NCT04084210

Brief Summary

The goal of this research is to understand the potential impact of two new FDA strategies to ensure the availability of safer Alternative Nicotine Delivery Systems (ANDS) and to reduce the nicotine content in combustible cigarettes to non-addictive levels. Specifically, this research will examine how well ANDS and very low nicotine cigarettes (VLNCs) can work alone or in combination with the current strategy of providing a safe source of nicotine via nicotine replacement medications to reduce use of combustible cigarettes, in real-world settings. The investigators will enroll 180 daily adult smokers who are not planning to quit smoking within the next 30 days into this mixed design study. Participants will be randomly assigned to one of three levels of the between-subjects factor: 1) VLNC cigarettes; 2) Juul e-cigarettes (with nicotine); or 3) no alternative product. Participants receiving an alternative product (VLNC or e-cigarettes) will be asked to use it for 4 weeks (Weeks 1 through 4). During Weeks 2 and 4 all participants will be asked to switch from their cigarettes to use only study products (i.e., Juul e-cigarettes, VLNCs, or no alternative product) and to use either an active nicotine or placebo patch (the within-subjects factor), provided in double-blind fashion and counterbalanced order. During Weeks 1 through 4, participants will use a smartphone to record, in the moment, each time they use their own cigarettes or any alternative product. For a random daily subset of use events, participants will complete additional questions about the internal and external context of their use (e.g., affect, any restrictions on smoking) and their response to use (e.g., withdrawal alleviation, taste, satisfaction). Using these data, the investigators will also examine the effects of these products on the rewarding value of smoking and possible mechanisms driving such behavior (e.g., withdrawal alleviation, satisfaction, taste). This research will provide critical information regarding the potential impact of providing cigarettes with non-addictive levels of nicotine and safe ANDS, with or without nicotine replacement, in real-world settings on smokers' use of their usual cigarettes and other outcomes. Information on the short-term effects of products that could be accessible in the future will provide data that could inform regulatory policy decisions regarding the public health impact of safe ANDS and non-addictive cigarettes.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
209

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2020

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 5, 2019

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 10, 2019

Completed
1 year until next milestone

Study Start

First participant enrolled

September 9, 2020

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 23, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 23, 2022

Completed
1 year until next milestone

Results Posted

Study results publicly available

May 25, 2023

Completed
Last Updated

May 25, 2023

Status Verified

May 1, 2023

Enrollment Period

1.7 years

First QC Date

September 5, 2019

Results QC Date

February 2, 2023

Last Update Submit

May 2, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • Mean Number of Conventional Cigarettes Smoked During Each Switch Week

    The mean number of conventional cigarettes smoked during each Switch Week will be used as a measure for conventional cigarette usage.

    During the two 1-week switching periods

Secondary Outcomes (1)

  • Mean Number of VLNCs Smoked or Vape Events Per Day Reported During Each Switch Week

    During the two 1-week switching periods

Study Arms (6)

Juul + Active Patch in Wk 1 and Placebo Patch in Wk 2

ACTIVE COMPARATOR

Participants will be given Juul e-cigarettes for four weeks; in Switch Week 1, participants also will use active nicotine patches; in Switch Week 2, participants will use placebo patches.

Device: Juul Electronic cigaretteDrug: Active Nicotine PatchOther: Placebo Patch

Juul + Placebo Patch in Wk 1 and Active Patch in Wk 2

ACTIVE COMPARATOR

Participants will be given Juul e-cigarettes for four weeks; in Switch Week 1, participants also will use placebo patches; in Switch Week 2, participants will use active nicotine patches.

Device: Juul Electronic cigaretteDrug: Active Nicotine PatchOther: Placebo Patch

VLNC + Active Patch in Wk 1 and Placebo Patch in Wk 2

ACTIVE COMPARATOR

Participants will be given very low nicotine cigarettes (VLNCs) for four weeks; in Switch Week 1, participants also will use active nicotine patches; in Switch Week 2, participants will use placebo patches.

Other: Very Low Nicotine CigarettesDrug: Active Nicotine PatchOther: Placebo Patch

VLNC + Placebo Patch in Wk 1 and Active Patch in Wk 2

ACTIVE COMPARATOR

Participants will be given very low nicotine cigarettes (VLNCs) for four weeks; in Switch Week 1, participants also will use placebo patches; in Switch Week 2, participants will use active nicotine patches.

Other: Very Low Nicotine CigarettesDrug: Active Nicotine PatchOther: Placebo Patch

No Product + Active Patch in Wk 1 and Placebo Patch in Wk 2

OTHER

Participants will be given no alternative nicotine delivery products but in Switch Week 1, participants will use active nicotine patches; in Switch Week 2, participants will use placebo patches.

Drug: Active Nicotine PatchOther: Placebo Patch

No Product + Placebo Patch in Wk 1 and Active Patch in Wk 2

OTHER

Participants will be given no alternative nicotine delivery products for two weeks but in Switch Week 1 participants will use placebo patches; in Switch Week 2, participants will use active nicotine patches.

