Nicotine Regulation for Dual Users of E-cigarettes and Cigarettes

NCT06614504 | Recruiting Phase 2 DMC

• 1 other identifier: R01DA059562
• Study Type: interventional
• Target: 308
• Locations: 1 country
• Sites: 2

Brief Summary

Cigarette smoking remains the leading cause of preventable morbidity and mortality in the US. Use of multiple tobacco products is becoming increasingly prevalent, with dual use of e-cigarettes and cigarettes representing the most common combination. Though e-cigarettes are not without risk, completely switching from cigarettes to e-cigarettes likely reduces risk for tobacco-related harm. However, many established dual users maintain long-term smoking and the majority who use e-cigarettes non-daily are at an even greater risk for prolonged smoking than exclusive cigarette smokers. The Food and Drug Administration Center for Tobacco Products (FDA CTP) has announced plans to implement a nicotine-limiting product standard, capping the nicotine in cigarettes at a minimally or non-addictive level. Randomized controlled trials (RCTs) demonstrate that adults who exclusively smoke cigarettes respond to very low nicotine content (VLNC) cigarettes with reductions in smoking, demand, and dependence. However, nicotine reduction RCTs to date have excluded people who regularly use e-cigarettes and therefore it remains unclear how a nicotine-limiting standard for cigarettes would affect smoking among dual users. Given the potential substitutability of e-cigarettes for cigarettes, reducing the nicotine in cigarettes could promote a transition to exclusive e-cigarette use among dual users unable to completely quit nicotine, but only if sufficiently appealing e-cigarettes remain available. E-cigarettes containing 5% nicotine-salt solution are currently most popular in the US, but policy makers have proposed restricting e-cigarettes to ≤ 2% nicotine to curb youth e-cigarette use, and several states have already set limits to reduce nicotine in e-cigarettes. Prior laboratory studies indicate that higher vs lower nicotine e-cigarettes serve as better substitutes for cigarettes among adult dual users. As such, a restriction on e-cigarette nicotine concentration could undermine the potential for e-cigarettes to substitute for cigarettes and diminish the benefits of a nicotine-limiting standard for cigarettes among dual users. This study is a 12-week double-blind 2 cigarette level (Normal Nicotine vs Very Low Nicotine) x 2 e-cigarette level (High Nicotine vs Low Nicotine) between-subjects factorial trial to investigate how a nicotine-limiting standard for cigarettes affects adult dual users and whether these effects are impacted by constraints on e-cigarette nicotine concentration. Outcome measures include cigarettes per day, cigarette dependence, and toxicant exposure. The research is highly relevant to FDA CTP domains of Addiction and Behavior because it will test whether reducing the nicotine content of cigarettes reduces smoking and dependence, and whether these effects are moderated by the availability of high vs low nicotine e-cigarettes.

Conditions

Tobacco Use Disorder

Keywords

Cigarettes; E-cigarettes

Outcome Measures

Primary Outcomes (1)

• Number of cigarettes smoked per day

  12 weeks

Study Arms (4)

RC 1 + REC 1

EXPERIMENTAL

Research cigarettes #1 plus research e-cigarettes #1

Other: Varying the nicotine content of cigarettes; Other: Varying the nicotine content of e-cigarettes

RC 1 + REC 2

EXPERIMENTAL

Research cigarettes #1 plus research e-cigarettes #2

Other: Varying the nicotine content of cigarettes; Other: Varying the nicotine content of e-cigarettes

RC 2 + REC 1

EXPERIMENTAL

Research cigarettes #2 plus research cigarettes #1

Other: Varying the nicotine content of cigarettes; Other: Varying the nicotine content of e-cigarettes

RC 2 + REC 2

EXPERIMENTAL

Research cigarettes #2 + research e-cigarettes #2

Other: Varying the nicotine content of cigarettes; Other: Varying the nicotine content of e-cigarettes

Interventions

Varying the nicotine content of cigarettes OTHER

Altering the nicotine content of the tobacco research cigarettes

Also known as: Comparing normal nicotine content (RC 1) to very low nicotine content (RC 2)

RC 1 + REC 1; RC 1 + REC 2; RC 2 + REC 1; RC 2 + REC 2

Varying the nicotine content of e-cigarettes OTHER

Altering the nicotine content of the research e-cigarettes

Also known as: Comparing high nicotine content (REC 1) to low nicotine content (REC 2)

RC 1 + REC 1; RC 1 + REC 2; RC 2 + REC 1; RC 2 + REC 2

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Regular use of tobacco
• year of age or older
• Speak, comprehend and read English well enough to complete study procedures

You may not qualify if:

• Pregnant, trying to become pregnant, or nursing
• Under the age of 21
• Health conditions that could undermine ability to complete the study

Sponsors & Collaborators

• University of Vermont: lead

Study Sites (2)

Brown University

Providence, Rhode Island, 02903, United States

RECRUITING

University of Vermont

Burlington, Vermont, 05405, United States

RECRUITING

MeSH Terms

Conditions

Tobacco Use Disorder; Vaping

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior

Study Officials

• Elias Klemperer, PhD

  University of Vermont

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily Booth

CONTACT

802-656-1641; emily.booth@med.uvm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 2x2 factorial randomized controlled trial

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: September 26, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): September 30, 2028
• Last Updated: June 27, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (2)