Smoking Cessation and Menstrual Cycle Phase

NCT ID: NCT05515354

Last Updated: 2023-02-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 1200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-30
• Study Completion Date: 2025-08-31

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. Smoking cessation is an important cancer prevention strategy for the close to 2 million Canadian women who currently smoke. However, findings from controlled trials and real-world clinical settings indicate that women have greater difficulty achieving abstinence following a quit attempt than men. 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. In this study, the start of a quit attempt using nicotine replacement therapy (NRT) will be targeted to specific phases of MC. It was hypothesized 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.

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. Therefore, this large rigorously designed study aims 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). Quit rates at the end of treatment and 6 months post-TQD were identified as secondary objectives.

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 the participants will be instructed to start on their target quit date (TQD). Eligible individuals will be randomized to 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.

Conditions

Nicotine Dependence; Tobacco Smoking; Smoking Cessation; Nicotine Use Disorder; Substance Use Disorders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Timing of nicotine replacement therapy start date

Intervention Type: OTHER

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

Nicotine Replacement Therapy Agent

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Timing of nicotine replacement therapy start date

Intervention Type: OTHER

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

Nicotine Replacement Therapy Agent

Intervention Type: DRUG

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.

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.

Group Type: ACTIVE_COMPARATOR

Nicotine Replacement Therapy Agent

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: OTHER

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.

Intervention Type: DRUG

Other Intervention Names

Timing of target quit date; Nicotine Patch; Nicotine Gum; Nicotine Lozenge

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Canadian Cancer Society (CCS)

OTHER

Sponsor Role: collaborator

Centre for Addiction and Mental Health

OTHER

Sponsor Role: lead

Responsible Party

Laurie Zawertailo

Senior Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Laurie A Zawertailo, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre for Addiction and Mental Health

Locations

Centre for Addiction and Mental Health, Nicotine Dependence Clinic

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Laurie A Zawertailo, PhD

Role: CONTACT

laurie.zawertailo@camh.ca

4165358501 ext. 77422

Tina Kabir, BMSc

Role: CONTACT

tina.kabir@camh.ca

4165358501 ext. 37285

Facility Contacts

Laurie Zawertailo

Role: primary

laurie.zawertailo@camh.ca

416-535-8501 ext. 77422

References

Carpenter MJ, Saladin ME, Leinbach AS, Larowe SD, Upadhyaya HP. Menstrual phase effects on smoking cessation: a pilot feasibility study. J Womens Health (Larchmt). 2008 Mar;17(2):293-301. doi: 10.1089/jwh.2007.0415.

Reference Type: BACKGROUND

PMID: 18321181 (View on PubMed)

Franklin TR, Ehrman R, Lynch KG, Harper D, Sciortino N, O'Brien CP, Childress AR. Menstrual cycle phase at quit date predicts smoking status in an NRT treatment trial: a retrospective analysis. J Womens Health (Larchmt). 2008 Mar;17(2):287-92. doi: 10.1089/jwh.2007.0423.

Reference Type: BACKGROUND

PMID: 18321180 (View on PubMed)

Piper ME, Cook JW, Schlam TR, Jorenby DE, Smith SS, Bolt DM, Loh WY. Gender, race, and education differences in abstinence rates among participants in two randomized smoking cessation trials. Nicotine Tob Res. 2010 Jun;12(6):647-57. doi: 10.1093/ntr/ntq067. Epub 2010 May 3.

Reference Type: BACKGROUND

PMID: 20439385 (View on PubMed)

Poirier AE, Ruan Y, Grevers X, Walter SD, Villeneuve PJ, Friedenreich CM, Brenner DR; ComPARe Study Team. Estimates of the current and future burden of cancer attributable to active and passive tobacco smoking in Canada. Prev Med. 2019 May;122:9-19. doi: 10.1016/j.ypmed.2019.03.015.

Reference Type: BACKGROUND

PMID: 31078177 (View on PubMed)

Saladin ME, McClure EA, Baker NL, Carpenter MJ, Ramakrishnan V, Hartwell KJ, Gray KM. Increasing progesterone levels are associated with smoking abstinence among free-cycling women smokers who receive brief pharmacotherapy. Nicotine Tob Res. 2015 Apr;17(4):398-406. doi: 10.1093/ntr/ntu262.

Reference Type: BACKGROUND

PMID: 25762749 (View on PubMed)

Smith PH, Bessette AJ, Weinberger AH, Sheffer CE, McKee SA. Sex/gender differences in smoking cessation: A review. Prev Med. 2016 Nov;92:135-140. doi: 10.1016/j.ypmed.2016.07.013. Epub 2016 Jul 26.

Reference Type: BACKGROUND

PMID: 27471021 (View on PubMed)

Statistics Canada. (2020). Smokers, by age group. Retrieved August 23, 2021, from https://www150.statcan.gc.ca/t1/tbl1/en/tv.action?pid=1310009610&pickMembers%5B0%5D=1.1&pickMembers%5B1%5D=3.3&cubeTimeFrame.startYear=2018&cubeTimeFrame.endYear=2019&referencePeriods=20180101%2C20190101

Reference Type: BACKGROUND

World Health Organization. (2020). Who report on cancer: Setting priorities, investing wisely and providing care for all. World Health Organization. Retrieved August 12, 2022, from https://www.who.int/publications-detail-redirect/9789240001299

Reference Type: BACKGROUND

Weinberger AH, Smith PH, Allen SS, Cosgrove KP, Saladin ME, Gray KM, Mazure CM, Wetherington CL, McKee SA. Systematic and meta-analytic review of research examining the impact of menstrual cycle phase and ovarian hormones on smoking and cessation. Nicotine Tob Res. 2015 Apr;17(4):407-21. doi: 10.1093/ntr/ntu249.

Reference Type: BACKGROUND

PMID: 25762750 (View on PubMed)

Zawertailo L, Kabir T, Voci S, Tanzini E, Attwells S, Malat L, Veldhuizen S, Minian N, Dragonetti R, Melamed OC, Mei-Dan E, Selby P. Coordinating smoking cessation treatment with menstrual cycle phase to improve quit outcomes (MC-NRT): study protocol for a randomized controlled trial. Trials. 2023 Apr 1;24(1):251. doi: 10.1186/s13063-023-07196-1.

Reference Type: DERIVED

PMID: 37005655 (View on PubMed)

Other Identifiers

022-2022

Identifier Type: -

Identifier Source: org_study_id