Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Nervous System Diseases

Rare Diseases

Lymphoma

Autonomic Nervous System Diseases

Primary Dysautonomias

Lymphosarcoma

* Ivabradine will be administered for a total of 6 weeks
* Ivabradine is taken orally twice daily
* Dosage will be adjusted according to physician determination

* Placebo will be administered for a total of 6 weeks
* Placebo is taken orally twice daily
* Dosage will be adjusted according to physician determination

lower heart rate in heart failure patients.

Ivabradine

Procedure prescribed to compare the active effect of a medicine.

Placebo Oral Tablet

Anju Nohria, MD

This study will explore whether ivabradine lowers heart rate, and thus improves exercise capacity, in survivors of lymphoma who have an elevated resting heart rate as a side effect of prior radiation treatment.

The drugs involved in this study are:

* Ivabradine
* Placebo

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

This research study is a Pilot Study, which is the first time investigators are examining this study intervention for this particular problem.

In this research study, the investigators are studying a drug called ivabradine. The investigators are exploring whether ivabradine can be used to reduce heart rate, increase exercise duration, and improve quality of life in survivors of lymphoma who received radiation to their chest as a part of their cancer treatment.

The U.S. Food and Drug Administration (FDA) has not approved ivabradine for this specific disease, but it has approved the drug as an oral medication to lower heart rate in heart failure patients.

Survivors of lymphoma who were treated with neck and/or chest radiation can have an elevated resting heart rate and an abnormal rate of decline in their heart rate after exercise, also known as cardiac autonomic dysfunction. These abnormalities can limit exercise duration and worsen quality of life in some radiation treated survivors of lymphoma

Ivabradine in the Management of Cardiac Autonomic Dysfunction Associated With Thoracic Radiation Therapy.

Calculate the change in cardiac autonomic function (from cardiac autonomic function testing) from baseline to 6 weeks in one half of the patients in the study (n=30)

Calculate the change in health related quality of life (from SF-36 quality of life surveys) from baseline to 6 weeks for each patient in the study (n=60)

Calculate the change in resting HR (from Holter monitor data) from baseline to 6 weeks for each patient in the study. Then compare the median change with ivabradine to the median change with placebo.

Calculate the change in exercise duration (from exercise treadmill stress tests) from baseline to 6 weeks for each patient in the study. Then compare the median change in exercise duration with ivabradine to the median change in exercise duration with placebo.

Amgen

Dana-Farber Cancer Institute

Assistant Professor in Internal Medicine

* Ivabradine will be administered for a total of 6 weeks
* Ivabradine is taken orally twice daily
* Dosage will be adjusted according to physician determination

Ivabradine: lower heart rate in heart failure patients.

* Placebo will be administered for a total of 6 weeks
* Placebo is taken orally twice daily
* Dosage will be adjusted according to physician determination

Placebo Oral Tablet: Procedure prescribed to compare the active effect of a medicine.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Beta-blocker at baseline

Baseline echo data not available in 2 pts randomized to the ivabradine group

Ejection Fraction, %

Resting heart rate

Dr. Anju Nohria

Analyzed all patients who had data available at baseline and at 6 weeks

To Investigate Whether Ivabradine Lowers Resting HR, Compared To Placebo, In Survivors Of Lymphoma

To Evaluate Whether Ivabradine Improves Exercise Duration, Compared To Placebo, In Survivors Of Lymphoma

To Evaluate Whether Ivabradine Improves Additional Markers of Cardiac Sympatho-vagal Balance, Compared To Placebo, In Survivors Of Lymphoma

To Evaluate Whether Ivabradine Improves Health Related Quality Of Life Compared To Placebo, In Survivors Of Lymphoma

Overall Study

Skin and Connective Tissue Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Substance Related Disorders

Wounds and Injuries

Breast Neoplasms

Cardiotoxicity

Breast Diseases

Skin Diseases

Heart Diseases

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

Radiation Injuries

Participants will continue with their daily life and usual care.

Participants will participate in a physical exercise program with a preplanned intensity progression.

Participants will participate in a physical exercise program guide by participants' daily heart rate variability to plan the intensity progression.

The physical exercise programme will last 16 weeks where participants will do three weekly sessions of 60 minutes, approximately. In these training sessions, cardiovascular and strength components will be worked out, planned from moderate to high intensity in the TEG and unique high intensity in the HRVG. The training programme will be divided into three mesocycles from neuromuscular adaptation to reach, in last period, the highest loads and cardiovascular levels. Each session will include a warm-up, a main part and a cool-down with stretching and mobility exercises.

The difference between the interventions of the HRVG and TEG will be in the planning of the intensity of the cardiovascular exercises and the weight to be lifted in the strength exercises. The first session of both programmes will have the same intensity but depending on how the heart rate variability of the HRVG patients reacts to, the weight and the intensity will be individualised each day.

