MC-NRT: Smoking Cessation and Menstrual Cycle Phase: A Randomized Controlled Trial

Sponsor

Centre for Addiction and Mental Health (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05515354

Collaborator

Canadian Cancer Society (CCS) (Other)

1,200

Enrollment

Location

Arms

35.8

Anticipated Duration (Months)

33.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Tobacco use is a risk factor for at least 20 types of cancer and remains the leading preventable cause of cancer in Canada (Poirier et al., 2019; World Health Organization, 2020). Smoking cessation is an important cancer prevention strategy for the close to 2 million Canadian women who currently smoke (Statistics Canada, 2020). However, findings from controlled trials and real-world clinical settings indicate that women have greater difficulty achieving abstinence following a quit attempt than men (Piper et al., 2010; Smith et al., 2016). There is some evidence that hormonal levels and fluctuations throughout the menstrual cycle (MC) may contribute to the greater difficulty women experience when trying to quit smoking (Weinberger et al., 2015). In this study, we will test targeting the start of a quit attempt using nicotine replacement therapy (NRT) to specific phases of MC. We hypothesize that starting a quit attempt during the first half of MC (follicular phase) will result in increased quit success compared to starting during the second half of MC (luteal phase) or the usual practice of not targeting quit start date to MC phase (Carpenter et al., 2008; Franklin et al., 2008; Weinberger et al., 2015).

Condition or Disease	Intervention/Treatment	Phase
Nicotine Dependence Tobacco Smoking Smoking Cessation Nicotine Use Disorder Substance Use Disorders	Other: Timing of nicotine replacement therapy start date Drug: Nicotine Replacement Therapy Agent	Phase 4

Detailed Description

Evidence for the influence of the menstrual cycle (MC) phase on smoking cessation outcomes is contradictory and has been limited by small samples and a lack of clarity surrounding ideal quit date timing (Carpenter et al., 2008; Franklin et al., 2008; Saladin et al., 2015; Weinberger et al., 2015). Therefore, we plan to conduct a large, rigorously designed study to clarify whether targeting quit date to either the follicular or luteal phase of MC improves quit success. The primary hypothesis states that participants assigned a TQD in the follicular phase of their MC will be more likely to have quit successfully on day 7 of treatment than participants setting their own TQD (usual care). As secondary objectives, we are aiming to study quit at the end of treatment and 6 months post-TQD.

Participants will enroll in an online smoking cessation program providing nicotine replacement therapy (NRT) and behavioral support. Participants will receive a 6-week supply of NRT consisting of nicotine patch plus their choice of nicotine gum or lozenge, which they will be instructed to start on their target quit date (TQD). We will randomize eligible individuals to set a TQD: [1] during the mid-luteal phase of their MC (6-8 days pre-onset of menses), [2] during the mid-follicular phase of their MC (6-8 days post-onset of menses), or [3] within 30 days of enrollment with no regard to MC phase (usual care). Behavioural support will consist of a free downloadable app (My Change Plan) and brief videos delivered via e-mail. These videos will be produced by the CAMH Nicotine Dependence Service and will focus on health behavior change strategies such as building a quit plan, coping with cravings, and relapse prevention.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Coordinating Smoking Cessation Treatment With Menstrual Cycle Phase to Improve Quit Outcomes: A Randomized Controlled Trial

Anticipated Study Start Date :

Sep 6, 2022

Anticipated Primary Completion Date :

Aug 31, 2024

Anticipated Study Completion Date :

Aug 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mid-Follicular Phase Target Quit Date Participants will start their quit attempts during the mid-follicular phase of their MC (6-8 days post-onset of menses). Each participant will be provided with a range of appropriate dates based on the information about their menstrual cycle, and they will select a target quit date from the range. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.	Other: Timing of nicotine replacement therapy start date Nicotine replacement therapy and abstinence from smoking are initiated at a specific period with regard to the menstrual cycle. Other Names: Timing of target quit date Drug: Nicotine Replacement Therapy Agent Nicotine patch and a choice of nicotine gum or lozenge (2 mg) for 6 weeks. Participants who smoke 10 or more cigarettes per day receive a package of 21 mg, 14 mg, and 7 mg nicotine patches. For participants who smoke 5-9 (inclusive) cigarettes per day, the package contains 14 mg and 7 mg nicotine patches. Other Names: Nicotine Patch Nicotine Gum Nicotine Lozenge
Experimental: Mid-Luteal Phase Target Quit Date Participants will start their quit attempts during the mid-luteal phase of their MC (6-8 days pre-onset of menses). Each participant will be provided with a range of appropriate dates based on the information about their menstrual cycle, and they will select a target quit date from the range. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.	Other: Timing of nicotine replacement therapy start date Nicotine replacement therapy and abstinence from smoking are initiated at a specific period with regard to the menstrual cycle. Other Names: Timing of target quit date Drug: Nicotine Replacement Therapy Agent Nicotine patch and a choice of nicotine gum or lozenge (2 mg) for 6 weeks. Participants who smoke 10 or more cigarettes per day receive a package of 21 mg, 14 mg, and 7 mg nicotine patches. For participants who smoke 5-9 (inclusive) cigarettes per day, the package contains 14 mg and 7 mg nicotine patches. Other Names: Nicotine Patch Nicotine Gum Nicotine Lozenge
Active Comparator: Randomly Selected Target Quit Date (Usual Care) Participants will start their quit attempts within 30 days of their enrollment into the study. They will select their target quit dates without regard for their MC. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.	Drug: Nicotine Replacement Therapy Agent Nicotine patch and a choice of nicotine gum or lozenge (2 mg) for 6 weeks. Participants who smoke 10 or more cigarettes per day receive a package of 21 mg, 14 mg, and 7 mg nicotine patches. For participants who smoke 5-9 (inclusive) cigarettes per day, the package contains 14 mg and 7 mg nicotine patches. Other Names: Nicotine Patch Nicotine Gum Nicotine Lozenge

