Effects of an exercise training program on cardiac health in women with breast cancer: the Mama Move Gaia on treatment trial

ISRCTN	ISRCTN32617901
DOI	https://doi.org/10.1186/ISRCTN32617901
Protocol serial number	Not applicable
Sponsors	Centro Hospitalar de Vila Nova de Gaia, Universidade da Beira Interior, Direção Geral de Saúde
Funder	Self funded

Submission date: 30/09/2018
Registration date: 24/10/2018
Last edited: 03/03/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Due to the improvement in survival time of breast cancer survivors, the long term effects of anti-cancer (antineoplastic) treatments are becoming increasingly apparent in this group. One of the most serious and significant effects of these treatments is cardiotoxicity (damage to the heart muscle), which can lead to cardiovascular health complications. Therefore, physical exercise is widely recommended as a supporting therapy for cancer and heart rehabilitation.
This study aims to look at the effects of supervised physical exercise on cardiotoxicity and cardiac health in women with breast cancer during antineoplastic treatment. It also aims to examine the effects of physical exercise on physical functionality, quality of life, fatigue and peripheral neuropathy (weakness, numbness and pain in the hands and feet as a result of nerve damage).

Who can participate?
Adult women with breast cancer (stage IA-IIIC) undergoing a neo/adjuvant anthracycline-containing chemotherapy.

What does the study involve?
Participants will be randomly allocated to either the intervention group or the control group. The intervention group will be asked to participate in a supervised physical exercise program for two months, which will involve aerobic exercise and resistance training, with a progressive increase in volume and intensity. The control group will not receive any exercise program. Before and after the exercise program, measurements will be taken, including blood pressure, heart rate and biomarkers, along with various questionnaires. After the final set of measurements are taken, participants in the control group will then be offered the exercise program received by the intervention group. Additionally, 24 hours before the end of each treatment cycle, blood samples will be taken from all participants.

What are the possible benefits and risks of participating?
Participants may feel the benefits derived from the supervised physical exercise such as prevention of cardiac dysfunction, improvement of cardiac health, improved physical fitness, improved quality of life, and reduced fatigue, peripheral neuropathy and pain. The possible risksof participating in the study are fractures (from exercise), lymphedema (swelling in the arms and legs), hot flushes and extra fatigue.

Where is the study run from?
Centro Hospitalar Vila Nova de Gaia/Espinho (Portugal)

When is the study starting and how long is it expected to run for?
December 2018 to August 2022

Who is funding the study?
Centro Hospitalar de Vila Nova de Gaia/Espinho, Universidade da Beira Interior e Associação de Investigação de Cuidados de Suporte em Oncologia (Portugal)

Who is the main contact?
1. Mr. Pedro Antunes (pantunes_14@hotmail.com)
2. Dr. Ana Joaquim (anaisabeljoaquim@gmail.com)