Physical exercise program

Ana Myriam Lavín-Pérez

Alfonso Jiménez, Professor

Daniel Collado-Mateo, PhD

Breast cancer is a chronic disease that has seen a boom in research into its treatments, improvements and effects in recent decades. These advances have also highlighted the need to use physical exercise as a countermeasure to reduce the cardiotoxicity of pharmacological treatments. Patients need a correct daily individualisation of the exercise dose necessary to produce the physiological, physical and psychological benefits. To this end, the present study will use, in a novel way in this population, heart rate variability (HRV) as a measure of training prescription. The primary objective of this randomised clinical trial is to analyse the effects of a physical exercise programme planned according to daily HRV in breast cancer patients after chemotherapy treatment. For this purpose, a 16-week intervention will be carried out with 90 breast cancer patients distributed in 3 groups (control group, conventional preprogrammed physical exercise training group and physical exercise group with HRV daily programming). Cardiorespiratory capacity, strength, flexibility, agility, balance, body composition, quality of life, fatigue, functionality, self-esteem, anxiety and depression of patients before and after the intervention will be evaluated in order to compare the effects of exercise and its programming.

The intervention of 16 weeks will include exercise programmes of 48 sessions conducted three times per week for two of the three study groups. These groups will be: a group participating in a conventional training programme, based on a preplanned intensity progression; and, a group of participants involved in an exercise programme which will vary the exercise intensity regarding patients' daily Heart Rate Variability. Each session will include a warm-up, the main part of cardiovascular and strength training and a cool-down including stretching exercises.

All the participants will be evaluated before and after the intervention measuring clinical, physical and psychosocial assessments. The clinical variables will be evaluated in patients' reference hospital and will involve medical history registers, cardiotoxicity variables, blood analysis and inflammatory factors measures. Physical and psychosocial variables measurement will be carried out in a sports centre and will include the assessment of: body composition, heart rate variability, cardiorespiratory capacity, upper and lower extremities' strength and flexibility, agility and balance, quality of life, fatigue, functionality, life satisfaction, self-esteem, anxiety and depression, shoulder mobility perception, kinesiophobia, physical activity level and exercise motivation.

Exercise Prescription Guided by Heart Rate Variability in Breast Cancer Patients

Effects of Physical Exercise, and Its Prescription Guided by Heart Rate Variability, on the Cardiotoxicity, Physical and Psychological Health of Breast Cancer Patients

A haemogram will be carried out to analyse patients' Troponin I and T to detect their cardiotoxicity levels. Troponin results will be reported in ng/L.

A haemogram will be carried out to analyse patients' Troponin I and T to detect their cardiotoxicity levels and the change produced after the intervention. Troponin results will be reported in ng/L.

A haemogram will be carried out to analyse patients' Troponin I and T to detect their cardiotoxicity levels and the changes produced 3 months after the intervention. Troponin results will be reported in ng/L.

A haemogram will be carried out to analyse patients' Troponin I and T to detect their cardiotoxicity levels and the changes produced 6 months after the intervention. Troponin results will be reported in ng/L.

A haemogram will be carried out to analyse patients' BNP to assess their cardiotoxicity levels. BNP results will be reported in pg/ml.

A haemogram will be carried out to analyse patients' BNP to assess their cardiotoxicity levels and the change produced after the intervention. BNP results will be reported in pg/ml.

A haemogram will be carried out to analyse patients' BNP to assess their cardiotoxicity levels and the change produced 3 after the intervention. BNP results will be reported in pg/ml.

A haemogram will be carried out to analyse patients' BNP to assess their cardiotoxicity levels and the change produced 6 after the intervention. BNP results will be reported in pg/ml.

An echocardiogram will be performed to measure left ventricular systolic and diastolic volume in mL.

An echocardiogram will be performed to measure left ventricular systolic and diastolic volume in mL and it changes after the intervention.

An echocardiogram will be performed to measure left ventricular systolic and diastolic volume in mL and it changes 3 months after the intervention.

An echocardiogram will be performed to measure left ventricular systolic and diastolic volume in mL and it changes 6 months after the intervention.

By an echocardiogram, patients' % of LVEF will be assessed due to its possible modification caused by cardiotoxicity.

By an echocardiogram, patients' % of LVEF will be assessed to measure its results and its change after the intervention.

By an echocardiogram, patients' % of LVEF will be assessed to measure its results and its change 3 months after the intervention.

