Condition category
Cancer
Date applied
30/09/2018
Date assigned
24/10/2018
Last edited
24/10/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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 or trastuzumab scheme.

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 December 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)

Trial website

Contact information

Type

Public

Primary contact

Mr Pedro Antunes

ORCID ID

http://orcid.org/0000-0002-2511-1984

Contact details

Rua Mateus Fernandes Lote 5 nº37 1C
Covilhã
6200-142
Portugal
969270946
pantunes_14@hotmail.com

Type

Public

Additional contact

Dr Ana Joaquim

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Not applicable

Study information

Scientific title

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

Acronym

Study hypothesis

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

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

Study design

Interventional randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

No participant information sheet available

Condition

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

Phase

Drug names

Primary outcome measure

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.

Secondary outcome measures

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)

Overall trial start date

01/01/2018

Overall trial end date

01/12/2022

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

80 participants

Participant 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

Recruitment start date

01/11/2018

Recruitment end date

01/08/2020

Locations

Countries of recruitment

Portugal

Trial participating centre

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

Sponsor information

Organisation

Centro Hospitalar de Vila Nova de Gaia/ Espinho

Sponsor details

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

Sponsor type

University/education

Website

http://www.chvng.pt/

Organisation

Universidade da Beira Interior

Sponsor details

Convento de Sto. António
Covilhã
6201-001
Portugal

Sponsor type

University/education

Website

http://www.ubi.pt/

Organisation

Direção Geral de Saúde

Sponsor details

Alameda D. Afonso Henriques
45
Lisboa
1049-005
Portugal

Sponsor type

Government

Website

https://www.dgs.pt/

Funders

Funder type

Not defined

Funder name

Self funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The findings will be:
1. Involved in a doctoral thesis
2. Submitted to a peer-reviewed journal for publication.
3. Presented at conferences and the whole community concerned

IPD sharing statement:
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.

Intention to publish date

01/07/2022

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes