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

NCT07405385 | Not Yet Recruiting

• 1 other identifier: 2024-UNIVERS-12844
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cancer; Breast Cancer; Neoplasm; Metabolic Flexibility

Outcome Measures

Primary Outcomes (2)

• 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.

  7 months

• Changes in Cardiorespiratory Fitness

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

  7 months

Secondary Outcomes (15)

• Change in maximal fat oxidation

  7 months

• Change in maximal carbohydrate oxidation

  7 months

• Change in Lower Body Muscular Strength

  7 months

• Change in Upper-Body Muscular Strength

  7 months

• Change in 6-Minute Walk Test

  7 months

Study Arms (2)

EXERCISE GROUP

EXPERIMENTAL

Behavioral: Exercise

CONTROL GROUP

OTHER

Behavioral: Control

Interventions

Control BEHAVIORAL

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.

CONTROL GROUP

Exercise BEHAVIORAL

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.

EXERCISE GROUP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Castilla-La Mancha: lead

Study Sites (1)

University of Castilla-La Mancha (PAFS Research Group)

Toledo, Toledo, 45071, Spain

Location

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms

Interventions

Exercise

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Central Study Contacts

Susana Aznar Laín

CONTACT

+34 669356600; susana.aznar@uclm.es

Alejandro Jiménez Marín

CONTACT

+34 685414255; alejandro.jimenez@uclm.es

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor

Study Record Dates

• First Submitted: January 27, 2026
• First Posted: February 12, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 28, 2026

Record last verified: 2026-01

Locations

ES (1)