By an echocardiogram, patients' % of LVEF will be assessed to measure its results and its change 6 months after the intervention.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the standard deviation time domains of all RR intervals (SDNN) in ms, the mean ad all RR intervals in ms and the root mean square of the sum of squared RR interval differences in ms (RMSSD) will be recorded.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the standard deviation time domains of all RR intervals (SDNN) in ms, the mean ad all RR intervals in ms and the root mean square of the sum of squared RR interval differences in ms (RMSSD) will be recorded after the intervention.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the standard deviation time domains of all RR intervals (SDNN) in ms, the mean ad all RR intervals in ms and the root mean square of the sum of squared RR interval differences in ms (RMSSD) will be recorded 3 months after the intervention.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the standard deviation time domains of all RR intervals (SDNN) in ms, the mean ad all RR intervals in ms and the root mean square of the sum of squared RR interval differences in ms (RMSSD) will be recorded 6 months after the intervention.

Daily heart rate variability will be measured using the HRV4Training application, a validated mobile application that allows HRV values to be obtained by photoplethysmography (rMSSD, SDNN, AVNN, pNN50 and heart rate).

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the frequency measures of low frequency (LF, 0.04-0.15 Hz) in ms2 and n.u, high frequency (HF, 0.15-0.4 Hz) ms2 and n.u, total power in ms2 and LF/HF ratio will be calculated.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the frequency measures of low frequency (LF, 0.04-0.15 Hz) in ms2 and n.u, high frequency (HF, 0.15-0.4 Hz) ms2 and n.u, total power in ms2 and LF/HF ratio will be calculated after intervention.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the frequency measures of low frequency (LF, 0.04-0.15 Hz) in ms2 and n.u, high frequency (HF, 0.15-0.4 Hz) ms2 and n.u, total power in ms2 and LF/HF ratio will be calculated 3 months after the intervention.

The assessment of heart rate variability will be performed with a Polar chest strap and electrocardiogram. Participants will remain in the supine position for 10 minutes to correctly obtain 5 minutes of a stable signal. After removal of artefacts, the frequency measures of low frequency (LF, 0.04-0.15 Hz) in ms2 and n.u, high frequency (HF, 0.15-0.4 Hz) ms2 and n.u, total power in ms2 and LF/HF ratio will be calculated 6 months after the intervention.

Daily heart rate variability will be measured using the HRV4Training application, a validated mobile application that allows HRV values to be obtained by photoplethysmography (LF, HF, TP, LF/HF and recovery points)

A resting electrocardiogram will be used to obtain patients' normal values for heart rate measurements in bpm, I-axis and aVF, Q-T interval, QRS complex, S-T segment and T-wave, in ms. Moreover, resting heart rate will be assessed by a Polar chest band.

A resting electrocardiogram will be used to obtain patients' normal values for heart rate measurements in bpm, I-axis and aVF, Q-T interval, QRS complex, S-T segment and T-wave, in ms, and get after intervention results. Moreover, resting heart rate will be assessed by a Polar chest band.

A resting electrocardiogram will be used to obtain patients' normal values for heart rate measurements in bpm, I-axis and aVF, Q-T interval, QRS complex, S-T segment and T-wave, in ms, and get its results 3 months after the intervention. Moreover, resting heart rate will be assessed by a Polar chest band.

A resting electrocardiogram will be used to obtain patients' normal values for heart rate measurements in bpm, I-axis and aVF, Q-T interval, QRS complex, S-T segment and T-wave, in ms, and get its results 6 months after the intervention. Moreover, resting heart rate will be assessed by a Polar chest band.

Through a blood analysis TFN, in pg/mL, will be measured to evaluate patients' inflammation.

Through a blood analysis TFN, in pg/mL, will be measured to evaluate patients' inflammation after the intervention.

Through a blood analysis TFN, in pg/mL, will be measured to evaluate patients' inflammation 3 months after the intervention.

Through a blood analysis TFN, in pg/mL, will be measured to evaluate patients' inflammation 6 months after the intervention.

The inflammation will be assessed by blood interleukins will include IL-6, IL-8, IL-1b, IL-1ra and IL-10 values, in pg/m.

The inflammation will be assessed by blood interleukins will include IL-6, IL-8, IL-1b, IL-1ra and IL-10 values, in pg/m, immediately after the intervention.

The inflammation will be assessed by blood interleukins will include IL-6, IL-8, IL-1b, IL-1 and IL-10 values, in pg/m, 3 months after the intervention.

The inflammation will be assessed by blood interleukins will include IL-6, IL-8, IL-1b, IL-1ra and IL-10 values, in pg/m, 6 months after the intervention.

C-reactive protein (CRP), measured in mg/L will be evaluated to get patients' pro-inflammatory data.

C-reactive protein (CRP), measured in mg/L will be evaluated to get patients' pro-inflammatory data after the intervention.

C-reactive protein (CRP), measured in mg/L will be evaluated to get patients' pro-inflammatory data 3 months after the intervention.

C-reactive protein (CRP), measured in mg/L will be evaluated to get patients' pro-inflammatory data 6 months after the intervention.

