REstoring Metabolic FLEXibility Through Combined Exercise in Breast Cancer Survivors: A Randomized Controlled Trial.

N/ANot Yet RecruitingNCT07405385

University of Castilla-La Mancha44 enrolled

Overview

The REFLEX study is a randomized, controlled clinical trial designed to evaluate the impact of a 16-week supervised, combined exercise program on metabolic flexibility and cardiorespiratory fitness in breast cancer survivors. While cancer treatments have significantly improved survival rates, the disease and its therapies often cause systemic mitochondrial dysfunction and muscle loss. This leads to persistent "metabolic inflexibility"-a reduced ability to efficiently switch between burning carbohydrates and fats for energy. This inflexibility, exacerbated by sedentary behavior and cancer-related fatigue, can severely diminish a patient's functional autonomy and overall quality of life. The trial focuses on assessing whether exercise can restore this metabolic adaptability in women aged 18 to 70 with stage I-III breast cancer who are currently on hormonal treatment and completed neo/adjuvant chemotherapy within the past 6 months. The study operates on the primary hypothesis that an individualized exercise intervention will significantly improve the participants' metabolic flexibility-measured via the metabolic crossover point-and overall aerobic capacity (VO2max) when compared to a control group. Additionally, the trial will analyze secondary outcomes, including changes in cardiovascular and metabolic risk factors, muscle strength, body composition (such as bone mineral density), and patient-reported outcomes assessing quality of life, fatigue, joint pain, anxiety, and depression. A total of 44 participants will be randomly assigned to either the intervention or control group. Participants in the intervention group will complete a 16-week program consisting of two weekly supervised sessions. Each session lasts between 55 and 85 minutes and includes a tailored combination of aerobic and strength training based on the individual's baseline fitness and metabolic thresholds. Participants in the control group. will receive standard educational materials via email, featuring healthy lifestyle and exercise guidelines from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM). To evaluate the program's effectiveness, comprehensive medical and functional assessments will be conducted at baseline, immediately after the 16-week intervention, and at a 3-month follow-up. These evaluations include submaximal and maximal exercise tests on a cycle ergometer to analyze respiratory gases, detailed blood tests, body composition imaging (DXA scans), and maximum dynamic strength testing. Ultimately, the research aims to generate high-quality evidence to optimize standard exercise recommendations for breast cancer survivors and improve their long-term health and resilience.

Study Type

Interventions

ControlBEHAVIORAL

Participants assigned to the control group receive standard care typically provided to patients in this phase of recovery. Instead of a supervised exercise program, these individuals are sent educational materials via email. This material consists of a video and official documents containing basic guidelines and recommendations for a healthy lifestyle, based on standards from the World Health Organization (WHO) and the American College of Sports Medicine (ACSM) for cancer survivors. The documents provide general instructions on physical activity, reducing sedentary behavior, and maintaining overall health habits. Like the intervention group, participants in the control group undergo all clinical and functional evaluations at the start of the study, after 16 weeks, and during a 3-month follow-up.

ExerciseBEHAVIORAL

The intervention consists of a supervised, in-person, combined exercise program lasting 16 consecutive weeks, conducted at a specialized exercise unit. Participants attend two sessions per week, with at least 48 hours of recovery between sessions, and each session lasts between 55 and 85 minutes. The program follows a "combined" methodology, meaning every session integrates both resistance (strength) and aerobic training. To ensure safety and precision, sessions are led by a graduate in Physical Activity and Sport Sciences with specialized training in oncology, and participants work in small groups of 6 to 8 people. Each session is structured into four distinct parts: a 10-minute warm-up involving low-to-moderate intensity activity and joint mobility; a resistance training block; an aerobic training block; and a cool-down featuring static stretching for 30-40 seconds per muscle group. The resistance training portion utilizes a "full body" approach.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Women aged between 18 and 70 years. * Confirmed diagnosis of breast cancer in stages I to III. * Received neo-adjuvant or adjuvant chemotherapy and completed the chemotherapy treatment within the 6 months prior to study enrolment. * Residency within a distance of less than 40 km from the Hospital Universitario de Toledo. Exclusion Criteria: * Diagnosis of stage IV breast cancer. * Undergone major surgery within the 4 months prior to enrolment or scheduled for breast reconstruction surgery during the study period. * Diagnosis of diabetes mellitus with poor glycaemic control, defined as an HbA1c value greater than or equal to 8.5%. * Presence of an acute infectious disease. * Absolute or relative medical contraindications for physical exercise or maximal exercise stress testing, according to the American College of Sports Medicine (ACSM) guidelines. * Serious cardiac or cardiovascular disease, including a history of myocardial infarction, heart failure, or known cardiomyopathy. * Regular consumption of beta-blockers or any medication that alters the functioning of the nervous system. * Currently active, defined as engaging in more than 150 minutes per week of structured physical exercise during the 6 months prior to enrolment.