Contact information

Mr Pedro Antunes
Public

Rua Mateus Fernandes Lote 5 nº37 1C
Covilhã
6200-142
Portugal

ORCID ID	0000-0002-2511-1984
Phone	969270946
Email	pantunes_14@hotmail.com

Dr Ana Joaquim
Public

Rua Rio do Vake nº560, 3ºA
Arcozelo
4410-358
Portugal

Study information

Primary study design	Interventional
Study design	Interventional randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Effects of supervised physical exercise on cardiotoxicity and cardiac health in women breast cancer survivors during anthracycline-containing chemotherapy: a randomised controlled trial
Study objectives	We anticipate that performing physical exercise during anthracycline-containing chemotherapy or trastuzumab will be associated with: 1. Attenuation of subclinical cardiotoxicity markers, such as systolic function (left ventricular ejection fraction), myocardial deformation (global longitudinal strain), and circulating cardiac biomarkers 2. Attenuation of cardiopulmonary capacity reduction 3. Control of cardiac health parameters, such as: blood pressure, resting heart, resting heart rate variability, and recovery heart rate
Ethics approval(s)	Current ethics approval information as of 11/01/2019: Ethics committee of the Centro Hospitalar de Vila Nova de Gaia/Espinho (CHVNG/E), 19/11/2018, ref: 145/2018-1 Previous ethics approval information: The present study was submitted to the ethics committee of the Centro Hospitalar de Vila Nova de Gaia/Espinho. We expect to obtain its ethical approval by the end of October.
Health condition(s) or problem(s) studied	Breast cancer
Intervention	Patients will be randomised to either the intervention or the control group using a permutated block design with random four and six block sizes. Patients in the intervention group will perform a supervised physical exercise program specifically developed for BC patients, based on the guidelines of the American College of Sports Medicine and a close cooperation between physical sports technicians and medical staff. The physical program comprises 3 weekly sessions, oriented in small groups (3-5 patients), supervised by the main author. Each session will involve an initial warm-up (5 min) followed by strength muscle and aerobic training (60 min) and ending with a cooldown phase (5 min). During the intervention period, patients allocated to the control group will receive only the usual supportive care. There will be a 3 month follow-up period.
Intervention type	Behavioural
Primary outcome measure(s)	Current primary outcome measures as of 10/01/2019: 1. Cardiotoxicity markers: 1.1. Systolic function (left ventricular ejection fraction), assessed using standard transthoracic echocardiography at the baseline, at the end of treatment and 3 months afterwards 1.2. Myocardial deformation (global longitudinal strain), assessed using standard transthoracic echocardiography at the baseline, at the end of treatment and 3 months afterwards 1.3. Circulating cardiac biomarkers (amino-terminal pro-brain natriuretic peptide), assessed using blood samples at the baseline, 24 hours before the start of each treatment cycle, at the end of treatment and 3 months afterwards 2. Cardiac health outcomes will be assessed at the baseline, at the end of treatment and 3 months afterwards: 2.1. Resting blood pressure, measured in a seated comfortable position using a cardiac monitor 2.2. Resting heart rate, measured in a seated comfortable position using a cardiac monitor 2.3. Resting heart rate variability, measured in a seated comfortable position after at least 5 minutes of rest using a Polar V800 heart rate monitor with a Polar H7 Heart Rate Sensor chest strap. Analysis will be done using Kubios v2 Heart Rate Variability software. 2.4. Heart rate recovery (measured using a cardiac monitor after 30 seconds and 60 seconds after completion of a cardiopulmonary test), defined as the difference between peak heart rate achieved in the cardiopulmonary test and the heart rate at 30 seconds and 60 seconds following this. Previous primary outcome measures: 1. Cardiotoxicity markers: 1.1. Systolic function (left ventricular ejection fraction), assessed using standard transthoracic echocardiography at the baseline, at the end of treatment and 3 months afterwards 1.2. Myocardial deformation (global longitudinal strain), assessed using standard transthoracic echocardiography at the baseline, at the end of treatment and 3 months afterwards 1.3. Circulating cardiac biomarkers (amino-terminal pro-brain natriuretic peptide), assessed using blood samples at the baseline, 24 hours before the end of each treatment cycle, at the end of treatment and 3 months afterwards 2. Cardiac health outcomes will be assessed at the baseline, at the end of treatment and 3 months afterwards: 2.1. Resting blood pressure, measured in a seated comfortable position using a cardiac monitor 2.2. Resting heart rate, measured in a seated comfortable position using a cardiac monitor 2.3. Resting heart rate variability, measured in a seated comfortable position after at least 5 minutes of rest using a Polar V800 heart rate monitor with a Polar H7 Heart Rate Sensor chest strap. Analysis will be done using Kubios v2 Heart Rate Variability software. 2.4. Heart rate recovery (measured using a cardiac monitor after 30 seconds and 60 seconds after completion of a cardiopulmonary test), defined as the difference between peak heart rate achieved in the cardiopulmonary test and the heart rate at 30 seconds and 60 seconds following this.
Key secondary outcome measure(s)	All secondary outcomes will be measured at the baseline, at the end of treatment and 3 months afterwards: 1. Functional outcomes: 1.1. Cardiopulmonary capacity (maximum oxygen consumption), evaluated using a Bruce treadmill test with an echocardiogram and continuous analysis of the O₂/CO₂ exchange 1.2. Upper limb strength (maximum voluntary handgrip strength), assessed using a handgrip dynamometer (6 trials per participant with 3 in each arm) 1.3. Lower limb functionality, assessed using the sit-stand test 2. Health-related quality of life and fatigue, assessed using the European Organization for Research and Treatment in Cancer Quality of Life C-30 (EORTC QLQ-C30) questionnaire 3. Neuropathy-related chemotherapy, assessed using The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group -Neurotoxicity (FACT/GOG-Ntx) Scale)
Completion date	31/08/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target sample size at registration	86
Total final enrolment	93
Key inclusion criteria	Current inclusion criteria as of 10/01/2019: 1. Female 2. Aged 18 years or older 3. Histological confirmation of invasive breast cancer 4. Breast cancer stage IA-IIIC 5. Scheduled to receive neoadjuvant or adjuvant anthracycline-containing chemotherapy by decision of the Multidisciplinary Group Consultation of Centro Hospitalar de Vila Nova de Gaia/Espinho 6. Able to provide informed consent 7. Acceptance of randomization to intervention group or control group 8. Baseline assessments before anthracycline-containing chemotherapy begins. Previous inclusion criteria: 1. Female 2. Aged 18 years or older 3. Histological confirmation of invasive breast cancer 4. Breast cancer stage IA-IIIC 5. Scheduled to receive neoadjuvant or adjuvant anthracycline-containing chemotherapy and/or trastuzumab by the Multidisciplinary Group Consultation of Centro Hospitalar de Vila Nova de Gaia/Espinho decision 6. Able to provide informed consent 7. Acceptance of randomization to intervention group or control group
Key exclusion criteria	Current exclusion criteria as of 10/01/2019: 1. Contraindications to maximal exercise testing 2. Decompensated diabetes mellitus 3. Severe anaemia (<8 g/dl) uncorrectable with transfusion and/or iron and/or vitamin deficiency replacement 4. Significant heart disease (myocardial infarction, congestive heart failure, cardiomyopathy) 5. Usual medication containing beta-blockers 6. Contraindication to exercise Previous exclusion criteria: 1. Heart failure class >1 of the New York Heart Association. 2. Osteoporosis (Tscore < 2.5) 3. Contraindications to maximal exercise testing 4. Usual medication containing beta-blockers 5. Severe anaemia (<8 g/dl) that cannot be corrected with transfusion and/or replacement of iron deficiency and/or vitamin deficiency
Date of first enrolment	01/11/2018
Date of final enrolment	31/01/2022