Monocyte chemotactic protein (MCP-1), measured in pg/mL will be evaluated to get patients' pro-inflammatory data.

Monocyte chemotactic protein (MCP-1), measured in pg/mL will be evaluated to get patients' pro-inflammatory data after the intervention.

Monocyte chemotactic protein (MCP-1), measured in pg/mL will be evaluated to get patients pro-inflammatory data 3 months after the intervention.

Monocyte chemotactic protein (MCP-1), measured in pg/mL will be evaluated to get patients pro-inflammatory data 6 months after the intervention.

Glucose, in mg/dl, will be measure through a blood test due to be related to cancer prognosis and cardiovascular risk.

Glucose, in mg/dl, will be measure after intervention through a blood test due to be related to cancer prognosis and cardiovascular risk.

Low-density lipoprotein and high-density lipoprotein, measured in mg/dL, will be assessed by a blood test due to be related to cancer prognosis and cardiovascular risk.

Low-density lipoprotein and high-density lipoprotein, measured in mg/dL, will be measure after intervention by a blood test due to be related to cancer prognosis and cardiovascular risk.

Low-density lipoprotein and high-density, measured in mg/dL, will be measure 3 months after the intervention by a blood test due to be related to cancer prognosis and cardiovascular risk.

Low-density lipoprotein and high-density, measured in mg/dL, will be measure 6 months after the intervention by a blood test due to be related to cancer prognosis and cardiovascular risk.

Measurements of blood pressure will be performed using a validated oscillometer. Participants will remain at rest for five minutes before the assessment. They will place their left arm, on which the measurement will be taken, on the table so that the cuff is at the level of the heart, 2 cm from the elbow. In addition, any clothing that may alter the results shall be removed. Once in this position, the air tube of the cuff shall be placed on the front of the upper arm in line with the middle finger and the blue arrow on the cuff. Systolic and diastolic blood pressure data, measured in mmHg, shall be taken, and then the mean arterial pressure = (systolic blood pressure+ (2\*diastolic blood pressure))/3 shall be calculated.

Measurements of blood pressure after the intervention will be performed using a validated oscillometer. Participants will remain at rest for five minutes before the assessment. They will place their left arm, on which the measurement will be taken, on the table so that the cuff is at the level of the heart, 2 cm from the elbow. In addition, any clothing that may alter the results shall be removed. Once in this position, the air tube of the cuff shall be placed on the front of the upper arm in line with the middle finger and the blue arrow on the cuff. Systolic and diastolic blood pressure data, measured in mmHg, shall be taken, and then the mean arterial pressure = (systolic blood pressure+ (2\*diastolic blood pressure))/3 shall be calculated.

Measurements of blood pressure 3 months after the intervention will be performed using a validated oscillometer. Participants will remain at rest for five minutes before the assessment. They will place their left arm, on which the measurement will be taken, on the table so that the cuff is at the level of the heart, 2 cm from the elbow. In addition, any clothing that may alter the results shall be removed. Once in this position, the air tube of the cuff shall be placed on the front of the upper arm in line with the middle finger and the blue arrow on the cuff. Systolic and diastolic blood pressure data, measured in mmHg, shall be taken, and then the mean arterial pressure = (systolic blood pressure+ (2\*diastolic blood pressure))/3 shall be calculated.

Measurements of blood pressure 6 months after the intervention will be performed using a validated oscillometer. Participants will remain at rest for five minutes before the assessment. They will place their left arm, on which the measurement will be taken, on the table so that the cuff is at the level of the heart, 2 cm from the elbow. In addition, any clothing that may alter the results shall be removed. Once in this position, the air tube of the cuff shall be placed on the front of the upper arm in line with the middle finger and the blue arrow on the cuff. Systolic and diastolic blood pressure data, measured in mmHg, shall be taken, and then the mean arterial pressure = (systolic blood pressure+ (2\*diastolic blood pressure))/3 shall be calculated.

The weight assessment of body composition will be performed by impedance to obtain patients' global bodyweight, musculoskeletal mass, mineral mass, fat mass and upper and lower extremities segmental fat and lean mass weight. All the measures will be reported in kilograms.

The weight assessment of body composition after the intervention will be performed by impedance to obtain patients' global bodyweight, musculoskeletal mass, mineral mass, fat mass and upper and lower extremities segmental fat and lean mass weight. All the measures will be reported in kilograms.

The weight assessment of body composition 3 months after the intervention will be performed by impedance to obtain patients' global bodyweight, musculoskeletal mass, mineral mass, fat mass and upper and lower extremities segmental fat and lean mass weight. All the measures will be reported in kilograms.

