Exercise to Improve Neurovascular Function in Breast Cancer Survivors

NCT06925529 | Not Yet Recruiting

• 2 other identifiers: P11723114949
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Study Rationale: Breast cancer survivors are more likely to develop cardiovascular disease (CVD) or neurocognitive disease than age-matched counterparts without a history of cancer diagnosis. Some anti-cancer treatments cause damage to the cells of heart and the walls of blood vessels, which may exacerbate neurovascular dysfunction and cancer-related cognitive impairment (symptoms such as 'chemo-brain'), as well as accelerating the onset of neurocognitive disease. Therefore, effective policies and therapeutic strategies are needed to minimize neurovascular dysfunction and neurocognitive disease in at-risk populations like breast cancer survivors. Regular exercise training is effective in slowing or preventing the development of CVD. Furthermore, higher fitness levels are associated with lower dementia risk in older adults, which may be due to better neurovascular function. However, whether exercise training incorporated into a Cardio-Oncology Rehabilitation and Exercise (CORE) programme can improve neurovascular function in breast cancer survivors is currently unknown. Therefore, the primary aim of this study will be to determine the effect of a CORE programme on neurovascular function in long-term breast cancer survivors. Study Description: This study will be a randomised controlled trial to investigate the effect of a CORE programme on neurovascular function in long-term breast cancer survivors. Participants will complete a series of baseline assessments, including lifestyle questionnaires, a cognitive function assessment, dual-energy x-ray absorptiometry (DXA), a cardiopulmonary exercise test (CPET), ultrasound assessments of arterial stiffness and vascular function, and brain magnetic resonance imaging (MRI). Furthermore, participants will wear a blood pressure monitor at home for 24 hours, and a physical activity monitor for seven days. Following completion of baseline assessments, participants will be randomised to either the CORE program or a 'usual care' group. The CORE program will include a 6-month exercise training program supervised by an Exercise Physiologist at the Baker Heart and Diabetes Institute. The usual care group will carry on with healthcare from their usual healthcare provider(s) for 6 months. Participants will then complete two follow-up study visits following completion of the 6-month intervention period, with identical procedures to the baseline study visits. Study Duration: This study involves two baseline study visits in month 1, followed by two study visits in month 7. Participants randomised to the CORE program will be asked to attend the Baker Heart and Diabetes Institute on a weekly basis for supervised exercise training sessions. However, the supervised exercise training sessions will be provided by a mix of in-person, video-conferencing and tele-health modes depending on each participants availability and needs.

Conditions

Breast Cancer Survivorship

Keywords

Breast Cancer; Survivorship; Neurovascular Function; Cerebral Blood Flow; Cardio-Oncology; Exercise Training; Neurocognitive Function

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Neurovascular Function Measured via MRI-Derived Total Cerebral Blood Flow at 6 Months

  The change in neurovascular function will be measured via total cerebral blood flow during brain magnetic resonance imaging (MRI), from pre- to post-study intervention period. Total cerebral blood flow will be measured relative to brain volume via arterial spin labeling and magnetization prepared rapid gradient echo imaging MRI scan sequences. Total cerebral blood flow will be measured in millilitres of blood per 100g of brain tissue per minute (ml.100g.min).

  6 months

Secondary Outcomes (1)

• Change from Baseline in Neurocognitive Function Measured via the Montreal Cognitive Assessment at 6 Months

  6 months

Other Outcomes (1)

• Determing if Changes from Baseline in Cardiorespiratory Fitness measured during Cardiopulomary Exercise Testing Mediate Improvements in Neurocognitive Function Measured via a Montreal Cognitive Assessment at 6 Months

  6 months

Study Arms (2)

Usual Care

NO INTERVENTION

Participants randomised to the usual care group will be provided with their usual care by their usual healthcare professional(s). The usual care group will not be prescribed any exercise training through the study. However, they will be informed that they should aim to achieve the physical activity and exercise guidelines for Australian adults or older adults depending on their age (Care, 2024). The usual care group will not be monitored throughout the study intervention period, except for the reporting of adverse events where necessary.