Locations

Countries of recruitment

Portugal

Study participating centre

Centro Hospitalar de Vila Nova de Gaia/Espinho

Rua Conceição Fernandes, s/n
Vila Nova de Gaia
4434-502
Portugal

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan	The data that will support the findings of this study will be available on request from the corresponding author Pedro Antunes (pantunes_14@hotmail.com). The request will be analysed by the research team and the ethics committee that ethically approved the study.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	primary outcome results	28/02/2023	03/03/2023	Yes	No
Protocol article	protocol	15/07/2019	17/07/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

03/03/2023: The following changes have been made:
1. Publication reference added.
2. Total final enrolment added.
3. The public contact has been updated.
01/08/2022: The following changes have been made:
1. The public title has been changed from "Effects of physical exercise on cardiac health in women with breast cancer" to "Effects of an exercise training program on cardiac health in women with breast cancer: the Mama Move Gaia on treatment trial".
2. The overall trial end date has been changed from 01/12/2022 to 31/08/2022 and the plain English summary updated accordingly.
3. The intention to publish date has been changed from 01/07/2022 to 28/02/2023.
30/11/2020: The recruitment end date has been changed from 30/11/2020 to 31/01/2022.
30/10/2020: Recruitment for this study is no longer paused as of 16/09/2020.
21/05/2020: Due to current public health guidance, recruitment for this study has been paused as of 09/03/2020.
17/07/2019: Publication reference added.
11/01/2019: The ethics approval date has been added.
10/01/2019: The following changes have been made:
1. The scientific title has been changed from "Effects of supervised physical exercise on cardiotoxicity and cardiac health in women breast cancer survivors during anthracycline-containing chemotherapy or trastuzumab: a randomised controlled trial" to "Effects of supervised physical exercise on cardiotoxicity and cardiac health in women breast cancer survivors during anthracycline-containing chemotherapy: a randomised controlled trial".
2. The ethics approval information has been changed.
3. The primary outcome measures have been changed.
4. The participant inclusion criteria have been changed.
5. The participant exclusion criteria have been changed.
6. The target number of participants has been changed from 80 to 86.
7. The recruitment end date has been changed from 01/08/2020 to 30/11/2020.
8. The plain English summary has been updated to reflect the changes made.