The weight assessment of body composition 6 months after the intervention will be performed by impedance to obtain patients' global bodyweight, musculoskeletal mass, mineral mass, fat mass and upper and lower extremities segmental fat and lean mass weight. All the measures will be reported in kilograms

The assessment of the body fat percentage of the participants is a variable to be taken into consideration. Therefore, thought impedance patients' body fat percentage and upper and lower extremities segmental fat and lean mass percentages will be recorded.

The assessment of the body percentage of the participants is a variable to be taken into consideration. Therefore, thought impedance, patients' body fat percentage and upper and lower extremities segmental fat and lean mass percentages will be recorded after the intervention.

The assessment of the body percentage of the participants is a variable to be taken into consideration. Therefore, thought impedance, patients' body fat percentage and upper and lower extremities segmental fat and lean mass percentages will be recorded 3 months after the intervention.

The assessment of the body percentage of the participants is a variable to be taken into consideration. Therefore, thought impedance, patients' body fat percentage and upper and lower extremities segmental fat and lean mass percentages will be recorded 6 months after the intervention.

By employing also impedance body water evaluation, measured in liters, will be carried out.

By employing also impedance, body water evaluation, measured in liters, will be carried out after the intervention.

By employing also impedance, body water evaluation, measured in liters, will be carried out 3 months after the intervention.

By employing also impedance, body water evaluation, measured in liters, will be carried out 6 months after the intervention.

Patients' height and body perimeters will be assessed in centimeters. Especially, waist circumference, hip circumference, arm circumferences, leg circumferences will be measured following the guidelines set by the American College of Sports Medicine. Afterward, patients' height will be used together with their corresponding weight to calculate patients Body Mass Index.

Patients' height and body perimeters will be assessed in centimeters immediately after the intervention. Especially, waist circumference, hip circumference, arm circumferences, leg circumferences will be measured following the guidelines set by the American College of Sports Medicine. Afterward, patients' height will be used together with their corresponding weight to calculate patients Body Mass Index.

Patients' height and body perimeters will be assessed in centimeters 3 months after the end of the intervention. Especially, waist circumference, hip circumference, arm circumferences, leg circumferences will be measured following the guidelines set by the American College of Sports Medicine. Afterward, patients' height will be used together with their corresponding weight to calculate patients Body Mass Index.

Patients' height and body perimeters will be assessed in centimeters 6 months after the end of the intervention. Especially, waist circumference, hip circumference, arm circumferences, leg circumferences will be measured following the guidelines set by the American College of Sports Medicine. Afterward, patients' height will be used together with their corresponding weight to calculate patients Body Mass Index.

To record cardiorespiratory fitness, maximum heart rate and patients' perception of exertion, the Bruce incremental submaximal test (modified) was performed on a treadmill. During the test, the patients will wear a chest strap for heart rate monitoring. Thus, following the protocol created by Bruce, the treadmill will start with a 0% incline and a speed of 1.7 m/h which will be maintained for the first 3 minutes. Every 3 minutes, both the speed and the incline will be increased until the participants decide that their fatigue is too great to continue. At the end of the test, the recovery heart rate is recorded 1 minute after stopping the test to assess the recovery rate. Subsequently, the maximum oxygen consumption of each patient (VO2max = 2.282\* (time) + 8.545) will be calculated from the formula proposed by the creators.

To record cardiorespiratory fitness after the intervention, maximum heart rate and patients' perception of exertion, the Bruce incremental submaximal test (modified) was performed on a treadmill. During the test, the patients will wear a chest strap for heart rate monitoring. Thus, following the protocol created by Bruce, the treadmill will start with a 0% incline and a speed of 1.7 m/h which will be maintained for the first 3 minutes. Every 3 minutes, both the speed and the incline will be increased until the participants decide that their fatigue is too great to continue. At the end of the test, the recovery heart rate is recorded 1 minute after stopping the test to assess the recovery rate. Subsequently, the maximum oxygen consumption of each patient (VO2max = 2.282\* (time) + 8.545) will be calculated from the formula proposed by the creators.

To record cardiorespiratory fitness 3 months after the intervention, maximum heart rate and patients' perception of exertion, the Bruce incremental submaximal test (modified) was performed on a treadmill. During the test, the patients will wear a chest strap for heart rate monitoring. Thus, following the protocol created by Bruce, the treadmill will start with a 0% incline and a speed of 1.7 m/h which will be maintained for the first 3 minutes. Every 3 minutes, both the speed and the incline will be increased until the participants decide that their fatigue is too great to continue. At the end of the test, the recovery heart rate is recorded 1 minute after stopping the test to assess the recovery rate. Subsequently, the maximum oxygen consumption of each patient (VO2max = 2.282\* (time) + 8.545) will be calculated from the formula proposed by the creators.

