Do Flavors Increase the Addiction Potential of Nicotine?

• ClinicalTrials.gov Identifier: NCT04696380
• Recruitment Status: Recruiting
• First Posted: January 6, 2021
• Last Update Posted: March 29, 2021
• Sponsor: University of Vermont
• Information provided by (Responsible Party): John Hughes, University of Vermont

Study Description

Brief Summary:

The FDA has concluded that flavors (e.g. menthol) are associated with greater addiction potential in tobacco cigarettes (Gottlieb March 13, 2019). Whether the same is true for e-cigarettes and non-menthol flavors is unclear and our study should help answer this question.

Our major hypothesis is that the pharmacological effect of nicotine to induce addiction will be greater with use of a preferred e-cigarette flavor than with use of a non-preferred flavor. The pharmacological effect will be measured by how much a larger nicotine dose increases addiction potential compared to a smaller dose.

Condition or disease	Intervention/treatment	Phase
Nicotine Dependence	Drug: Nicotine; Device: JUUL e-cigarette	Phase 2

Detailed Description:

Study Design:

Fifteen participants who currently use e-cigarettes weekly and who use or do not use tobacco cigarettes will enter a remote session study. Participants will be asked to abstain from all nicotine/tobacco products, non-nicotine electronic cigarettes, and THC containing products for 16 hours prior to four experimental sessions and will be tested in a 2x2 within-participants design with four conditions: 1) low nicotine dose (3%)/non-preferred flavor, 2) low dose/preferred flavor, 3) high dose (5%)/non-preferred flavor, and 4) high dose/preferred flavor. Order of testing will be randomized. Participants and experimenters will be blind to dose. The major outcomes will be subjective effects, e.g. liking and tests of reinforcement (choice procedures). We will require 16 hours of abstinence prior to each remote experimental session to increase the sensitivity to nicotine effects.

The consent process, experimental sessions and data collection will all be done remotely using a secure video platform. The only interaction between participants and research staff will be the curbside pick-up of study products, which will follow social distancing and mask guidelines. Participants will pick up study JUUL pods curb-side at the University of Vermont before their baseline videoconference session. Participants will be required to conduct all videoconference sessions in a place where they can legally use their JUUL.

The consent videoconference session will be conducted prior to the baseline and four experimental sessions. Participants will be assessed for COVID-19 and E-cigarette or Vaping Product Use-Associated Lung Injury (EVALI) symptoms prior to the curbside pick-up and at the start of the 5 videoconference sessions in which they will be asked to vape. During the baseline session, participants will complete a baseline questionnaire via online survey and then answer a series of questions about nicotine dependence and how many JUUL pods they would purchase at varying prices. Participants will then sample the two flavors available for JUUL -Virginia Tobacco and Menthol- using their own JUUL device. Research staff will ask participants to rate the pleasantness of each flavor and, after they have tried the flavors, participants will rank order their flavor preferences to determine their preferred flavor of the two. Finally, participants will be trained in the puffing protocol to be used in the experimental sessions.

During each experimental videoconference session, participants will report on their recent e-cigarette and tobacco product use at the start of each videoconference testing session. Those reporting non-abstinence will have their videoconference session rescheduled. During the videoconference testing sessions participants will be asked to puff either tobacco flavor 3% nicotine, tobacco flavor 5% nicotine, menthol flavor 3% nicotine, or menthol flavor 5% nicotine. After each puffing bout within each session, they will answer questions about about e-cigarette effects, e-cigarette liking and wanting, like/dislike of e-cigarette taste and e-cigarette intensity. At the end of each session, they will be asked how many JUUL pods they would purchase at varying prices.