Cardio-Oncology Rehabilitation and Exercise Programme

EXPERIMENTAL

Participants randomised to the CORE programme will receive exercise training that is analogous to cardiac rehabilitation, but Exercise Physiologists will individualise each training program using the participants baseline CPET results to maximise adherence and improve the effectiveness of the training program beyond typical cardiac rehabilitation programs. An Exercise Physiologist will supervise two training sessions a week and monitor adherence to one other independent session at home each week for the first 12 weeks of the training program whilst exercise frequency, intensity, and time is progressively increased. Supervision of the exercise training will then be stepped down gradually after 12 weeks to a fortnightly check-in to encourage intervention adherence. Patients will be provided with a training calendar and objective tools for tracking physical activity (e.g. heart rate monitor and diary). Adherence will be monitored in real-time using a research web-based platform.

Behavioral: Cardio-Oncology Rehabilitation and Exercise Programme

Interventions

Cardio-Oncology Rehabilitation and Exercise Programme BEHAVIORAL

Participants randomised to the CORE programme will receive exercise training that is analogous to cardiac rehabilitation, but Exercise Physiologists will individualise each training program using the participants baseline CPET results to maximise adherence and improve the effectiveness of the training program beyond typical cardiac rehabilitation programs. An Exercise Physiologist will supervise two training sessions a week and monitor adherence to one other independent session at home each week for the first 12 weeks of the training program whilst exercise frequency, intensity, and time is progressively increased. Supervision of the exercise training will then be stepped down gradually after 12 weeks to a fortnightly check-in to encourage intervention adherence. Patients will be provided with a training calendar and objective tools for tracking physical activity (e.g. heart rate monitor and diary). Adherence will be monitored in real-time using a research web-based platform.

Also known as: Exercise Training

Cardio-Oncology Rehabilitation and Exercise Programme

Eligibility Criteria

• Age: 45 Years - 75 Years
• Gender Eligibility Details: Cisgender females.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female
• Aged 45 - 75 years old at study enrolment
• Diagnosed with stage 1 - 3 breast cancer 5 - 10 years prior to study enrolment
• Have received potentially toxic chemotherapy, including:
• Anthracycline (any dose)
• Trastuzumab (Herceptin) in breast-cancer with the HER2 mutation OR
• Tyrosine kinase inhibitors (e.g. sunitinib) OR
• Left chest radiotherapy
• ≥ 1 'traditional' CVD risk factor (I.e., Hypertension, dyslipidaemia, diabetes, obesity, smoking or family history of CVD) (Mehta et al., 2023)
• 'Physically inactive', not meeting Australian physical activity guidelines for adults or regularly participating in structured exercise training (Care, 2024).
• Eligible for Medicare
• Willing to provide written informed consent to participate in the study

You may not qualify if:

• Diagnosed CVD or stage B heart failure
• Diagnosed neurocognitive or cerebrovascular disease
• Diagnosed atrial fibrillation or cardiac arrythmia
• BMI ≤ 18.4 kg∙m2
• Any other contraindications to exercise testing and training that make participation in this study unsafe, determined through medical screening
• Unable to speak and understand the English language
• Contraindication to brain MRI
• Participating in another clinical research trial where randomized treatment would be unacceptable
• Oncologic (or other) life expectancy ≤ 12 months or any other medical condition (including pregnancy) that results in the belief (deemed by the Principal Investigator) that it is not appropriate for the patient to participate in this trial.

Sponsors & Collaborators

• Baker Heart and Diabetes Institute: lead

Study Sites (1)

Baker Heart and Diabetes Institute

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Exercise

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Erin Howden, A/Professor

  Baker Heart and Diabetes Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Howden, A/Professor

CONTACT

+61 38532 1861; erin.howden@baker.edu.au

Jack S Talbot, PhD

CONTACT

+61385321182; jack.talbot@baker.edu.au

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: SPONSOR

Study Record Dates

• First Submitted: March 20, 2025
• First Posted: April 13, 2025
• Study Start: November 3, 2025
• Primary Completion (Estimated): July 6, 2026
• Study Completion (Estimated): August 29, 2026
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal may request access to the data from the principal investigator of the study (A/Professor Erin Howden). Proposals should be directed to erin.howden@baker.edu.au initially. Data requestors will also need to sign a data sharing agreement with the Baker Heart and Diabetes Institute. This contract will be reviewed by the Baker Heart and Diabetes Institute's Contracts and Compliance Manager.

Locations

AU (1)