To record cardiorespiratory fitness 6 months after the intervention, maximum heart rate and patients' perception of exertion, the Bruce incremental submaximal test (modified) was performed on a treadmill. During the test, the patients will wear a chest strap for heart rate monitoring. Thus, following the protocol created by Bruce, the treadmill will start with a 0% incline and a speed of 1.7 m/h which will be maintained for the first 3 minutes. Every 3 minutes, both the speed and the incline will be increased until the participants decide that their fatigue is too great to continue. At the end of the test, the recovery heart rate is recorded 1 minute after stopping the test to assess the recovery rate. Subsequently, the maximum oxygen consumption of each patient (VO2max = 2.282\* (time) + 8.545) will be calculated from the formula proposed by the creators.

Functional strength will be measure by the 30 seconds chair stand test. The patient will stand up, position herself fully stretched, and perform as many repetitions as possible in 30 seconds.

Functional strength will be measure by the 30 seconds chair stand test. The patient will stand up, positioning herself fully stretched, and perform as many repetitions as possible in 30 seconds.

The evaluation of maximal strength will be performed by using an encoder for the correct calculation of the Maximum Repetition (RM) from the speed and power generated by moving the weight vertically. The participants will perform 4 tests to assess the different muscular groups' strength (Back Squat Test, Deadlift Test, Lunge Test, Barbell Hip Thrust Test). Concretely, 4-5 repetitions will be performed with incremental weights where the speed of execution decreases.

The evaluation of maximal strength after the intervention will be performed by using an encoder for the correct calculation of the Maximum Repetition (RM) from the speed and power generated by moving the weight vertically. The participants will perform 4 tests to assess the different muscular groups' strength (Back Squat Test, Deadlift Test, Lunge Test, Barbell Hip Thrust Test). Concretely, 4-5 repetitions will be performed with incremental weights where the speed of execution decreases.

The evaluation of maximal strength 3 months after the intervention will be performed by using an encoder for the correct calculation of the Maximum Repetition (RM) from the speed and power generated by moving the weight vertically. The participants will perform 4 tests to assess the different muscular groups' strength (Back Squat Test, Deadlift Test, Lunge Test, Barbell Hip Thrust Test). Concretely, 4-5 repetitions will be performed with incremental weights where the speed of execution decreases.

The evaluation of maximal strength 6 months after the intervention will be performed by using an encoder for the correct calculation of the Maximum Repetition (RM) from the speed and power generated by moving the weight vertically. The participants will perform 4 tests to assess the different muscular groups' strength (Back Squat Test, Deadlift Test, Lunge Test, Barbell Hip Thrust Test). Concretely, 4-5 repetitions will be performed with incremental weights where the speed of execution decreases.

The force-power will be measured using a countermovement jump test (CMJ) and squat jump test (SJ). From these tests, the maximum force (N) and power (P) exerted during impulse and landing, flight time (ms) and jump height (cm) will be obtained. For the evaluation of the different variables indicated, different technologies will be used such as a jump platform and/or the recording of each of the jumps for subsequent analysis with the validated application of My Jump and Kinovea.

The after-intervention force-power will be measured using a countermovement jump test (CMJ) and squat jump test (SJ). From these tests, the maximum force (N) and power (P) exerted during impulse and landing, flight time (ms) and jump height (cm) will be obtained. For the evaluation of the different variables indicated, different technologies will be used such as a jump platform and/or the recording of each of the jumps for subsequent analysis with the validated application of My Jump and Kinovea.

The force-power 3 months after the intervention will be measured using a countermovement jump test (CMJ) and squat jump test (SJ). From these tests, the maximum force (N) and power (P) exerted during impulse and landing, flight time (ms) and jump height (cm) will be obtained. For the evaluation of the different variables indicated, different technologies will be used such as a jump platform and/or the recording of each of the jumps for subsequent analysis with the validated application of My Jump and Kinovea.

The force-power 6 months after the intervention will be measured using a countermovement jump test (CMJ) and squat jump test (SJ). From these tests, the maximum force (N) and power (P) exerted during impulse and landing, flight time (ms) and jump height (cm) will be obtained. For the evaluation of the different variables indicated, different technologies will be used such as a jump platform and/or the recording of each of the jumps for subsequent analysis with the validated application of My Jump and Kinovea.

The strength endurance of the patients will be measured utilizing the 30-second arm curl test reporting the maximum number of repetitions in 30 seconds.

The strength endurance of the patients after the intervention will be measured employing the 30-second arm curl test reporting the maximum number of repetitions in 30 seconds.

The strength endurance of the patients 3 months after the intervention will be measured utilizing the 30-second arm curl test reporting the maximum number of repetitions in 30 seconds.

The strength endurance of the patients 6 months after the intervention will be measured employing the 30-second arm curl test reporting the maximum number of repetitions in 30 seconds.

