Clinical trial NCT05515354: Smoking Cessation and Menstrual Cycle Phase
Official title: Coordinating Smoking Cessation Treatment With Menstrual Cycle Phase to Improve Quit Outcomes: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Nicotine Dependence
Tobacco Smoking
Smoking Cessation
Nicotine Use Disorder
Substance Use Disorders
Keywords: Menstrual Cycle
Ovarian Hormones
Smoking Cessation Treatment
Nicotine Replacement Therapy
Cancer Prevention
Randomized Controlled Trial
Estrogen
Progesterone
Lead sponsor: Centre for Addiction and Mental Health
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Society (CCS)
First posted: 2022-08-25
Enrollment: 1200
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 7-day point prevalence of abstinence
timeFrame: 7 days post-target quit date
Secondary outcomes:
measure: End-of-treatment 7-day point prevalence of abstinence
timeFrame: 6 weeks post-target quit date
measure: Follow-up 7-day point prevalence of abstinence
timeFrame: 6 months post-target quit date
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Centre for Addiction and Mental Health, Nicotine Dependence Clinic
state: Ontario
Study officials:
affiliation: Centre for Addiction and Mental Health
name: Laurie A Zawertailo, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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citation: 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.
citation: 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
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citation: 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.