Clinical trials

A review of the sports medicine literature reveals a clear underrepresentation of female athletes in research. In the current era of precision medicine, increasing attention has been directed toward the regulatory roles of estrogen and progesterone in athletic performance and health optimization. Regular fluctuations in estrogen and progesterone across menstrual cycle phases (i.e., early follicular, late follicular, and mid-luteal phases) may influence strength performance, hydration status, body composition, and energy balance. However, few studies have examined these outcomes using hormonal confirmation of menstrual cycle phases. Monophasic oral contraceptive use also represents a highly relevant hormonal condition among female athletes, as exogenous hormones suppress endogenous ovarian fluctuations and create distinct hormonal profiles across active pill-consumption and withdrawal phases. Nevertheless, the influence of oral contraceptive phases on strength-related outcomes, hydration markers, body water regulation, body composition, and energy balance remains insufficiently characterized, particularly in comparison with naturally menstruating athletes. In response to these gaps, this longitudinal observational study primarily aims to examine variations in strength-related outcomes across three distinct menstrual cycle phases (early follicular, late follicular, and mid-luteal) in eumenorrheic athletes. Secondary objectives include: (i) conducting within- and between-group comparisons of hydration status, energy balance, and strength outcomes (maximal, endurance, and explosive torque) in naturally menstruating athletes and oral contraceptive users; (ii) testing the reliability of methods used to assess body water, energy expenditure, and body composition across the menstrual cycle; (iii) exploring associations between energy availability, resting energy expenditure, and sex hormone concentrations across menstrual cycle phases; and (iv) testing, validating, and proposing methodological recommendations for the use of bioelectrical impedance analysis in tracking fluid-related changes across hormonal phases. To achieve these goals, the study will use a longitudinal observational design involving 40 female athletes, including 24 naturally menstruating athletes and 16 oral contraceptive users. Naturally menstruating athletes will be assessed during the early follicular, late follicular, and mid-luteal phases of the menstrual cycle, while oral contraceptive users will be assessed across pill-consumption and withdrawal phases. Measurements will be conducted across the three menstrual cycle phases and across oral contraceptive use phases, and will include: i) maximal voluntary isometric strength assessed using handgrip dynamometry, bench press, and leg press; ii) serum estrogen and progesterone; iii) body water and its compartments, and water turnover by dilution techniques; iv) hydration status by plasma osmolality, sodium, and vasopressin; v) energy balance by doubly labeled water and body composition changes; vi) resting energy expenditure by indirect calorimetry.

Breast cancer-related lymphedema (BCRL) is a common and debilitating condition that affects quality of life, mobility, and well-being. While exercise was once thought to worsen symptoms, current evidence suggests it may improve lymphatic function and symptom management. The LymFit project will test a 12-week combined exercise program (aerobic + resistance) in breast cancer survivors with BCRL compared to usual care. This investigation aims to unravel the effects of a combined exercise program on BCRL management. A 12-week randomized controlled trial will be conducted with two arms: a combined exercise intervention (strength + aerobic training) and a control group. The LymFit project primarily aims to assess the effects of 12 weeks of combined exercise on L-Dex in BCRL patients. Secondary objectives include evaluating exercise's effects on i) ECW:ICW ratio (dilution techniques); ii) Body composition (dual-energy X-ray absorptiometry), handgrip strength (dynamometry), cardiorespiratory fitness, quality of life, arm disability, anxiety, depression (questionnaires), and inflammatory profile (blood analysis). The project also examines acute exercise (pre- to post-session) responses on iii) Lymphedema (L-Dex) and iv) Fluid shifts (ultrasound muscle thickness + PV measurement). By integrating clinical outcomes with mechanistic evaluations, this randomized controlled trial seeks to generate evidence-based recommendations for exercise in BCRL management and improve understanding of lymphatic fluid dynamics in this population.

The "More Health, Less Diabetes" project is a hybrid randomized controlled trial to prevent type 2 diabetes in individuals at risk through structured exercise and lifestyle education. While exercise benefits for people with diabetes are well-documented, evidence remains limited on the effectiveness and cost-effectiveness of in-person and home-based exercise programs in a prediabetic population. This study aims to understand the clinical and cost-effectiveness of a three-arm RCT (online, in-person, and a control group) in people at high risk of developing T2DM. This 12-month program includes six months of supervised exercise (3 times/week) and a six-month follow-up. During the first six months, both intervention groups will attend educational sessions to improve health literacy and promote healthy habits. The primary outcome will be 2h glycemia in an oral glucose tolerance test. Secondary outcomes include other aspects of glycemic control (HbA1c, fasting glycemia, HOMA-IR, Matsuda index), 24-hour movement, body composition, vascular health, physical fitness, and cost-effectiveness using a social return on investment approach.

Coronary artery disease (CAD) is associated with autonomic dysfunction and is characterized by reduced heart rate variability (HRV) and impaired heart rate recovery. Regular exercise improves cardiovascular outcomes in CAD, with high-intensity interval training (HIIT) showing superior benefits compared to moderate-intensity continuous training (MICT). However, the full potential of exercise is not used in the clinical context since some of the training principles are neglected, contributing to a high number of exercise non-responders. HRV-guided training has been identified as an alternative prescription technique for cardiovascular endurance exercise and has contributed to greater improvements compared to standard prescriptions. Thus, this study aims to assess the chronic effects of exercise on cardiovagal modulation, baroreflex sensitivity, arterial stiffness, and cardiorespiratory fitness in patients with CAD, specifically determining whether heart rate variability-guided training yields different outcomes compared to a traditional prescription in a 12-week exercise intervention. A total of 48 participants, will be recruited and randomized into one of 3 groups: high-intensity interval training (HIIT), moderate-intensity continuous training (MICT), and HRV-guided training. The intervention will consist of 12 weeks of supervised exercise, with 3 weekly sessions. Participants in the HRV-guided training group will have their exercise intensity adjusted based on their individual HRV profiles. Moderate- or high-intensity sessions are prescribed when the 7-day rolling average of LnRMSSD remains within the smallest worthwhile change (SWC). If it falls outside the SWC, low-intensity sessions or rest are recommended. In the HIIT group, sessions will consist of 4 bouts of 2 minutes at 80-90% HRR during the first 4 weeks, increasing to 6 bouts of 2 minutes at the same intensity in weeks 5-8, and progressing to 6 bouts of 2 minutes at 90% HRR in the final 4 weeks. In the MICT group, participants will perform continuous sessions starting with 2x10 minutes at 50-60% HRR in the first 4 weeks, progressing to 2x12 minutes at the same intensity in weeks 5-8, and increasing to 2x15 minutes at 60-70% HRR in the final phase. Cardiovagal modulation, cardiorespiratory fitness, BRS, and AS will be assessed at the baseline and after the 12 weeks of intervention. Most cardiac rehabilitation programs use the "one-size-fits-all" approach, which is a limitation of the literature, leading to a large number of exercise nonresponders to changes in cardiorespiratory fitness. HRV-guided training seems to be a more individualized method of aerobic prescription and may lead to greater improvements in cardiorespiratory fitness and in cardiovagal modulation. This study will contribute to generate evidence regarding aerobic exercise prescription in cardiac rehabilitation.