Effects of Aerobic Training and Inspiratory Muscle Training in Patients During Hematopoietic Stem Cell Transplantation

Study Overview
=================
Brief Summary
-----------------
The hospitalization for hematopoietic stem cell transplantation (HSCT) impairs the physical functioning and functional capacity, but aerobic physical training and, more recently, inspiratory muscle training, have shown benefits to patients' health submitted to this intervention. However, is not known the effect of aerobic physical training combined with inspiratory muscle training in hospitalized patients for HSCT. The purpose of the study will be verify the safety, feasibility and effects of the training association.

Detailed Description
-----------------
Sample Patients consecutively admitted to Bone Marrow Transplantation Unit - University Hospital of Juiz de Fora - EBSERH will be included. Patients will be monitored from admission to hospital discharge and randomized by drawing on opaque paper for the Combined Physical Training Group (aerobic physical training + inspiratory muscle training) or the Aerobic Physical Training Group. Interview Volunteers will go through an interview and directed physical examination. All volunteers will respond to Baecke's questionnaire to investigate habitual physical activity levels. Feasibility and safety assessment of the study The viability of the study will be verified by: 1) recruitment (recruitment of at least 60% of eligible patients); 2) adherence (achievement of at least 70% of the total number of minutes of the scheduled interventions); 3) friction (percentage of patients who started but did not complete the intervention). Safety will be verified by the number of spontaneous or unexpected reactions and adverse events resulting from the proposed interventions. Quality of life and fatigue questionnaire To evaluate the quality of life, the European Organization for Research and Treatment of Cancer (EORTC-Quality of Life Questionnaire-C30) will be used. The fatigue will be evaluated by the Functional Assessment of Cancer Therapy - Fatigue (FACT-F) questionnaire, validated for the Portuguese language in Brazilian cancer patients. Anthropometric evaluation Height and body weight will be measured and the BMI calculated. Evaluation of hematological variables, clinical symptoms, duration of neutropenia and duration of hospital stay Data on hematological variables, the presence of clinical symptoms (diarrhea, constipation, nausea, vomiting, pain and fatigue), duration of neutropenia, need for infusion of red blood cells and platelets, and length of hospital stay in patients' files will be collected and collected. Evaluation of peripheral muscle strength In order to estimate the muscular strength of lower limbs (LIIII), the sit and stand test will be used for one minute. For the assessment of upper limb muscle strength, the mean value of three maximal hand grip exercises with the dominant limb will be calculated by means of the Jamar® upper limb dynamometer. Assessment of respiratory muscle strength The maximal inspiratory and expiratory pressures will be measured by digital manovacuometry (MVD300®). Evaluation of functional capacity The six-minute step test is a simplified functional capacity assessment procedure, often used in the clinical setting because of its ease of execution in the hospital setting. Also, to evaluate the functionality will be applied the Time Up and Go Test. Assessment of blood pressure and heart rate The oscillometric method will be applied, using the DIXTAL2023® device, which automatically assessing blood pressure. The heart rate will be evaluated continuously by standard derivation of the electrocardiogram cable of the DIXTAL 2023® multiparameter monitor and by the Polar® cardiac frequency meter (model RS800cx). Evaluation of cardiac autonomic control Cardiac autonomic control will be evaluated by heart rate variability (HRV) analysis. Evaluation of the cardiac autonomic control profile during hospitalization for HSCT It will be assessed after recording the heart rate for 10 minutes on days of hospital: admission, end of chemotherapy, onset and end of neutropenia and on hospital discharge. Aerobic physical training protocol All patients admitted to the Bone Marrow Transplantation Unit will participate in the aerobic physical training protocol, as indicated by the Standard Operating Procedure of the Physiotherapy Sector of the Rehabilitation Unit, University Hospital of Juiz de Fora - EBSERH. The aerobic physical training protocol will be performed five times a week, once a day and planned as follows: 1) heating (5-10 minutes), consisting of coordination training and resistance exercises; 2) moderate intensity aerobic physical training (10-20 minutes) performed on a lower limb cycle ergometer; 3) Cooling (5-10 minutes), consisting of muscle stretching and breathing exercises. During the aerobic training, heart rate and peripheral oxygen saturation will be recorded every 2 minutes, as well as blood pressure and subjective effort scale (BORG modified) every 5 minutes. The training target zone will be calculated from 50% to 70% of the reserve heart rate. Inspiratory Muscle Training Protocol Patients will be familiar with the correct technique for inspiratory muscle training, using the Power Breathe® device, breathing through mouthpiece and nasal clip. Individuals will be instructed to maintain diaphragmatic breathing, respiratory rate between 15 and 20 irpm, during 20 minutes daily, five times a week. The protocol will be performed in the sitting position with an established load of 40% of maximal inspiratory pressure for the combined physical training group. Clinical safety criteria for contraindication or discontinuation of training protocol The criteria will be to increase the heart rate above 20% of the training target zone, initial systolic blood pressure less than 90 or greater than 160mmHg, blood pressure greater than 170/100 mmHg during exercise, initial oxygen saturation less than 90% or desaturation (greater than 4% during exercise), body temperature greater than 38 °C, severe musculoskeletal pain, chest tightness, major dyspnea or tiredness (greater than 6 on the Borg Scale), dizziness, nausea, vomiting, epistaxis, or any active bleeding, loss or obstruction of the central or peripheral access catheter, loss or obstruction of the bladder catheter / nasogastric/enteral catheter and/or at the patient's request. Moreover, the hemoglobin (less than 7 mg/dl), hematocrit (less than 20%) and platelets (less than 10000 m3) will be absolute contraindications to perform protocols. Statistical treatment All volunteers included in the study will be evaluated statistically by intention-to-treat analysis. The data collected will first be submitted to exploratory analysis through boxplots, to verify measures of central tendency and dispersion, and to test data normality. From this preliminary investigation will be defined the statistical tests to be used.