Maximal strength of different muscular group exercises will be assessed (chest press, shoulder press, bent over row, biceps curl with barbell, Triceps extension with barbell) based on the number of repetitions that the participants are able to perform. An encoder will be used to calculate the Maximum Repetition (RM) by the speed and power generated by moving the weight vertically.

Maximal strength of different muscular group exercises after the intervention will be assessed (chest press, shoulder press, bent over row, biceps curl with barbell, Triceps extension with barbell) based on the number of repetitions that the participants are able to perform. An encoder will be used to calculate the Maximum Repetition (RM) by the speed and power generated by moving the weight vertically.

Maximal strength of different muscular group exercises 3 months after the intervention will be assessed (chest press, shoulder press, bent over row, biceps curl with barbell, Triceps extension with barbell) based on the number of repetitions that the participants are able to perform. An encoder will be used to calculate the Maximum Repetition (RM) by the speed and power generated by moving the weight vertically.

Maximal strength of different muscular group exercises 6 months after the intervention will be assessed (chest press, shoulder press, bent over row, biceps curl with barbell, Triceps extension with barbell) based on the number of repetitions that the participants are able to perform. An encoder will be used to calculate the Maximum Repetition (RM) by the speed and power generated by moving the weight vertically.

The 8-foot up-and-go test will be employed to measure dynamic balance and agility, where the participants will get up from the chair and walk as fast as possible to the cone, placed 2,44 meters far away, and around the cone, back to the chair. The outcome measure will be the time spend in seconds.

The 8-foot up-and-go test will be employed to measure dynamic balance and agility after the intervention, where the participants will get up from the chair and walk as fast as possible to the cone, placed 2,44 meters far away, and around the cone, back to the chair. The outcome measure will be the time spend in seconds.

The 8-foot up-and-go test will be employed to measure dynamic balance and agility 3 months after the intervention, where the participants will get up from the chair and walk as fast as possible to the cone, placed 2,44 meters far away, and around the cone, back to the chair. The outcome measure will be the time spend in seconds.

The 8-foot up-and-go test will be employed to measure dynamic balance and agility 6 months after the intervention, where the participants will get up from the chair and walk as fast as possible to the cone, placed 2,44 meters far away, and around the cone, back to the chair. The outcome measure will be the time spend in seconds.

The one-leg stand test from the adults ALHPA battery will assess static balance. For this purpose, the patient will be placed in monopodal support, placing the sole on the inside of the knee. The time reached, in seconds, without touching the group with the other foot will be recorded.

The one-leg stand test from the adults ALHPA battery will assess static balance after the intervention. For this purpose, the patient will be placed in monopodal support, placing the sole of the foot on the inside of the knee. The time reached, in seconds, without touching the group with the other foot will be recorded.

The one-leg stand test from the adults ALHPA battery will assess static balance 3 months after the intervention. For this purpose, the patient will be placed in monopodal support, placing the sole on the inside of the knee. The time reached, in seconds, without touching the group with the other foot will be recorded.

The one-leg stand test from the adults ALHPA battery will assess static balance 6 months after the intervention. For this purpose, the patient will be placed in monopodal support, placing the sole of the foot on the inside of the knee. The time reached, in seconds, without touching the group with the other foot will be recorded

Flexibility will be assessed using the Back scratch test, previously used in breast cancer patients and belonging to the Senior Fitness Test battery. During the test, participants will stand upright and try to reach over their head, with their arm in flexion and external rotation, to touch their other hand, which will be placed on their back in a supine position with the arm flexed. The centimeters left or passed from one hand to the other will be noted.

Flexibility after the intervention will be assessed using the Back scratch test, previously used in breast cancer patients and belonging to the Senior Fitness Test battery. During the test, participants will stand upright and try to reach over their head, with their arm in flexion and external rotation, to touch their other hand, which will be placed on their back in a supine position with the arm flexed. The centimeters left or passed from one hand to the other will be noted.

Flexibility 3 months after the intervention will be assessed using the Back scratch test, previously used in breast cancer patients and belonging to the Senior Fitness Test battery. During the test, participants will stand upright and try to reach over their head, with their arm in flexion and external rotation, to touch their other hand, which will be placed on their back in a supine position with the arm flexed. The centimeters left or passed from one hand to the other will be noted.

Flexibility 6 months after the intervention will be assessed using the Back scratch test, previously used in breast cancer patients and belonging to the Senior Fitness Test battery. During the test, participants will stand upright and try to reach over their head, with their arm in flexion and external rotation, to touch their other hand, which will be placed on their back in a supine position with the arm flexed. The centimeters left or passed from one hand to the other will be noted.

Hamstring flexibility will be measured using the V Sit and Reach test where the participant will be seated on the floor with knees fully extended and feet 30 cm apart. A tape measure will be placed on the floor, equidistant between the feet, placing the 0 cm in line with the heels. Pressing the palms of the hands together and keeping the elbows fully extended, the participants shall bend their trunk as far as possible over the tape measure. The results will be expressed in centimeters reporting the distance left or passed from the feet.

