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CompletedNCT03674970Updated Jan 22, 2021Results posted

Effects of Random Nicotine Delivery on Smoking Cessation

A Phase 1/2 interventional study of Nicotine Film in Smoking Cessation, Cigarette Smoking and Smoking (Tobacco) Addiction, sponsored by Milton S. Hershey Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-01-22.

Sponsored by Milton S. Hershey Medical Center · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
45
Allocation
Randomized
Ages
18 Years to 55 Years
Sex
All
01

Study summary

The objective of this study is to determine whether treatment with random nicotine delivery via a nicotine film both before and after the target quit date will facilitate smoking cessation relative to treatment with steady state delivery or placebo.

The investigators hypothesize that smoking cessation will be greater in subjects assigned to a random nicotine delivery regimen (as compared to those assigned to a steady state or placebo regimen). The nicotine film product is not part of the standard of care and is not available in non-investigational settings in the United States.

Read the detailed description

This project is a prospective parallel-group, randomized, double-blind, placebo-controlled study in which 45 current cigarette smokers who are interested in quitting will be randomly allocated to one of three possible nicotine film treatment regimens:

  1. Random nicotine delivery (a combination of four 0 mg and 4 mg films daily not to exceed three non-consecutive 4 mg films in one day and to maintain an average of 8 mg of nicotine per day through 7 days for 6 weeks total).
  2. Steady state nicotine delivery (2, 2, 2, 2 mg films daily for 6 weeks total)
  3. Placebo delivery (0, 0, 0, 0 mg films daily for 6 weeks total)

Prior to assignment in one of the above treatment groups, all participants will take part in a 1-week baseline period to assess normal smoking behavior and nicotine dependence. Following randomization to their assigned treatment group at Visit 2, participants will be instructed to smoke cigarettes as they feel necessary over the next two weeks while using the nicotine films as directed (i.e., one film every 3-4 hours for a total of four films per day). After two weeks of pre-cessation treatment, participants will be asked completely cease cigarette smoking and to only use their assigned nicotine films as directed. Participants will be supported in their quitting efforts with regular contacts both in person at the Penn State Milton S. Hershey Medical Center and over the phone.

02

Conditions studied

  • Smoking Cessation
  • Cigarette Smoking
  • Smoking (Tobacco) Addiction

Keywords

  • smoking cessation
  • nicotine film
  • nicotine delivery
  • random nicotine delivery
03

In context

Smoking Cessation

350 studies on the registry are indexed under Smoking Cessation; 145 are open to participants now.

This study's enrollment of 45 is below the median of 150 across 326 interventional studies indexed under Smoking Cessation.

Browse Smoking Cessation studies →

Lead sponsor

Milton S. Hershey Medical Center is the lead sponsor of 491 studies on the registry; 59 are open to participants now.

Of its 58 completed or terminated interventional studies of FDA-regulated products, 44 (76%) have results posted.

Browse Milton S. Hershey Medical Center studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Aged 18-55
  • Smoke ≥10 cigarettes/day for at least the past 12 months
  • Exhaled CO measurement ≥6 ppm at baseline visit
  • Interested in completely ceasing cigarette consumption and using a nicotine film product as directed
  • Willing to attend regular visits over a 6-week period (not planning to move, not planning extended vacation, no planned surgeries)
  • Able to read and write in English
  • Able to understand and consent to study procedures

Exclusion criteria

Exclusion Criteria:

  • Unstable or significant medical conditions and conditions such as elevated blood pressure (systolic >159 mmHg or diastolic >99mmHg at baseline), COPD, and those conditions that are likely to affect biomarker data such as kidney or liver disease
  • Individuals with sodium-restricted diet, heart disease, recent heart attack, irregular heartbeat, stomach ulcers, or diabetes as well as those taking prescription medications for depression or asthma as indicated under "Warnings" section on FDA approved NRT Drug Facts Label
  • More than weekly use in the past 3 months of illegal drugs or prescription drugs that are not being used for medically prescribed purposes
  • Use of non-cigarette nicotine delivery product in the prior 7 days (including cigars, pipes, chew, snus, hookah, electronic cigarette and marijuana mixed with tobacco)
  • Use of an FDA approved cessation medication in the past 7 days (any NRT, Chantix, Wellbutrin)
  • Women who are pregnant (verified by urine pregnancy test at baseline visit), trying to become pregnant, or nursing
  • Uncontrolled mental illness or substance abuse or inpatient treatment for these conditions in the past 6 months
  • Any previous adverse reaction to NRT
  • Any other condition, serious illness, or situation that would, in the investigator's opinion, make it unlikely that the participant could comply with the study protocol
  • Other member of household currently participating in the study
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
45 participants (actual)

Study arms

  • Experimental
    Random Nicotine Delivery

    One 0 mg or 4 mg nicotine film every 3-4 hours for a total of four films per day (not to exceed three non-consecutive 4 mg films in one day) for 6 weeks.

