Effects of Random Nicotine Delivery on Smoking Cessation

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Cigarette Smoking; Smoking (Tobacco) Addiction
• Intervention / Treatment: Drug: Nicotine Film

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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; 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.
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; 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.
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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 4 weeks after Target Quit Date
Change in Exhaled Carbon Monoxide (CO) Measurement	Mean change in exhaled CO (parts per million [ppm])	Baseline and 4 weeks after Target Quit Date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline and 4 weeks after Target Quit Date
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).	Baseline and 4 weeks after Target Quit Date
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.	4 weeks after Target Quit Date
Side Effects From Nicotine Film Use	Total score ranges from 0 - 36 with lower scores indicating lesser side effects.	4 weeks after Target Quit Date

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Jonathan Foulds, PhD, Penn State College of Medicine; Principal Investigator: Patricia S Grigson, PhD, Penn State College of Medicine; Study Director: Christopher Sciamanna, MD, Penn State College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): November 25, 2019
• Study Completion (Actual): November 25, 2019

Study Registration Dates

• First Submitted: September 14, 2018
• First Submitted That Met QC Criteria: September 14, 2018
• First Posted (Actual): September 18, 2018

Study Record Updates

• Last Update Posted (Actual): January 22, 2021
• Last Update Submitted That Met QC Criteria: January 3, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: smoking cessation; nicotine film; nicotine delivery; random nicotine delivery
• Additional Relevant MeSH Terms: Compulsive Behavior; Impulsive Behavior; Behavior, Addictive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 9977; R21DA038775 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No