Hamstring flexibility after the intervention will be measured using the V Sit and Reach test where the participant will be seated on the floor with knees fully extended and feet 30 cm apart. A tape measure will be placed on the floor, equidistant between the feet, placing the 0 cm in line with the heels. Pressing the palms of the hands together and keeping the elbows fully extended, the participants shall bend their trunk as far as possible over the tape measure. The results will be expressed in centimeters reporting the distance left or passed from the feet.

Hamstring flexibility 3 months after the intervention will be measured using the V Sit and Reach test where the participant will be seated on the floor with knees fully extended and feet 30 cm apart. A tape measure will be placed on the floor, equidistant between the feet, placing the 0 cm in line with the heels. Pressing the palms of the hands together and keeping the elbows fully extended, the participants shall bend their trunk as far as possible over the tape measure. The results will be expressed in centimeters reporting the distance left or passed from the feet.

Hamstring flexibility 6 months after the intervention will be measured using the V Sit and Reach test where the participant will be seated on the floor with knees fully extended and feet 30 cm apart. A tape measure will be placed on the floor, equidistant between the feet, placing the 0 cm in line with the heels. Pressing the palms of the hands together and keeping the elbows fully extended, the participants shall bend their trunk as far as possible over the tape measure. The results will be expressed in centimeters reporting the distance left or passed from the feet.

Psychological variables will be assessed employing self-administered questionnaires specifically validated for cancer patients. Health-related quality of life will be assessed using the EORTC QLQ-C30 Quality of Life Questionnaire which includes functional and cancer-specific symptom assessment. Higher global scores will mean a higher quality of life.

Psychological variables will be assessed utilizing self-administered questionnaires specifically validated for cancer patients. Health-related quality of life will be assessed 3 months after the intervention using the EORTC QLQ-C30 Quality of Life Questionnaire which includes functional and cancer-specific symptom assessment. Higher global scores will mean a higher quality of life.

Psychological variables will be assessed through self-administered questionnaires specifically validated for cancer patients. Health-related quality of life 6 months after the intervention will be assessed using the EORTC QLQ-C30 Quality of Life Questionnaire which includes functional and cancer-specific symptom assessment. Higher global scores will mean a higher quality of life.

To assess cancer-related fatigue, the FACT-F questionnaire will be employed. It includes 13 items where patients will select their fatigue perception with a Likert scale from 1 to 5 being 1 the lowest fatigue score and 5 the highest.

To assess cancer-related fatigue after the intervention, the FACT-F questionnaire will be employed. It includes 13 items where patients will select their fatigue perception with a Likert scale from 1 to 5 being 1 the lowest fatigue score and 5 the highest.

To assess cancer-related fatigue 3 months after the intervention, the FACT-F questionnaire will be employed. It includes 13 items where patients will select their fatigue perception with a Likert scale from 1 to 5 being 1 the lowest fatigue score and 5 the highest.

To assess cancer-related fatigue 6 months after the intervention, the FACT-F questionnaire will be employed. It includes 13 items where patients will select their fatigue perception with a Likert scale from 1 to 5 being 1 the lowest fatigue score and 5 the highest.

Life satisfaction will be assessed using the Satisfaction With Life Scale (SWLS) questionnaire. The scale is composed of 5 items to score with a Likert scale from 1 (strongly disagree) to 5 (strongly agree).

Life satisfaction after the intervention will be assessed using the Satisfaction With Life Scale (SWLS) questionnaire. The scale is composed of 5 items to score with a Likert scale from 1 (strongly disagree) to 5 (strongly agree).

Life satisfaction 3 months after the intervention will be assessed using the Satisfaction With Life Scale (SWLS) questionnaire. The scale is composed of 5 items to score with a Likert scale from 1 (strongly disagree) to 5 (strongly agree).

Life satisfaction 6 months after the intervention will be assessed using the Satisfaction With Life Scale (SWLS) questionnaire. The scale is composed of 5 items to score with a Likert scale from 1 (strongly disagree) to 5 (strongly agree).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Ivabradine in the Management of Cardiac Autonomic Dysfunction Associated With Thoracic Radiation Therapy.	NCT03137537	Lymphoma Autonomic Imbal... Cancer Survivor...	Ivabradine Placebo Oral Ta...	18 Years - 80 Years	Dana-Farber Cancer Institute
Exercise Prescription Guided by Heart Rate Variability in Breast Cancer Patients	NCT05040867	Breast Cancer Cardiotoxicity Autonomic Imbal...	Physical exerci...	18 Years - 65 Years	GO fit Lab- Ingesport

Spots Global Cancer Trial Database for autonomic imbalance