Outcomes

Primary Outcomes

Change in Crossover point

Assessment of the metabolic crossover point determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry) to calculate substrate oxidation rates.

Time frame: 7 months

Changes in Cardiorespiratory Fitness

Assessment of cardiorespiratory capacity determined through a maximal cardiopulmonary exercise test (stress test) on a cycle ergometer

Time frame: 7 months

Secondary Outcomes

Change in maximal fat oxidation

Assessment of the maximal fat oxidation rate determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry).

Time frame: 7 months

Change in maximal carbohydrate oxidation

Assessment of the maximal carbohydrate oxidation rate determined through an individualized, submaximal incremental exercise test on a cycle ergometer with continuous measurement of expired gases (indirect calorimetry).

Time frame: 7 months

Change in Lower Body Muscular Strength

Estimated one-repetition maximum (1RM) for the leg press. Measurements will be obtained through force-velocity profiling using a linear position transducer.

Time frame: 7 months

Change in Upper-Body Muscular Strength

Estimated one-repetition maximum (1RM) for the vertical press. Measurements will be obtained through force-velocity profiling using a linear position transducer.

Time frame: 7 months

Change in 6-Minute Walk Test

Evaluation of physical performance using the 6-minute walk test.

Time frame: 7 months

Change in Lower-Body Muscular Endurance (30-sec CST)

Evaluation of physical performance using the 30-second chair stand test.

Time frame: 7 months

Change in Grip Strength

Evaluation of upper-body isometric strength using a handheld dynamometer.

Time frame: 7 months

Change in Body Mass Index (BMI)

BMI will be calculated as weight in kilograms divided by height in meters squared (kg/m2).

Time frame: 7 months

Change in Body Fat Percentage

Assessment of total body fat percentage using Dual-Energy X-ray Absorptiometry (DXA) scan.

Time frame: 7 months

Change in Lean Mass Percentage

Assessment of total lean muscle mass percentage using Dual-Energy X-ray Absorptiometry (DXA) scan.

Time frame: 7 months

Change in Bone Mineral Density

Assessment of bone mineral density (g/cm²) determined through a Dual-Energy X-ray Absorptiometry (DXA) scan.

Time frame: 7 months

Change in EQ-5D-5L Visual Analogue Scale (VAS)

Evaluation of self-rated health using the EuroQol Visual Analogue Scale (EQ VAS). The scale is a vertical line with minimum value 0 (worst imaginable health) and maximum value 100 (best imaginable health). Higher scores indicate a better perceived health outcome.

Time frame: 7 months

Change in EQ-5D-5L Index Score

Evaluation of health-related quality of life based on the EuroQol 5-dimension 5-level (EQ-5D-5L) descriptive system. This system assesses five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Responses are converted into a single index score using a valuation algorithm. The index scale typically ranges from less than 0 to 1, where higher scores indicate a better outcome.

Time frame: 7 months

Change from Baseline in Cancer-Related Fatigue (FACIT-F)

Evaluation using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Total scores range from 0 to 52, where higher scores indicate lower levels of fatigue.

Time frame: 7 months

Change in Hospital Anxiety and Depression Scale (HADS)

Evaluation using the Hospital Anxiety and Depression Scale (HADS). The total score ranges from 0 to 42, where higher scores indicate greater psychological distress.

Time frame: 7 months

REstoring Metabolic FLEXibility Through Combined Exercise in Breast Cancer Survivors: A Randomized Controlled Trial.

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts