Personalized Dosing of Nicotine Replacement (NRT to Effect)

Personalized Dosing of Nicotine Replacement for Smoking Cessation: An Effectiveness Randomized Placebo-controlled Trial

Medications for smoking cessation are currently only effective in helping a minority of smokers quit. Drug development is slow and expensive, so there is much interest in optimizing the effectiveness of existing treatments and medications. Current standard doses of nicotine replacement therapy (NRT) are not effective for many smokers and in many cases provide less nicotine compared to when a smoker is smoking their usual number of cigarettes. The proposed study will test if a personalized dose of nicotine patch (up to 84mg) will improve quitting success in those who do not respond to a standard dose of NRT (21mg).

Study Overview

• Status: Completed
• Conditions: Tobacco Use Disorder; Nicotine Dependence
• Intervention / Treatment: Drug: Nicotine Patch; Drug: Placebos

Detailed Description

A total of 500 smokers will be enrolled from two smoking cessation clinics to participate in this study. After 2 weeks of usual treatment with 21mg patch, participants who fail to quit smoking will be randomized to receive either escalating doses of active nicotine patches, or placebo patches, for 10 weeks. Those who stop smoking during the first 2 weeks of usual treatment will continue with 21mg patch treatment for 10 weeks as an additional comparison group. In addition to the medication, participants in all groups will receive brief behavioral counselling. Subjects will return to the clinic at weeks 26 and 52 to assess whether or not they are still abstinent from smoking and self-reports of non-smoking will be confirmed using a urine test for nicotine by-product (cotinine) levels. Exhaled carbon monoxide (CO) will be recorded as an additional measure. Study follow-up visits can be conducted virtually if needed.

The goal of the proposed study is to optimize the current gold standard smoking cessation treatment (nicotine patch plus brief counseling) in order to further increase quit rates. Evidence supporting the effectiveness of personalized doses of NRT could change current practice in a wide variety of healthcare settings. Given the strong link between smoking and cancer, and evidence that quitting smoking at any age diminishes this risk, even small increases in absolute quit rates can have a substantial population-level impact on reducing the incidence of smoking-related cancers, reducing mortality rates and associated healthcare costs.

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
    • Toronto, Ontario, Canada, M6J 1H4
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Daily tobacco smoker of ≥10 cigarettes per day
2. Aged 18 to 75 years old
3. Interested in using tNRT as the only smoking cessation aid
4. Intending to quit smoking within the next 30 days

Exclusion Criteria:

1. At least weekly use of tobacco products other than cigarettes and not willing to stop for the duration of the study
2. Breast feeding, pregnancy or not using a reliable form of birth control
3. Any generalized skin disorders precluding the use of the patch
4. Any life threatening arrhythmias or severe/worsening angina pectoris or within two weeks of experiencing a myocardial infarction or cerebral vascular accident
5. Currently using or has used NRT or other smoking cessation pharmacotherapy within the past two weeks
6. Any known hypersensitivity or allergies to any of the components comprising the nicotine patch
7. Current active substance dependence (excluding caffeine) which would compromise study compliance
8. Current unstable psychiatric condition which would compromise study compliance
9. Diagnosis of terminal illness
10. Current regular use of e-cigarettes or other vaping devices containing nicotine and not willing to stop for the duration of 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: Experimental Condition; Participants unable to quit smoking after 2 weeks of treatment with 21mg nicotine patch will get 21mg nicotine patches plus additional active nicotine patches until achieving 7 consecutive days of abstinence over the next 5 weeks; maximum daily patch dose, 84mg/day	Drug: Nicotine Patch; Active nicotine patch of 21 mg, 14 mg and 7 mg; Other Names: Nicoderm
Placebo Comparator: Placebo Condition; Participant unable to quit smoking after 2 weeks of treatment with 21mg nicotine patch will get 21mg nicotine patches plus placebo patches until 7 consecutive days of abstinence over the next 5 weeks; Maximum daily patch dose, 21mg active nicotine patch plus 3 placebo 21mg patches.	Drug: Nicotine Patch; Active nicotine patch of 21 mg, 14 mg and 7 mg; Other Names: Nicoderm; Drug: Placebos; Matching placebo patches of 21 mg, 14 mg and 7 mg; Other Names: Placebo patch
Active Comparator: Quit condition; Participants able to quit for 7 consecutive days during the first 2 weeks of treatment with 21mg nicotine patch will continue open label 21mg active nicotine patches for the remaining 10 weeks.	Drug: Nicotine Patch; Active nicotine patch of 21 mg, 14 mg and 7 mg; Other Names: Nicoderm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Short term continuous abstinence	YES, If self-reported 4 weeks of abstinence without a single puff of a cigarette or any other tobacco product. Else, NO.	weeks 9 to 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term continuous abstinence	YES, if self-reported abstinence without a single puff of cigarette and urine cotinine less than 200ng/ml. Else, NO.	weeks 9-26
Long term continuous abstinence	YES, if, self-reported abstinence without a single puff of cigarette and urine cotinine less than 200ng/ml. Else, NO.	weeks 9-52

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health
• Collaborators: Ottawa Heart Institute Research Corporation; Canadian Cancer Society (CCS)
• Investigators: Principal Investigator: Peter Selby, MBBS, Centre for Addiction and Mental Health; Principal Investigator: Laurie Zawertailo, PhD, Centre for Addiction and Mental Health

Publications and helpful links

General Publications

• Zawertailo L, Hendershot CS, Tyndale RF, Le Foll B, Samokhvalov AV, Thorpe KE, Pipe A, Reid RD, Selby P. Personalized dosing of nicotine replacement therapy versus standard dosing for the treatment of individuals with tobacco dependence: study protocol for a randomized placebo-controlled trial. Trials. 2020 Jun 29;21(1):592. doi: 10.1186/s13063-020-04532-7.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2018
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): December 11, 2023

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: December 21, 2016
• First Posted (Estimated): December 22, 2016

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Smoking Cessation; Abstinence; Placebo; Randomized Clinical Trial; Nicotine Patch; Nicotine Replacement Therapy; Double blind
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; 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: 039/2015

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