Drug: Active Nicotine PatchOther: Placebo Patch

Interventions

The juul e-cigarette pods contain 0.7 ml nicotine by volume / 5% nicotine by weight.

Also known as: Juul
Juul + Active Patch in Wk 1 and Placebo Patch in Wk 2Juul + Placebo Patch in Wk 1 and Active Patch in Wk 2

These very low nicotine cigarettes (VLNCs) consist of reduced nicotine cigarettes containing 0.03 mg of nicotine; these VLNCs were obtained from National Institute on Drug Abuse (NIDA's) Drug Supply Program (NOT-DA-14-004).

Also known as: VLNC
VLNC + Active Patch in Wk 1 and Placebo Patch in Wk 2VLNC + Placebo Patch in Wk 1 and Active Patch in Wk 2

Active nicotine patches, with dosing based on the package insert (\>10 cigs/day = 21 mg patch and \<11 cigs/day = 14 mg patches).

Also known as: Nicotine Patch
Juul + Active Patch in Wk 1 and Placebo Patch in Wk 2Juul + Placebo Patch in Wk 1 and Active Patch in Wk 2No Product + Active Patch in Wk 1 and Placebo Patch in Wk 2No Product + Placebo Patch in Wk 1 and Active Patch in Wk 2VLNC + Active Patch in Wk 1 and Placebo Patch in Wk 2VLNC + Placebo Patch in Wk 1 and Active Patch in Wk 2

Placebo patch containing no nicotine.

Juul + Active Patch in Wk 1 and Placebo Patch in Wk 2Juul + Placebo Patch in Wk 1 and Active Patch in Wk 2No Product + Active Patch in Wk 1 and Placebo Patch in Wk 2No Product + Placebo Patch in Wk 1 and Active Patch in Wk 2VLNC + Active Patch in Wk 1 and Placebo Patch in Wk 2VLNC + Placebo Patch in Wk 1 and Active Patch in Wk 2

Eligibility Criteria

Age21 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • smoking \>4 cigarettes/day for the previous 6 months
  • able to read, write, and speak English
  • no plans to quit smoking in the next 30 days
  • not currently taking smoking cessation medication
  • willing and medically able to use nicotine patches
  • exhaled carbon monoxide (CO) \> 6 ppm.

You may not qualify if:

  • currently in treatment for psychosis or bipolar disorder
  • e-cigarette use within the last month
  • currently pregnant or breastfeeding.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

University of Wisconsin Center for Tobacco Research and Intervention

Madison, Wisconsin, 53711, United States

Location

UW Center for Tobacco Research and Intervention

Milwaukee, Wisconsin, 53233, United States

Location

Related Publications (1)

  • Piper ME, Kaye JT, Piasecki TM, Yang JJ, Buu A. Cannabis use among adults who smoke tobacco: Relations with switching from combusted cigarettes to e-cigarettes or very low nicotine cigarettes. Drug Alcohol Depend. 2025 Oct 1;275:112821. doi: 10.1016/j.drugalcdep.2025.112821. Epub 2025 Aug 6.

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Therapeutics

Results Point of Contact

Title
Megan Piper, PhD, Director of Research Professor
Organization
University of Wisconsin- Madison

Study Officials

  • Megan E Piper, PhD

    University of Wisconsin, Madison

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Participants will be randomly assigned to Juul, Very Low Nicotine Cigarette, or No Product with no masking of product type. However, participants will be randomly assigned to receive either placebo or active nicotine patch with masking regarding placebo vs active patch.
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: For this mixed design study, 180 daily adult smokers who are not planning to quit smoking will be randomly assigned to one of three levels of the between-subjects factor: 1) VLNCs; 2) Juul e-cigarettes; or 3) no alternative product. During two different weeks, participants will be asked to switch from their usual cigarettes and use only study products. They will also be asked to use either an active nicotine or placebo patch (the within-subjects factor), provided in double-blind fashion and counterbalanced order. It should be noted that there were no significant within-subject effects (i.e. comparing Juul + Active Patch in Wk 1 and Placebo Patch in Wk 2 vs. JUUL + Placebo Patch in Wk 1 then Active Patch in Wk 2 yielded no significant differences) therefore results are presented as a 3-group parallel design (i.e. Juul + Active vs. Placebo Patch, VLNC + Active vs. Placebo Patch, No Product + Active vs. Placebo Patch).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 5, 2019

First Posted

September 10, 2019

Study Start

September 9, 2020

Primary Completion

May 23, 2022

Study Completion

May 23, 2022

Last Updated

May 25, 2023

Results First Posted

May 25, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will share

We will make the set of final de-identified datasets available in encrypted standard file formats or secure File Transfer Protocol (FTP) transmission by request from other researchers in a timely manner (no later than the acceptance for publication of the main findings from the final dataset).

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
After the publication of the main findings
Access Criteria
Approval of a data request by the investigators

Locations