Evidence map›Paper›PMID 40628358›Full record

Trial reportPreventive medicine2025

E-cigarette use frequency mediates effects in three randomized controlled trials of reduced nicotine cigarettes with tobacco vs preferred flavor e-cigarettes in high-risk populations in the U.S.

Elias M Klemperer, Michael J DeSarno, Jennifer W Tidey, Diann E Gaalema, Katya A Nolder, Marc Jerome P Feinstein, Rhiannon C Wiley, Stephen T Higgins

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Preventive medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Electronic cigarettes for smoking cessation.The Cochrane database of systematic reviews · 2026
    Pooled it
  2. Trial
  3. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Elias M KlempererUVM Tobacco Center of Regulatory Science, University of Vermont, Burlington, VT, United States of America. Electronic address: elias.klemperer@med.uvm.edu.
Michael J DeSarnoUVM Tobacco Center of Regulatory Science, University of Vermont, Burlington, VT, United States of America.
Jennifer W TideyCenter for Alcohol and Addiction Studies, Brown University, Providence, RI, United States of America.
Diann E GaalemaDivision of Cardiovascular Medicine, University of Texas Medical Branch, Galveston, TX, United States of America.
Katya A NolderUVM Tobacco Center of Regulatory Science, University of Vermont, Burlington, VT, United States of America.
Marc Jerome P FeinsteinUVM Tobacco Center of Regulatory Science, University of Vermont, Burlington, VT, United States of America.
Rhiannon C WileyUVM Tobacco Center of Regulatory Science, University of Vermont, Burlington, VT, United States of America.
Stephen T HigginsUVM Tobacco Center of Regulatory Science, University of Vermont, Burlington, VT, United States of America.

Funding

University of Vermont Tobacco Center of Regulatory ScienceU54DA036114 · NIDA · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HIGGINS, STEPHEN T · 2018 to 2022
$19.4M
TRAINING IN BEHAV. PHARMACOLOGY OF HUMAN DRUG DEPENDENCET32DA007242 · NIDA · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI HEIL, SARAH H, HIGGINS, STEPHEN T · 1990 to 2025
$8.2M
Vermont Center on Behavior and HealthP30GM149331 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Stephen T Higgins · 2023 to 2026
$5.6M
A randomized controlled trial of reduced nicotine cigarettes and e-cigarettes among dual usersR01DA059562 · NIDA · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Elias M Klemperer · 2024 to 2026
$2.3M
NIDA NIH HHS R01 DA059562NIDA NIH HHS T32 DA007242NIDA NIH HHS U54 DA036114NIGMS NIH HHS P30 GM149331
6 · The paper itself

Abstract

objectivesThe U.S. Food and Drug Administration is authorized to implement a nicotine-reducing standard to decrease smoking. Three recent trials found switching to very low nicotine content (VLNC) cigarettes produced the greatest reduction in cigarettes/day and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, a tobacco-specific carcinogen) among adults from high-risk populations when participants also received preferred- vs tobacco-flavored e-cigarettes. This pooled secondary analysis investigates e-cigarette use frequency as a mechanism driving these effects.

methodsParticipants (U.S. adults with affective disorders, adults with opioid use disorder, and reproductive-age females with ≤high-school education) were randomized to 16 weeks of VLNC cigarettes with preferred-flavored e-cigarettes selected from eight options (VLNC+PF; n = 84) or VLNC cigarettes with tobacco-flavored e-cigarettes (VLNC+TF; n = 74) from October 2020-November 2023. General linear models explored whether e-cigarette use frequency (days/week) between Weeks 1-15 mediated effects on Week-16 cigarettes/day and NNAL.

resultsParticipants were 40.4 (mean) years old (SD = 11.5), 69.0 % female, 81.0 % white, and smoked 17.3 (mean) cigarettes/day (SD = 9.0) at baseline. The VLNC+PF condition reported more e-cigarette use days/week (LSmean[SEM]): 4.3[±0.4]) than the VLNC+TF condition (LSMean[SEM]: 3.4[±0.5]; F[1151] = 3.9, p < .05) across weeks 1-15. More e-cigarette use days/week predicted greater reductions in mean cigarettes/day (β[SE]: -0.32[±0.05)]; F[1106] = 50.5, p < .01) and NNAL (β[SE]: -0.14[±0.04]; F[1,92] = 12.2, p < .01) at Week-16. E-cigarette use frequency fully mediated the effects of condition on cigarettes/day and partially mediated effects on NNAL.

conclusionsGreater frequency of e-cigarette use was a mechanism by which preferred-flavor e-cigarettes led to reductions in smoking and tobacco-toxicant exposure, demonstrating the potential for appealing e-cigarettes to reduce harm among high-risk populations who smoke.

Indexed as

Electronic Nicotine Delivery SystemsNicotineTobacco ProductsVapingAdultFemaleFlavoring AgentsHumansMaleMiddle AgedUnited StatesFlavoring AgentsNicotineAffective disordersCigarette smokingE-cigarettesEducational attainmentElectronic nicotine delivery systemsFlavored e-cigarettesNicotine product standardNicotine reductionOpioid use disorderWomen

Identifiers

PMID40628358
PMCPMC12291598

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.