The Effects of Two Exercise Interventions on Breast Cancer Patients Undergoing Cardiotoxic Chemotherapies

A Feasibility Study to Examine Two Remotely-monitored Exercise Interventions on Breast Cancer Patients Undergoing Cardiotoxic Chemotherapies

The purpose of this study is to determine if exercise preconditioning can mitigate the off target effects of chemotherapy treatment on measures of cardiovascular function, inflammatory responses, and quality of life.

Study Overview

• Status: Recruiting
• Conditions: Cardiovascular Diseases; Breast Cancer; Cardiotoxicity
• Intervention / Treatment: Behavioral: High Intensity Interval Exercise; Behavioral: Moderate Intensity Walking

Detailed Description

Breast cancer is the most common malignancy affecting women in the US and survivors experience long-term health effects of chemotherapy. Exercise training is an efficacious treatment for preserving functional capacity and has shown promise in mitigating cardiac toxicity of breast cancer chemotherapy. However, supervised exercise is not a practical solution for all breast cancer survivors, as medically monitored exercise facilities are poorly dispersed in the US and poorly utilized by cancer patients. To improve reach of these programs, remotely monitoring exercise sessions may be necessary. However, effects of remotely-monitored exercise conditioning before and during adjuvant/neoadjuvant chemotherapy on cardiotoxic outcomes are unknown. Our study aims to address this gap by testing the feasibility of two types of remotely-monitored exercise interventions, an exercise bicycle intervention compared to a brisk walking intervention, in 20 UVA Breast Cancer Clinic patients undergoing cardiotoxic chemotherapies. Remotely-monitored exercise training will start one week prior to chemotherapy (preconditioning) and continue throughout adjuvant or neoadjuvant chemotherapy (which is typically 4 months in duration). Our multidisciplinary research team proposes four aims: 1) Determine the extent to which eligible patients can be successfully recruited, randomized, and retained; 2) Assess VO2peak, echocardiography derived left ventricular ejection fraction and left ventricular global longitudinal strain among these patients at baseline and at ~4 months; 3) Examine treatment engagement and intervention acceptability; and 4) Explore the relationship between engagement in the exercise training and psychosocial function.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Siddhartha S Angadi, PhD; Phone Number: 434-243-7466; Email: ssa2w@virginia.edu
• Study Contact Backup: Name: Zach Leicht, MS; Phone Number: 434-243-8677; Email: njn3wg@virginia.edu

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia University Hospital
      • Contact: Siddhartha S Angadi, PhD
      • Contact: Zach Leicht, MS; Email: njn3wg@virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or over
• diagnosis of breast cancer (Stage I-III or IV with minimal burden) and prescribed chemotherapy (TC (Docetaxel/Cyclophosphamide), AC (Doxorubicin/Cyclophosphamide followed by Paclitaxel), TCHP (Docetaxel, Carboplatin, Trastuzumab, Pertuzumab), TCH (Docetaxel/Carboplatin/Trastuzumab) with or without Pembrolizumab)
• Physician clearance for exercise training
• Speak/understand English

Exclusion Criteria:

