<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03028168</url>
  </required_header>
  <id_info>
    <org_study_id>110069</org_study_id>
    <nct_id>NCT03028168</nct_id>
  </id_info>
  <brief_title>Yôga and Breathing Techniques Training in Patients With Heart Failure and Preserved Ejection Fraction</brief_title>
  <official_title>Yôga and Breathing Techniques Training in Patients With Heart Failure and Preserved Ejection Fraction: Study Protocol for a Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Current therapies for heart failure (HF) bring together strategies to improve quality of life&#xD;
      and exercise tolerance, as well as to reduce morbidity and mortality. Some HF patients&#xD;
      present changes in the musculoskeletal system and inspiratory muscle weakness, which may be&#xD;
      restored by inspiratory muscle training, thus increasing respiratory muscle strength and&#xD;
      endurance, maximum oxygen consumption (VO2), functional capacity, respiratory responses to&#xD;
      exercise, and quality of life. Yoga therapies have been shown to improve quality of life,&#xD;
      inflammatory markers, and VO2 peak in HF patients, mostly with reduced ejection fraction&#xD;
      (HFrEF). However, the effect of different yoga breathing techniques in patients with HF with&#xD;
      preserved ejection fraction (HFpEF) has yet to be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Yôga techniques without breathing control have shown to improve oxygen consumption in&#xD;
      patients with HF, mostly HFrEF. However, almost half of HF patients present with HFpEF, and&#xD;
      less studies have been performed in those patients. It has been recently demonstrated that&#xD;
      HFpEF induces significant molecular, mitochondrial, histological, and functional alterations&#xD;
      in the diaphragm and soleus, which were attenuated by exercise training . In cardiac disease&#xD;
      and aging, several authors have shown a significant reduction in heart rate variability (HRV)&#xD;
      in the frequency ranges associated with breathing, by using spectral analysis of heart rate&#xD;
      (HR) and respiration.Therefore, the present randomized clinical trial (RCT) will be conducted&#xD;
      in order to test the hypothesis that an program of yôga and specific breathing techniques&#xD;
      with different ventilatory rhythms could be associated with improvement in inspiratory muscle&#xD;
      responses, functional capacity, oxygen uptake efficiency slope (OUES), circulatory power,&#xD;
      oscillatory ventilation, kinetics of oxygen consumption in the recovery period, distinct&#xD;
      features of the autonomic nervous system, natriuretic peptides, echocardiographic&#xD;
      measurements, and quality of life (QoL) in patients with HFpEF, with and without inspiratory&#xD;
      muscle weakness (IMW).Therefore, the present randomized clinical trial (RCT) will be&#xD;
      conducted in order to test the hypothesis that an 8-week program of yôga and specific&#xD;
      breathing techniques with different ventilatory rhythms could be associated with improvement&#xD;
      in inspiratory muscle responses, functional capacity, oxygen uptake efficiency slope (OUES),&#xD;
      circulatory power, oscillatory ventilation, kinetics of oxygen consumption in the recovery&#xD;
      period, distinct features of the autonomic nervous system, natriuretic peptides,&#xD;
      echocardiographic measurements, and quality of life in patients with HFpEF, with and without&#xD;
      IMW.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2012</start_date>
  <completion_date type="Actual">August 2017</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Health Services Research</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal inspiratory pressure (PImax)</measure>
    <time_frame>up to 8 weeks</time_frame>
    <description>Inspiratory muscle strength by measuring maximal inspiratory pressure (PImax)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak oxygen uptake (peak VO2)</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Peak VO2 will be considered the highest value of VO2 calculated in a 20-second-period during cardiopulmonary exercise testing (CPET)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vagal activity: heart rate variability- HRV</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Twenty-four-hour ECG recordings will be obtained with a light digital recorder for to available of heart rate variability (HRV).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional capacity through the 6-minute walk test (6MWD)</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>The maximum distance walked in 6 minutes of walking (6MWD).The distance traveled in the time of 6 minutes will be considered according to the predicted for gender and age of the patient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life Minnesota scores</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Quality of life Minnesota scores as a specific inventory for patients with Heart Failure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>N-terminal pro-brain natriuretic (NT-proBNP)</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>NT-proBNP test: N-terminal precursor of natriuretic peptide type B (Brain), clinical specimen by serum, sandwich-type electrochemiluminescence analysis method (COBAS E601-ROCHE).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Echocardiographic - Ejection Fraction</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Teichholz method: ejection fraction - study Inclusion criteria: EF≥ 50% . Establish a diagnostic measure of HF by confirming preserved ejection fraction and compare this measure at the end of the study.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Other pulmonary functions - Inspiratory muscle force</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Additionally, for the determination of inspiratory muscle force, an incremental test will be used in which patients will breathe continuously through a mouthpiece connected to a measure device. The patients will use an initial load of 50% of PImax, and increments of 10% of PImax will be added every 3 min until the patient is unable to continue breathing.</description>