Official Title
-----------------
Effects of Aerobic Training and Inspiratory Muscle Training in Patients During Hematopoietic Stem Cell Transplantation

Conditions
-----------------
Lymphoma, Myeloma, Leukemia, Aplastic Anemia

Intervention / Treatment
-----------------
* Other: Inspiratory Muscle Training
* Other: Aerobic Training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients consecutively admitted to Bone Marrow Transplantation-HU-UFJF-EBSERH for allogeneic or autologous HSCT Non-smokers Non-alcoholics Sedentary for at least three months prior to hospitalization Absence of orthopedic limitations and / or cognitive alterations that impede the physical training and the understanding of the evaluation instruments Exclusion Criteria: Patients hospitalized for post-HSCT complications or for other reasons that do not involve HSCT Patients who develop metastases and graft-versus-host disease during hospitalization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled clinical trial, with only statistical analysis blinded
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aerobic Physical Training<br>Aerobic Training | Other: Aerobic Training<br>* The aerobic physical training will be perform using a cycle ergometer, during 20 minutes daily, five times a week, with moderate intensity (50-70% of reserve heart rate).<br>|
| Experimental: Combined Physical Training<br>Inspiratory Muscle Training Aerobic Training | Other: Inspiratory Muscle Training<br>* The Inspiratory Muscle Training will be perform using using the Power Breathe® device, during 20 minutes daily, five times a week. The protocol will be performed in the sitting position with an established load of 40% of maximal inspiratory pressure.<br>Other: Aerobic Training<br>* The aerobic physical training will be perform using a cycle ergometer, during 20 minutes daily, five times a week, with moderate intensity (50-70% of reserve heart rate).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal Inspiratory Pressure Test | The maximal inspiratory pressure will be measured by digital manovacuometry (cmH20) | On the admission and hospital discharge, an average of 20 to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Aerobic and Inspiratory Muscle Training | The feasibility of the study will be verified by recruitment (%), adherence (%) and friction (%). | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Incidence of Aerobic and Inspiratory Muscle Training - Adverse Events (Safety) | Safety will be verified by the number of spontaneous or unexpected reactions and adverse events resulting from the proposed interventions. | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Quality of Life | To evaluate the quality of life, the European Organization for Research and Treatment of Cancer (EORTC-QLQ-C30) will be used. It will be considered the score of the global health, functional health and symptoms domains. | On the admission and hospital discharge, an average of 20 to 30 days | 
| Fatigue | The fatigue will be evaluated by the total score of Functional Assessment of Cancer Therapy - Fatigue (FACT-F) questionnaire. | On the admission and hospital discharge, an average of 20 to 30 days | 
| Hematological Variables | Patient records will be consulted and collected daily in order to verify the white cells, red cells and platelets counts. | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Clinical Symptoms | Patient records will be consulted and collected daily in order to verify the presence of diarrhea, pain, nausea, vomiting, fever, hair loss, fatigue, shortness of breath. | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Duration of Neutropenia | Patient records will be consulted and collected daily in order to verify the number of the days in which the patient will be in neutropenia. | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Duration of Hospitalization | Patient records will be consulted and collected daily in order to verify the number of the days in which the patient will be hospitalized. | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Muscle Strength of Lower Limbs | The muscular strength of lower limbs (LIIII) will be verified by the sit and stand test will be used for one minute (number of repetitions). | On the admission and hospital discharge, an average of 20 to 30 days | 
| Muscle Strength of Upper Limbs | For the assessment of upper limb muscle strength will be used Jamar® upper limb dynamometer (kgf). | On the admission and hospital discharge, an average of 20 to 30 days | 
| Functional Capacity | The six-minute step test will be used and the number of up and down steps will be considered. | On the admission and hospital discharge, an average of 20 to 30 days | 
| Functionality | The Time Up and Go Test will be used and the time to execute the test will be considered in seconds (s). | On the admission and hospital discharge, an average of 20 to 30 days | 
| Blood Pressure | The oscillometric method will be applied, using the DIXTAL2023® device to evaluate the systolic, diastolic and mean blood pressure (mmHg). | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Heart Rate | The heart rate (beats per minute) will be evaluated continuously by standard derivation of the electrocardiogram cable of the DIXTAL 2023® multiparameter monitor and by the Polar® cardiac frequency meter (model RS800cx). | During the entire hospitalization, daily, during an average of 20 to 30 days | 
| Cardiac Autonomic Control | The cardiac autonomic control will be assessed by the frequency (ms2 and nu) and time domains (ms) of heart rate variability analysis. | Hospital admission day, the end of chemotherapy day, the beginning and end of neutropenia days and the day of hospital discharge, during an average of 20 to 30 days to study completion. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aerobic Exercise, Hematopoietic Stem Cell Transplantation, Breathing Exercises, Inspiratory Capacity, Muscle Strength, Exercise Tolerance, Autonomic Nervous System