Nicotine Regulation for Dual Users of E-cigarettes and Cigarettes

Phase 2

Recruiting

• Conditions: Tobacco Use Disorder
• Interventions: Other: Varying the nicotine content of cigarettes; Other: Varying the nicotine content of e-cigarettes

• Registration Number: NCT06614504
• Lead Sponsor: University of Vermont

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 exclusive smokers respond to very low nicotine content (VLNC) cigarettes with reductions in smoking, demand, and dependence. However, nicotine reduction RCTs to date have excluded regular e-cigarette users 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. We propose 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. It is innovative because it is, to our knowledge, the first RCT of a nicotine-limiting standard among the growing population of US adults who use multiple tobacco products. Finally, it is programmatic as it builds upon a decade of nicotine reduction research that we have conducted. Overall, this trial has the potential to provide FDA CTP with evidence on an understudied population important to its regulatory responsibilities.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-23
• Study First Submitted QC: 2024-09-23
• Study First Posted: 2024-09-26
• Study Start: 2024-11-01
• Last Update Submitted: 2025-01-07
• Last Update Posted: 2025-01-09
• Primary Completion: 2028-08-31
• Study Completion: 2028-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 308

Inclusion Criteria

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

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
RC 1 + REC 1	Varying the nicotine content of cigarettes	Research cigarettes #1 plus research e-cigarettes #1
RC 1 + REC 1	Varying the nicotine content of e-cigarettes	Research cigarettes #1 plus research e-cigarettes #1
RC 1 + REC 2	Varying the nicotine content of cigarettes	Research cigarettes #1 plus research e-cigarettes #2
RC 1 + REC 2	Varying the nicotine content of e-cigarettes	Research cigarettes #1 plus research e-cigarettes #2
RC 2 + REC 1	Varying the nicotine content of cigarettes	Research cigarettes #2 plus research cigarettes #1
RC 2 + REC 1	Varying the nicotine content of e-cigarettes	Research cigarettes #2 plus research cigarettes #1
RC 2 + REC 2	Varying the nicotine content of cigarettes	Research cigarettes #2 + research e-cigarettes #2
RC 2 + REC 2	Varying the nicotine content of e-cigarettes	Research cigarettes #2 + research e-cigarettes #2

Primary Outcome Measures

Name	Time	Method
Number of cigarettes smoked per day	12 weeks

Trial Locations

Locations (2)

University of Vermont; 🇺🇸 Burlington, Vermont, United States

Brown University; 🇺🇸 Providence, Rhode Island, United States