  </other_outcome>
  <other_outcome>
    <measure>Oher pulmonary functions - Inspiratory muscle endurance</measure>
    <time_frame>Baseline and 8 weeks</time_frame>
    <description>Additionally, for the determination of inspiratory muscle endurance, an incremental test will be used in which patients will breathe continuously through a mouthpiece connected to a measure device. The protocol, subjects will breathe against a constant inspiratory submaximal load equivalent to 80% of the greatest inspiratory pressure and the time elapsed to task failure will be defined as the inspiratory endurance time.</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Cardiovascular Diseases</condition>
  <condition>Heart Failure</condition>
  <condition>Heart Failure, Diastolic</condition>
  <arm_group>
    <arm_group_label>Intervention Yôga</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active protocol with yôga body movements performed along with respiratory vigorous, without contentions. Two sessions per week, with 45 minutes duration.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intervention breathing technique</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Passive protocol, seated patient, no significant body movements. Breathing technique, with alternate nostril breathing combined to inspiratory and expiratory retentions.Two sessions per week, with 45 minutes duration</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Control group (standard pharmacological treatment). Patients will be oriented to keep their pharmacological routine and daily activities, with no structured exercises. They will have to return to the hospital for post-testing after 8 weeks from randomization.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Yôga</intervention_name>
    <description>Intervention observing respiratory frequency (RF) of 15- 20 respiratory cycles per minute (rcpm). A standardized 7-minute final relaxation .</description>
    <arm_group_label>Intervention Yôga</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Breathing technique</intervention_name>
    <description>Intervention uses diaphragmatic breathing, observing slow respiratory frequency, between 5-8 rcpm. A standardized 7-minute final relaxation.</description>
    <arm_group_label>Intervention breathing technique</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control group</intervention_name>
    <description>Patients will be oriented to keep their pharmacological routine and daily activities, with no structured exercises. They will have to return to the hospital for post-testing after 8 weeks from randomization</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult patients with a diagnosis of HFpEF, functional capacity class II and III, who&#xD;
             are being treated at a specialized HF clinic will be eligible. HF diagnosis will be&#xD;
             established by clinical history (signs and symptoms), echocardiographic findings (left&#xD;
             ventricular ejection fraction ≥ 50%) and medical records confirming management for HF.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pulmonary disease (forced vital capacity&lt;80% of predicted and/or forced expiratory&#xD;
             volume in 1 s &lt;70% of predicted, significant mitral or aortic valve diseases, history&#xD;
             of exercise-induced asthma, and active smoking or alcoholic.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andréia Biolo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Clinicas de Porto Alegre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital ULBRA - Mãe de Deus</name>
      <address>
        <city>Canoas</city>
        <state>Rio Grande Do Sul</state>
        <zip>92425900</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90035903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 23, 2017</study_first_posted>
  <last_update_submitted>February 22, 2018</last_update_submitted>
  <last_update_submitted_qc>February 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Yôga</keyword>
  <keyword>Breathing Techniques</keyword>
  <keyword>Heart Failure and Preserved Ejection Fraction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Heart Failure, Diastolic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03028168
org study id: 110069
nct id: NCT03028168
lead sponsor: 
has dmc: No
Current therapies for heart failure (HF) bring together strategies to improve quality of life
      and exercise tolerance, as well as to reduce morbidity and mortality. Some HF patients
      present changes in the musculoskeletal system and inspiratory muscle weakness, which may be
      restored by inspiratory muscle training, thus increasing respiratory muscle strength and
      endurance, maximum oxygen consumption (VO2), functional capacity, respiratory responses to
      exercise, and quality of life. Yoga therapies have been shown to improve quality of life,
      inflammatory markers, and VO2 peak in HF patients, mostly with reduced ejection fraction
      (HFrEF). However, the effect of different yoga breathing techniques in patients with HF with
      preserved ejection fraction (HFpEF) has yet to be assessed.