    Drug: Nicotine Film

  • Active comparator
    Steady State Nicotine Delivery

    One 2 mg nicotine film every 3-4 hours for a total of four films per day for 6 weeks.

    Drug: Nicotine Film

  • Placebo comparator
    Placebo Control

    One 0 mg nicotine film every 3-4 hours for a total of four films per day for 6 weeks.

    Drug: Nicotine Film

Interventions

  • DrugNicotine Film

    Three doses of nicotine films will be used in this project: 0 mg, 2 mg, and 4 mg. The active pharmaceutical ingredient in the nicotine film product is nicotine polacrilex (20%, USP). The film has a muco-adhesive property and allows nicotine to be absorbed through the oral mucosa. After placement in the oral cavity, the nicotine film dissolves in less than five minutes. The film is in the form of 1 inch x 1 inch square and weighs about 100 mg. Nicotine films are not available in the United States in a non-investigational setting.

06

What researchers measure

Primary outcomes

  1. Change in Number of Cigarettes Smoked Per Day (CPD)

    CPD is measured with the use of daily cigarette logs which are completed daily by participants and returned to the study center at each visit. The CPD measure will be the average of the past 7 days.

    Time frame: Baseline and 4 weeks after Target Quit Date

  2. Change in Exhaled Carbon Monoxide (CO) Measurement

    Mean change in exhaled CO (parts per million \[ppm\])

    Time frame: Baseline and 4 weeks after Target Quit Date

Secondary outcomes

  1. Change in Questionnaire of Smoking Urges-Brief (QSU-Brief) Total Score

    The QSU-Brief, with a possible total score range of 10 to 70, is an instrument used to measure cigarette craving. A score of 10 on this scale indicates very low cigarette craving, while a score of 70 indicates very high cigarette craving.

    Time frame: Baseline and 4 weeks after Target Quit Date

  2. Change in Fagerstrom Test for Nicotine Dependence (FTND) Total Score

    Nicotine dependence will be assessed via the FTND, a measure with total scores ranging from 0 (very low dependence) to 10 (very high dependence).

    Time frame: Baseline and 4 weeks after Target Quit Date

  3. Subjective Ratings Scale for Nicotine Film Use

    The scale is comprised of 21 items. Each item is rated on a scale 1-7, where 1 is equal to not at all and 7 is equal to extremely. The total score is the average score of all 21 items. The total score ranges from 1-7.

    Time frame: 4 weeks after Target Quit Date

  4. Side Effects From Nicotine Film Use

    Total score ranges from 0 - 36 with lower scores indicating lesser side effects.

    Time frame: 4 weeks after Target Quit Date

07

Results

Posted Jan 22, 2021

Participant flow

Participant flow — Overall Study
MilestoneRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Started151515
Completed12812
Not completed373

Outcome measures

PrimaryChange in Number of Cigarettes Smoked Per Day (CPD)

CPD is measured with the use of daily cigarette logs which are completed daily by participants and returned to the study center at each visit. The CPD measure will be the average of the past 7 days.

Time frame:
Baseline and 4 weeks after Target Quit Date
Reported as:
Mean · cigarettes per day
Change in Number of Cigarettes Smoked Per Day (CPD)
cigarettes per dayRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Change in Number of Cigarettes Smoked Per Day (CPD)-10.3 ± 6.1-9.0 ± 8.0-7.6 ± 5.3
Statistical analysis
  • Random Nicotine Delivery vs Steady State Nicotine Delivery vs Placebo Control · ANOVA · p = .55
PrimaryChange in Exhaled Carbon Monoxide (CO) Measurement

Mean change in exhaled CO (parts per million \[ppm\])

Time frame:
Baseline and 4 weeks after Target Quit Date
Reported as:
Mean · parts per million
Change in Exhaled Carbon Monoxide (CO) Measurement
parts per millionRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Change in Exhaled Carbon Monoxide (CO) Measurement-16 ± 18.6-5.9 ± 13.4-10.5 ± 9.1
Statistical analysis
  • Random Nicotine Delivery vs Steady State Nicotine Delivery vs Placebo Control · ANOVA · p = .2146
SecondaryChange in Questionnaire of Smoking Urges-Brief (QSU-Brief) Total Score

The QSU-Brief, with a possible total score range of 10 to 70, is an instrument used to measure cigarette craving. A score of 10 on this scale indicates very low cigarette craving, while a score of 70 indicates very high cigarette craving.

Time frame:
Baseline and 4 weeks after Target Quit Date
Reported as:
Mean · QSU Total Score
Change in Questionnaire of Smoking Urges-Brief (QSU-Brief) Total Score
QSU Total ScoreRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Change in Questionnaire of Smoking Urges-Brief (QSU-Brief) Total Score-.55 ± 1.46-.55 ± 1.36-.11 ± .97
Statistical analysis
  • Random Nicotine Delivery vs Steady State Nicotine Delivery vs Placebo Control · ANOVA · p = .5642
SecondaryChange in Fagerstrom Test for Nicotine Dependence (FTND) Total Score

Nicotine dependence will be assessed via the FTND, a measure with total scores ranging from 0 (very low dependence) to 10 (very high dependence).

