Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04084210 |
| Other study ID # |
2019-0252 |
| Secondary ID |
1R01CA239309A534 |
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
September 9, 2020 |
| Est. completion date |
May 23, 2022 |
Study information
| Verified date |
May 2023 |
| Source |
University of Wisconsin, Madison |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
Design and Objective: The primary goal of this research is to assess the ability of
alternative products (VLNCs vs. e-cigs vs. no alternative product; between-subjects factor)
to serve as a substitute for conventional cigarettes and how this is influenced by
steady-state nicotine (nicotine vs. placebo patches; within-subjects factor). In addition,
the investigators will explore the contexts in which participants are and are not able to
switch from their conventional cigarettes. Such contextual information will provide insight
into internal (i.e., withdrawal, expectancies) and external environments (i.e., being around
smokers, smoking restrictions) that promote or interfere with switching behavior. The
investigators will also explore person factors and beliefs that may drive alternative product
use and substitution success. Person factors that may influence use behavior include sex (a
key biological variable), education level, dependence, instrumental smoking motives (e.g.,
smoking for affect regulation, taste, or social experiences), and psychiatric comorbidity.
Beliefs that may influence use behavior include beliefs about the safety and addiction
potential of conventional cigarettes and the alternative products. Understanding the relation
of person factors and beliefs with use behavior could inform regulatory actions related to
product labeling and education. Finally, the investigators will explore potential mechanisms
that might drive use behavior and support substitution.
This research will enroll 180 adult smokers in a mixed design study with a within-subjects
factor (active nicotine patch vs. placebo patch) and a between-subjects factor (alternative
products: VLNCs, e-cigs, or no product). Participants will be randomized to receive either 4
weeks of VLNCs, 4 weeks of e-cigs, or no alternative product. After one week practicing with
the alternative product, participants will complete the first of two 7-day switching trials
during which they will be asked to refrain from smoking their own cigarettes and encouraged
to use the alternative product to which they have been assigned (although the no alternative
product group will not have any other products to use). All participants will be given
patches (active nicotine or placebo, in counterbalanced order) to use during the Switch Week.
After this first Switch Week, participants will smoke normally for one week and then have
their second Switch Week using the other type of patch (active or placebo). Participants will
complete Ecological Momentary Assessments (EMAs) on smartphones at baseline and during the 4
weeks of product use. EMA targets include own cigarette use, alternative product use,
withdrawal symptoms, rewarding value of product use (e.g., taste, buzz), and environmental
and affective context of any tobacco product use. The investigators will then conduct a
3-month follow-up to assess cigarette and e-cig use, risk perceptions, and future use
intentions.
This design addresses the six critical methodological issues for understanding the impact of
alternative products outlined by Villanti et al.: 1) rigorous assessment of the key outcome
(conventional cigarettes smoked); 2) assessment of product use during switching; 3) use of
appropriate control/comparison groups; 4) measurement of product exposure/use that precedes
switching; 5) evaluation of the dose and duration of product exposure/use; and 6) clear
evaluation of the type and quality of the products used (e.g., satisfaction).
Recruitment and Participants: Participants from the greater Madison and Milwaukee, Wisconsin
areas will be recruited via media recruitment methods (i.e., television, newspaper, and
earned media) that have recruited thousands of smokers. Investigators will also use
Internet/Facebook advertisements that have been successful in recent e-cig studies that
recruited 422 smokers willing to provide EMA data during seven 2-week assessment periods over
2 years and 74 dual users willing to reduce combustible cigarette use and switch to using
only e-cigs. Given this, it is feasible to recruit 180 smokers for this study within 18
months.
Procedures and Measures: Interested smokers will complete a phone screen to determine initial
eligibility. Potentially eligible smokers will attend an orientation visit where, after
providing a breath sample to verify eligibility (CO > 6 ppm), they will receive a detailed
description of the study and provide written informed consent, and complete baseline
assessments. At Visit 1, participants will be randomized to receive VLNCs, e-cigs, or no
alternative product and will be trained to use the product. The study database will randomize
participants, stratified by clinic, gender, and race [White vs. Non-White], to enhance
scientific rigor and reproducibility. Participants will be trained to use the smartphone to
complete daily assessments, using the training that was effective in prior research, and will
schedule future study visits. Participants will use their alternative products as they would
like for one week to become comfortable with the product. At Visit 2, participants will
complete assessments, provide a breath sample for CO assessment and a urine sample for
cotinine assessment, receive feedback on their compliance with the smartphone assessments,
and be given study patches to use during Switch Week 1 when they will be asked to abstain
from using their own cigarettes for the week. Participants will then attend a mid-Switch Week
visit (Visit 3) and an end-of-Switch Week visit (Visit 4) to assess biomarkers (a breath
sample for CO assessment and a urine sample for cotinine). At Visit 4, the end of Switch Week
1, participants will be told that they can smoke as usual for a week. Then, at the start of
Switch Week 2 (Visit 5), participants will be given the other type of patch (active or
placebo) and asked to abstain from smoking their own cigarettes for a week. As during the
prior Switch Week, participants will attend visits mid-week and at the end of the week to
assess biomarkers (Visits 6 and 7). The investigators will attempt to schedule appointments
at the same time of day (i.e., within a 2-hour window) for each participant so that there is
consistent time for product use prior to providing the biological samples across study
visits. Participants will complete a follow-up assessment call at 3 months. The baseline
visit will last 2 hours, but subsequent visits will last <30 minutes. Participants will carry
a smartphone to complete EMAs from Orientation through all 4 weeks of product use.
Knowledge to be Gained: The results from this research will provide important insight into
how well very low nicotine cigarettes and e-cigarettes serve as a substitute for conventional
cigarettes and how this is influenced by the presence of steady-state nicotine. Further,
these data will inform scientists and regulators about the potential mechanisms that may
support the use of alternative products. This information will aid scientists and regulatory
bodies in understanding the real-world impact of potential regulatory policies regarding
access to safer nicotine sources and reducing the addiction potential of combustible tobacco
products.