Arm

Intervention/Treatment

Experimental: Mid-Follicular Phase Target Quit Date

Participants will start their quit attempts during the mid-follicular phase of their MC (6-8 days post-onset of menses). Each participant will be provided with a range of appropriate dates based on the information about their menstrual cycle, and they will select a target quit date from the range. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.

Other: Timing of nicotine replacement therapy start date

Nicotine replacement therapy and abstinence from smoking are initiated at a specific period with regard to the menstrual cycle.

Other Names:

Timing of target quit date

Drug: Nicotine Replacement Therapy Agent

Nicotine patch and a choice of nicotine gum or lozenge (2 mg) for 6 weeks. Participants who smoke 10 or more cigarettes per day receive a package of 21 mg, 14 mg, and 7 mg nicotine patches. For participants who smoke 5-9 (inclusive) cigarettes per day, the package contains 14 mg and 7 mg nicotine patches.

Other Names:

Nicotine Patch

Nicotine Gum

Nicotine Lozenge

Experimental: Mid-Luteal Phase Target Quit Date

Participants will start their quit attempts during the mid-luteal phase of their MC (6-8 days pre-onset of menses). Each participant will be provided with a range of appropriate dates based on the information about their menstrual cycle, and they will select a target quit date from the range. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.

Other: Timing of nicotine replacement therapy start date

Nicotine replacement therapy and abstinence from smoking are initiated at a specific period with regard to the menstrual cycle.

Other Names:

Timing of target quit date

Drug: Nicotine Replacement Therapy Agent

Other Names:

Nicotine Patch

Nicotine Gum

Nicotine Lozenge

Active Comparator: Randomly Selected Target Quit Date (Usual Care)

Participants will start their quit attempts within 30 days of their enrollment into the study. They will select their target quit dates without regard for their MC. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.

Drug: Nicotine Replacement Therapy Agent

Other Names:

Nicotine Patch

Nicotine Gum

Nicotine Lozenge

Outcome Measures

Primary Outcome Measures

7-day point prevalence of abstinence [7 days post-target quit date]
Proportion of the sample that has been abstinent from smoking for 7 days at the time of assessment (i.e., managed to quit smoking on their target quit date).

Secondary Outcome Measures

End-of-treatment 7-day point prevalence of abstinence [6 weeks post-target quit date]
Proportion of the sample that has been abstinent from smoking for at least 7 days at the time of assessment.
Follow-up 7-day point prevalence of abstinence [6 months post-target quit date]
Proportion of the sample that has been abstinent from smoking for at least 7 days at the time of assessment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Must provide informed consent following the CAMH REDCap e-consent framework and procedures;
Stated willingness to comply with all study procedures;
Naturally cycling individuals with regular MCs (defined as length ranging 21 to 35 days over past 6 months);
Daily smoker of ≥5 cigarettes per day (CPD) over past 6 months;
Intention to quit smoking within the next 30 days and willing to make a quit attempt on their assigned TQD;
Interested in using, and able to use, nicotine patches and gum or lozenge as a smoking cessation aid;
Willing to provide a valid e-mail address to be used for study communications and to complete online questionnaires.

Exclusion Criteria:

Current use of progesterone, estrogen, testosterone, or fertility treatment;
Current use of nicotine replacement therapy or other smoking cessation medications (e.g., varenicline, bupropion);
Use of hormonal contraceptives in the past 6 months (e.g., pill, patch, hormonal intrauterine device [IUD], ring);
Pregnancy, or trying to become pregnant in the next 2-3 months;
Known hypersensitivity or allergies to any of the components of the nicotine patch;
Daily or almost daily use of cannabis in the past 6 months;
Daily or almost daily use of tobacco or nicotine products other than cigarettes (e.g., smokeless tobacco, heat-not-burn products, e-cigarettes) in the past 6 months;
Polycystic ovary syndrome diagnosis;
Unstable psychiatric condition (including substance use disorder) which would compromise study compliance;
Life threatening arrhythmias or severe/worsening angina pectoris;
Myocardial infarction or cerebral vascular accident in the past 2 weeks; or
Diagnosed with a terminal illness.