• previous treatment with cardiotoxic chemotherapy
• medical/orthopedic comorbidities that preclude stationary cycling
• significant cardiac/renal/hepatic/hematological/pulmonary disease precluding exercise training
• unstable angina or myocardial infarction within 4-weeks prior to treatment
• complex ventricular arrhythmias or New York Heart Association class IV symptoms
• symptomatic severe aortic stenosis
• acute pulmonary embolus
• acute myocarditis
• History of untreated high-risk proliferative retinopathy
• History of retinal hemorrhage
• uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood pressure > 120 mm Hg)
• severe baseline electrolyte abnormalities
• medication non-compliance
• uncontrolled metabolic disease (diabetes with fasting blood sugar >300 mg/dl, thyrotoxicosis, myxedema)
• symptomatic peripheral vascular disease
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Intensity Interval Exercise; Subjects will receive a recumbent bike to be delivered and assembled to their home as well as a heart rate monitor and activity tracker. Subjects will undergo high intensity interval exercise 3 days a week, with the goal of achieving 85-90% of their heart rate max. Subjects will also be receiving text messages, phone calls, and emails from study staff to gauge and encourage subject participation and physical activity.	Behavioral: High Intensity Interval Exercise; Patients in the Cycling Intervention arm will undergo two training sessions at the exercise physiology core lab to ensure participants understand the intervention exercise protocol and can safely perform it at home. The Participants will perform high intensity interval training (HIIT) 3 days per week, with each session consisting of four, 4-min intervals at 85-90% peak heart rate (PHR), separated by 3 min at 50% PHR. Each training session will begin with a 10-minute warm-up at 50% of PHR and end with a 5-min cool down at 50% PHR. Subjects will then perform this exercise training at their own homes using recumbent exercise bikes provided by the investigators for that purpose. Study investigators will check in up to weekly with participants and remotely track exercise data and compliance via activity tracker.
Experimental: Moderate Intensity Walking; Subjects allocated to moderate intensity walking will be given a gift card to purchase a paid of running shoes. A chest-based heart rate monitor and an activity tracker watch will be provided. Subjects will aim to achieve 150 minutes a week of moderate intensity walking. Subjects will also be receiving text messages, phone calls, and emails from study staff to gauge and encourage subject participation and physical activity.	Behavioral: Moderate Intensity Walking; Patients will undergo two familiarization training sessions in the exercise physiology core lab to ensure participants understands the walking intervention and can properly gauge intensity. Participants will be asked to walk briskly or jog so they achieve a moderate intensity (70-75% of the maximal heart rate achieved during the VO2peak test). The goal for participants in this condition will be to accumulate at least 150-minutes per week at this heart rate by brisk walking or jogging. Participants will also receive a gift card to be used to purchase a pair of walking shoes to facilitate their engagement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subject Retention Percentage	This is a feasibility study designed to determine the extent to which eligible patients can be successfully recruited, randomized, and retained. Endpoint data will be used to justify and provide point estimates for a fully powered study. Retention will be measured as a percentage of those enrolled who complete the study interventions.	22 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VO2peak	Change in VO2peak (L/min) measured at pre-chemotherapy and post chemotherapy	22 Weeks
Global Longitudinal Strain	Global longitudinal strain (%) will be used to assess changes in cardiac contractile function and be measured by echocardiogram at pre-chemotherapy and post-chemotherapy	22 Weeks
Ejection Fraction	Ejection fraction (%) will be used to assess changes in cardiac contractile function and be measured by echocardiogram at pre-chemotherapy and post-chemotherapy	22 Weeks
Diastolic Function	E' and A' (cm/s) will be used to calculate the E'/A' ratio to assess for diastolic dysfunction and be measured by echocardiogram at pre-chemotherapy and post-chemotherapy	22 Weeks
Brachial Artery Endothelium-Dependent Flow-Mediated Dilation	Changes in endothelial function as measured by brachial artery endothelium-dependent flow-mediated dilation (%) at pre-chemotherapy and post-chemotherapy	22 Weeks
Carotid-Femoral Pulse Wave Velocity	Changes in arterial stiffness as measured by carotid-femoral pulse wave velocity (m/s) at pre-chemotherapy and post-chemotherapy	22 Weeks
Blood pressure	Brachial systolic and diastolic blood pressures (mmHg) will be measured at baseline and post-chemotherapy.	22 Weeks
Lipid panels	A lipid panel will be performed to measure total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoprotein (mg/dl) to assess changes in cardiometabolic health at pre-chemotherapy and post-chemotherapy	22 Weeks
Inflammation/Immune cell concentrations in peripheral circulation.	Various markers of inflammation and immune cells will be measured at baseline, pre-chemo (following exercise pre-conditioning), midway through patient's prescribed treatment, and post-intervention to determine changes.	22 Weeks

Collaborators and Investigators

• Sponsor: University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): January 15, 2025
• Study Completion (Estimated): March 15, 2025

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 9, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: chemotherapy; cardiotoxicity; cardiorespiratory fitness
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Heart Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Wounds and Injuries; Breast Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cardiovascular Diseases; Breast Neoplasms; Cardiotoxicity
• Other Study ID Numbers: 220287

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No