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence A then D then B then C

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence D then A then C then B

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence C then D then A then B

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence A then C then D then B

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product Sequence A then B then D then C

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence B then A then D thn C

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Product sequence B then D then C then A

After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored or salt based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Group Type EXPERIMENTAL

Nicotine

Intervention Type DRUG

Vape Free-Low nicotine unflavored

Vaporizer Device

Intervention Type DEVICE

Take puffs from vaporizer filled with different flavors

Salt-HIgh Nicotine Unflavored (Product B)

Intervention Type DRUG

Vape Salt-High nicotine unflavored

Free-Low Nicotine Tobacco Flavored (Product C)

Intervention Type DRUG

Vape Free-Low Nicotine Tobacco

Salt-High Nicotine Tobacco Flavored (Product D)

Intervention Type DRUG

Vape Salt-High Tobacco

Interventions

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Nicotine

Vape Free-Low nicotine unflavored

Intervention Type DRUG

Vaporizer Device

Take puffs from vaporizer filled with different flavors

Intervention Type DEVICE

Salt-HIgh Nicotine Unflavored (Product B)

Vape Salt-High nicotine unflavored

Intervention Type DRUG

Free-Low Nicotine Tobacco Flavored (Product C)

Vape Free-Low Nicotine Tobacco

Intervention Type DRUG

Salt-High Nicotine Tobacco Flavored (Product D)

Vape Salt-High Tobacco

Intervention Type DRUG

Other Intervention Names

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Free-Low Nicotine Unflavored (Product A) NIC Vaporizer

Eligibility Criteria

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Inclusion Criteria

* Willingness to abstain from using ENDS product for 8-10 hours (overnight abstinence) prior to study visits
* Current daily ENDS user as determined by

* Has used ENDS product every day for the past 6 months (by history)
* Has used ENDS product or e-liquid containing nicotine (by history)
* Participant or legal representative must understand the investigational nature of this study and sign and Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

* Smoked cigarettes in the past 7 days
* Currently smokes \>= 5 cigarettes per month
* Unstable medical conditions (such as unstable heart disease, uncontrolled hypertension, thyroid disease, diabetes, renal or liver impairment, or glaucoma) 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)
* History of serious side effects from nicotine or from any nicotine replacement therapies
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or nursing females
* Concurrent participation in another clinical trial
* Unwilling or unable to follow protocol requirements
* Any condition which in the investigator's opinion deems the participant an unsuitable candidate
Minimum Eligible Age

21 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amanda Quisenberry

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

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Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2019-07370

Identifier Type: REGISTRY

Identifier Source: secondary_id

I 475819

Identifier Type: OTHER

Identifier Source: secondary_id

U54CA228110

Identifier Type: NIH

Identifier Source: secondary_id

View Link

I 475819

Identifier Type: -

Identifier Source: org_study_id

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