Adverse events will be collected at the end of each videoconference session by the research assistant, who will consult with the study licensed medical provider.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: Do Flavors Increase the Addiction Potential of Nicotine?: A Pilot Laboratory Study
• Actual Study Start Date: March 1, 2021
• Estimated Primary Completion Date: August 31, 2021
• Estimated Study Completion Date: August 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: High nicotine, preferred flavor; Participants will sample their preferred flavored JUUL e-cigarette at 5% nicotine strength.	Drug: Nicotine; Participants will sample high vs low nicotine.; Device: JUUL e-cigarette; Participants will sample preferred vs non-preferred JUUL flavors.
Experimental: High nicotine, non-preferred flavor; Participants will sample their non-preferred flavored JUUL e-cigarette at 5% nicotine strength.	Drug: Nicotine; Participants will sample high vs low nicotine.; Device: JUUL e-cigarette; Participants will sample preferred vs non-preferred JUUL flavors.
Experimental: Low nicotine, preferred flavor; Participants will sample their preferred flavored JUUL e-cigarette at 3% nicotine strength.	Drug: Nicotine; Participants will sample high vs low nicotine.; Device: JUUL e-cigarette; Participants will sample preferred vs non-preferred JUUL flavors.
Experimental: Low nicotine, non-preferred flavor; Participants will sample their non-preferred flavored JUUL e-cigarette at 3% nicotine strength.	Drug: Nicotine; Participants will sample high vs low nicotine.; Device: JUUL e-cigarette; Participants will sample preferred vs non-preferred JUUL flavors.

Outcome Measures

Primary Outcome Measures :

1. Liking and wanting nicotine [ Time Frame: 2 weeks ]
   Average of "I feel good e-cigarette effects", "I want more of that e-cigarette I received", "I feel the e-cigarette strength" and "I like the e-cigarette effect" on a 0-100mm scale from "not at all" (0) to "extremely" (100).
2. E-cigarette purchase task [ Time Frame: 2 weeks ]
   This is a modification of the Cigarette Purchase Task that asks how much users would spend to obtain their usual amount of e-liquids to use.
3. E-cigarette and tobacco cigarette craving [ Time Frame: 2 weeks ]
   This is a revision of the brief version Questionnaire of Smoking Urges that asks about the presence of urges for e-cigarettes and tobacco cigarettes (0-4 scale, 0= not at all and 4= extremely) and strength of urges (1-5 scale, 1=slight and 5= extremely strong).
4. Modified Drug Effect Questionnaire [ Time Frame: 2 weeks ]
   Modified version of the Drug Effects Questionnaire where participants rate acute responses to the e-cigarette drug effects on a 0-100 mm scale, from "not at all" (0) to "extremely" (100).
5. Modified Labeled Hedonic Scale [ Time Frame: 2 weeks ]
   1 item about like/dislike of the e-cigarette taste using a modified version of the Labeled Hedonic Scale, a category ratio scale that ranges from -100 (most disliked) to 100 (most liked).
6. Modified Labeled Magnitude Scale [ Time Frame: 2 weeks ]
   1 item about e-cigarette taste intensity using a modified version of the Labeled Magnitude Scale, which is a category ratio scale with 7 semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", with responses coded on a 0-100 scale (0= no sensation, 100= strongest imaginable).

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria:

• 21 years or older
• comfortable reading and writing English
• own a JUUL brand e-cigarette they have used at least 10 times in the past 30 days
• use JUUL e-cigarettes and JUUL pods with 5% nicotine
• used e-cigarettes on 4+ days a week in the last 30 days
• use or do not use tobacco cigarettes
• do not plan to quit e-cigarettes in the next 30 days
• non-pregnant females verified by pregnancy test
• access to the internet in a location where they could join a videoconference call and legally use their JUUL.
• Reside in VT

Contacts and Locations

Contacts

Contact: research specialist; 802-656-9358; ecigarette.study@uvm.edu

Locations

United States, Vermont

University of Vermont; Recruiting

Burlington, Vermont, United States, 05401

Contact: John Hughes, MD 802-656-9610 john.hughes@uvm.edu

Principal Investigator: John Hughes, MD

Sponsors and Collaborators

University of Vermont

Investigators

• Principal Investigator: John R Hughes, MD; University of Vermont

More Information

• Responsible Party: John Hughes, Professor, University of Vermont
• ClinicalTrials.gov Identifier: NCT04696380
• Other Study ID Numbers: CHRMS 00000555
• First Posted: January 6, 2021
• Last Update Posted: March 29, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Tobacco Use Disorder; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Nicotine; Ganglionic Stimulants; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action