Time frame:
Baseline and 4 weeks after Target Quit Date
Reported as:
Mean · FTND Total Score
Change in Fagerstrom Test for Nicotine Dependence (FTND) Total Score
FTND Total ScoreRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Change in Fagerstrom Test for Nicotine Dependence (FTND) Total Score-1.1 ± 1.44-.53 ± .92-.53 ± 1.46
Statistical analysis
  • Random Nicotine Delivery vs Steady State Nicotine Delivery vs Placebo Control · ANOVA · p = .4353
SecondarySubjective Ratings Scale for Nicotine Film Use

The scale is comprised of 21 items. Each item is rated on a scale 1-7, where 1 is equal to not at all and 7 is equal to extremely. The total score is the average score of all 21 items. The total score ranges from 1-7.

Time frame:
4 weeks after Target Quit Date
Reported as:
Mean · score on a scale
Subjective Ratings Scale for Nicotine Film Use
score on a scaleRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Subjective Ratings Scale for Nicotine Film Use3.32 ± .712.82 ± .462.74 ± .57
Statistical analysis
  • Random Nicotine Delivery vs Steady State Nicotine Delivery vs Placebo Control · ANOVA · p = .0348
SecondarySide Effects From Nicotine Film Use

Total score ranges from 0 - 36 with lower scores indicating lesser side effects.

Time frame:
4 weeks after Target Quit Date
Reported as:
Mean · score on a scale
Side Effects From Nicotine Film Use
score on a scaleRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
Side Effects From Nicotine Film Use17.77 ± 4.3215.36 ± 3.3217.13 ± 5.15
Statistical analysis
  • Random Nicotine Delivery vs Steady State Nicotine Delivery vs Placebo Control · ANOVA · p = .4040

Adverse events

Collected over Adverse event data was collected at each follow-up visit over a period of 7 weeks total.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Random Nicotine Delivery0/15 (0%)0/15 (0%)9/15 (60%)
Steady State Nicotine Delivery0/15 (0%)0/15 (0%)11/15 (73.3%)
Placebo Control0/15 (0%)0/15 (0%)8/15 (53.3%)
Most frequent other events
Most frequent other events
EventRandom Nicotine DeliverySteady State Nicotine DeliveryPlacebo Control
HiccupsGastrointestinal disorders2/155/150/15
DyspepsiaGastrointestinal disorders4/152/151/15
NauseaGastrointestinal disorders2/150/154/15
OtherInvestigations0/153/153/15
VomittingGastrointestinal disorders2/150/150/15
AnxietyPsychiatric disorders1/151/150/15

Baseline characteristics

Age, Continuous
Age, Continuous(years)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
Mean42.2 ± 9.244.0 ± 8.143.2 ± 5.843.1 ± 7.7
Sex: Female, Male
Sex: Female, Male(Participants)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
Female10131134
Male52411
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
Hispanic or Latino0101
Not Hispanic or Latino15141544
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
American Indian or Alaska Native0000
Asian0011
Native Hawaiian or Other Pacific Islander0000
Black or African American1012
White14151342
More than one race0000
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
United States15151545
Cigarettes Per Day
Cigarettes Per Day(Cigarettes per day)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
Mean19.6 ± 7.718.8 ± 6.616.8 ± 4.518.4 ± 6.4
Fagerstrom Test for Nicotine Dependence Total Score
Fagerstrom Test for Nicotine Dependence Total Score(Scores on a scale)Random Nicotine DeliverySteady State Nicotine DeliveryPlacebo ControlTotal
Mean5.0 ± 1.44.9 ± 1.14.3 ± 1.84.7 ± 1.5
08

Study locations

1 site
  • Penn State Health Milton S. Hershey Medical Center
    Hershey, Pennsylvania 17033, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · May 13, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Mar 2019 to primary completion in Nov 2019, 8 months.

Results were first posted in Jan 2021, 1 year 1 month after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 14, 2018
First posted
Sep 18, 2018
StartActual
Mar 12, 2019
Primary completionActual
Nov 25, 2019
CompletionActual
Nov 25, 2019
Results first posted
Jan 22, 2021
Last update
Jan 22, 2021
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jan 22, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03674970
Lead sponsor
Milton S. Hershey Medical Center
Collaborators
National Institute on Drug Abuse (NIDA)
Responsible party
Patricia Sue Grigson (Director, Penn State Addiction Center for Translation and Professor of Neural and Behavioral Sciences, Milton S. Hershey Medical Center) — Principal investigator
First posted
Sep 18, 2018
Start date
Mar 12, 2019
Primary completion
Nov 25, 2019
Completion
Nov 25, 2019
Results posted
Jan 22, 2021
Last update
Jan 22, 2021

Study contacts

Patricia S Grigson, PhD
principal investigator · Penn State College of Medicine
Jonathan Foulds, PhD
principal investigator · Penn State College of Medicine
Christopher Sciamanna, MD
study director · Penn State College of Medicine

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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