Exercise Preconditioning in Ovarian Cancer

Sponsor

University of Virginia (Other)

Overall Status

Recruiting

CT.gov ID

NCT05029154

Collaborator

(none)

Enrollment

Location

Arms

11.3

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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, peripheral neuropathy, and quality of life.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Behavioral: High intensity interval exercise Behavioral: Attention control	N/A

Detailed Description

While survivorship for those diagnosed with epithelial ovarian cancer has continued to improve, the significant off target effects of adjuvant and neoadjuvant chemotherapy have become more prominent. These off-target effects include increased risk of cardiovascular disease, neuropathy, and decreased quality of life. Exercise initiated prior to chemotherapy induction and continued through treatment has promise in terms of preserving VO2peak and potentially mitigating the negative cardiovascular and neuropathic effects of chemotherapy. The goal of this study is to examine the effects of initiating exercise prior to any oncologic therapy and sustaining this exercise paradigm in newly diagnosed women with ovarian cancer who are undergoing initial surgery and chemotherapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

27 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Two-arm randomized control trialTwo-arm randomized control trial

Masking:

Single (Outcomes Assessor)

Masking Description:

Due to the nature of the intervention (i.e. exercise training), participants and study team members cannot be blinded. However, outcomes assessment will be carried out in a blinded fashion.

Primary Purpose:

Prevention

Official Title:

Effect of Exercise Preconditioning in Ovarian Cancer on Treatment-Related Cardiotoxicity

Actual Study Start Date :

Oct 21, 2021

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Oct 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Exercise Patients in the exercise group will perform interval training 3 days per week.	Behavioral: High intensity interval exercise Patients in the exercise group will perform 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. Patients will undergo 2 initial training sessions at the exercise physiology core lab. All exercise will consist of stationary cycling to avoid discomfort associated with abdominal surgery as well as stress to the incision and help reduce fall risk. Study investigators will check in weekly with participants and remotely track exercise data and compliance via the Fitbit app.
Placebo Comparator: Attention Control Physical activity education and physical activity monitoring.	Behavioral: Attention control Patients in the control group (physical activity education and physical activity monitoring) will receive counseling regarding the benefits of physical activity during chemotherapy treatment. During the intervention, participants will receive a weekly phone call to discuss their physical activity and remind them to engage in physical activity. Patients will be given a goal of working up to 30 minutes of exercise daily. Subjects will be urged to increase daily step counts by 250-500 steps/day. Physical activity will be objectively assessed and made available to the participant using a Fitbit.

Arm

Intervention/Treatment

Experimental: Exercise

Patients in the exercise group will perform interval training 3 days per week.

Behavioral: High intensity interval exercise

Patients in the exercise group will perform 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. Patients will undergo 2 initial training sessions at the exercise physiology core lab. All exercise will consist of stationary cycling to avoid discomfort associated with abdominal surgery as well as stress to the incision and help reduce fall risk. Study investigators will check in weekly with participants and remotely track exercise data and compliance via the Fitbit app.

Placebo Comparator: Attention Control

Physical activity education and physical activity monitoring.

Behavioral: Attention control

Patients in the control group (physical activity education and physical activity monitoring) will receive counseling regarding the benefits of physical activity during chemotherapy treatment. During the intervention, participants will receive a weekly phone call to discuss their physical activity and remind them to engage in physical activity. Patients will be given a goal of working up to 30 minutes of exercise daily. Subjects will be urged to increase daily step counts by 250-500 steps/day. Physical activity will be objectively assessed and made available to the participant using a Fitbit.

Outcome Measures

Primary Outcome Measures

VO2 Peak [22 weeks]
Change in VO2peak (L/min) measured at pre-surgery, pre-chemotherapy, and post chemotherapy

Secondary Outcome Measures

Global Longitudinal Strain [22 weeks]
Global longitudinal strain (%) will be used to assess changes in cardiac contractile function and be measured by echocardiogram at pre-surgery, pre-chemotherapy, and post-chemotherapy
Ejection Fraction [22 weeks]
Ejection fraction (%) will be used to assess changes in cardiac contractile function and be measured by echocardiogram at pre-surgery, pre-chemotherapy, and post-chemotherapy
Diastolic Function [22 weeks]
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-surgery, pre-chemotherapy, and post-chemotherapy
Brachial Artery Endothelium-Dependent Flow-Mediated Dilation [22 weeks]
Changes in endothelial function as measured by brachial artery endothelium-dependent flow-mediated dilation (%) at pre-surgery, pre-chemotherapy, and post-chemotherapy
Carotid-Femoral Pulse Wave Velocity [22 weeks]
Changes in arterial stiffness as measured by carotid-femoral pulse wave velocity (m/s) at pre-surgery, pre-chemotherapy, and post-chemotherapy
Blood pressure [22 weeks]
Changes in measures of central and brachial blood pressure (mmHg) at pre-surgery, pre-chemotherapy, and post-chemotherapy
Peripheral Neuropathy [22 weeks]
A Neuropen will be used to assess for peripheral neuropathy via changes in perception to pressure prior to chemotherapy, at cycle 4, and after cycle 6.
Peripheral Neuropathy as assessed by the FACT-GOG-NTX Questionnaire [22 weeks]
The functional assessment of cancer therapy/gynecologic oncology group- neurotoxicity (FACT-GOG-NTX) questionnaire is used to assess symptoms of peripheral neuropathy. This 38 item questionnaire utilizes the same questions as the FACT questionnaire with 11 questions specific to peripheral neuropathy. A 5 point Likert scale is used for each question and subscores are added together with high scores indicating better quality of life
Health Related Quality of Life as Measured by the FACT-O Questionnaire [22 weeks]
The functional assessment of cancer therapy- ovarian cancer(FACT-O) questionnaire is used to assess health-related quality of life specific to cancer and includes a subscale for ovarian cancer. This 38 item questionnaire utilizes the same questions as the FACT questionnaire with 12 questions specific to ovarian cancer. A 5 point Likert scale is used for each question and subscores are added together with high scores indicating better quality of life
Quality of Life as Assessed by the Short Form Health Survey (SF-36) [22 weeks]
The Short Form Health survey is a 36 item questionnaire that is used to measure general health and quality of life. Responses in each section are scored on a scale of 0-100 (with 100 indicating good health) and averaged together for each subscale score.

Other Outcome Measures

NTproBNP [22 weeks]
Assess changes in NTproBNP (pg/ml) as a biomarker of myocardial strain at pre-surgery, pre-chemotherapy, and post-chemotherapy
Inflammation [22 weeks]
C-reactive protein (mg/dl) will be used as a biomarker for inflammation to be measured at pre-surgery, pre-chemotherapy, and post-chemotherapy
Lipids [22 weeks]
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-surgery, pre-chemotherapy, and post-chemotherapy
Insulin [22 weeks]
Fasting insulin levels (U/ml) will be tested to assess changes in cardiometabolic health at all 3 time points
Fasting Blood Glucose [22 weeks]
Fasting blood glucose levels (mg/dl) will be tested to assess changes in cardiometabolic health at pre-surgery, pre-chemotherapy, and post-chemotherapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years or over
Presumed diagnosis of ovarian cancer and a planned chemotherapy regimen of a taxane and carboplatin with or without VEGF inhibition
Physician clearance for exercise training

Exclusion Criteria:

Any patient unable/unwilling to cooperate with all study protocols
Cancer recurrence
Previous treatment with chemotherapy in the last 5-years
Medical/orthopedic co-morbidities that preclude exercise training
Significant heart, liver, kidney, blood, or respiratory disease precluding exercise participation
Peripheral vascular disease
Acute infectious disease or history of chronic infections