Nicotine Regulation for Dual Users of E-cigarettes and Cigarettes (RDEC)

June 23, 2025 updated by: Elias Klemperer, University of Vermont

A Randomized Controlled Trial of Reduced Nicotine Cigarettes and E-cigarettes Among Dual Users

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

308

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Brown University
        • Contact:
        • Principal Investigator:
          • Jennifer Tidey, PhD
    • Vermont
      • Burlington, Vermont, United States, 05405

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RC 1 + REC 1
Research cigarettes #1 plus research e-cigarettes #1
Other: Varying the nicotine content of cigarettes
Altering the nicotine content of the tobacco research cigarettes
Other Names:
  • Comparing normal nicotine content (RC 1) to very low nicotine content (RC 2)
Other: Varying the nicotine content of e-cigarettes
Altering the nicotine content of the research e-cigarettes
Other Names:
  • Comparing high nicotine content (REC 1) to low nicotine content (REC 2)
Experimental: RC 1 + REC 2
Research cigarettes #1 plus research e-cigarettes #2
Other: Varying the nicotine content of cigarettes
Altering the nicotine content of the tobacco research cigarettes
Other Names:
  • Comparing normal nicotine content (RC 1) to very low nicotine content (RC 2)
Other: Varying the nicotine content of e-cigarettes
Altering the nicotine content of the research e-cigarettes
Other Names:
  • Comparing high nicotine content (REC 1) to low nicotine content (REC 2)
Experimental: RC 2 + REC 1
Research cigarettes #2 plus research cigarettes #1
Other: Varying the nicotine content of cigarettes
Altering the nicotine content of the tobacco research cigarettes
Other Names:
  • Comparing normal nicotine content (RC 1) to very low nicotine content (RC 2)
Other: Varying the nicotine content of e-cigarettes
Altering the nicotine content of the research e-cigarettes
Other Names:
  • Comparing high nicotine content (REC 1) to low nicotine content (REC 2)
Experimental: RC 2 + REC 2
Research cigarettes #2 + research e-cigarettes #2
Other: Varying the nicotine content of cigarettes
Altering the nicotine content of the tobacco research cigarettes
Other Names:
  • Comparing normal nicotine content (RC 1) to very low nicotine content (RC 2)
Other: Varying the nicotine content of e-cigarettes
Altering the nicotine content of the research e-cigarettes
Other Names:
  • Comparing high nicotine content (REC 1) to low nicotine content (REC 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of cigarettes smoked per day
Time Frame: 12 weeks
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vermont

Investigators

  • Principal Investigator: Elias Klemperer, PhD, University of Vermont

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

August 31, 2028

Study Completion (Estimated)

September 30, 2028

Study Registration Dates

First Submitted

September 23, 2024

First Submitted That Met QC Criteria

September 23, 2024

First Posted (Actual)

September 26, 2024

Study Record Updates

Last Update Posted (Actual)

June 27, 2025

Last Update Submitted That Met QC Criteria

June 23, 2025

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R01DA059562 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be made available once we have published the results of the parent trials and manuscripts based on secondary analyses of those data, which we anticipate taking approximately three years.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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