Yôga techniques without breathing control have shown to improve oxygen consumption in
      patients with HF, mostly HFrEF. However, almost half of HF patients present with HFpEF, and
      less studies have been performed in those patients. It has been recently demonstrated that
      HFpEF induces significant molecular, mitochondrial, histological, and functional alterations
      in the diaphragm and soleus, which were attenuated by exercise training . In cardiac disease
      and aging, several authors have shown a significant reduction in heart rate variability (HRV)
      in the frequency ranges associated with breathing, by using spectral analysis of heart rate
      (HR) and respiration.Therefore, the present randomized clinical trial (RCT) will be conducted
      in order to test the hypothesis that an program of yôga and specific breathing techniques
      with different ventilatory rhythms could be associated with improvement in inspiratory muscle
      responses, functional capacity, oxygen uptake efficiency slope (OUES), circulatory power,
      oscillatory ventilation, kinetics of oxygen consumption in the recovery period, distinct
      features of the autonomic nervous system, natriuretic peptides, echocardiographic
      measurements, and quality of life (QoL) in patients with HFpEF, with and without inspiratory
      muscle weakness (IMW).Therefore, the present randomized clinical trial (RCT) will be
      conducted in order to test the hypothesis that an 8-week program of yôga and specific
      breathing techniques with different ventilatory rhythms could be associated with improvement
      in inspiratory muscle responses, functional capacity, oxygen uptake efficiency slope (OUES),
      circulatory power, oscillatory ventilation, kinetics of oxygen consumption in the recovery
      period, distinct features of the autonomic nervous system, natriuretic peptides,
      echocardiographic measurements, and quality of life in patients with HFpEF, with and without
      IMW.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Health Services Research
masking: Single (Outcomes Assessor)
measure: Maximal inspiratory pressure (PImax)
time frame: up to 8 weeks
description: Inspiratory muscle strength by measuring maximal inspiratory pressure (PImax)
measure: Peak oxygen uptake (peak VO2)
time frame: Baseline and 8 weeks
description: Peak VO2 will be considered the highest value of VO2 calculated in a 20-second-period during cardiopulmonary exercise testing (CPET)
measure: Vagal activity: heart rate variability- HRV
time frame: Baseline and 8 weeks
description: Twenty-four-hour ECG recordings will be obtained with a light digital recorder for to available of heart rate variability (HRV).
measure: Functional capacity through the 6-minute walk test (6MWD)
time frame: Baseline and 8 weeks
description: The maximum distance walked in 6 minutes of walking (6MWD).The distance traveled in the time of 6 minutes will be considered according to the predicted for gender and age of the patient.
measure: Quality of life Minnesota scores
time frame: Baseline and 8 weeks
description: Quality of life Minnesota scores as a specific inventory for patients with Heart Failure.
measure: N-terminal pro-brain natriuretic (NT-proBNP)
time frame: Baseline and 8 weeks
description: NT-proBNP test: N-terminal precursor of natriuretic peptide type B (Brain), clinical specimen by serum, sandwich-type electrochemiluminescence analysis method (COBAS E601-ROCHE).
measure: Echocardiographic - Ejection Fraction
time frame: Baseline and 8 weeks
description: Teichholz method: ejection fraction - study Inclusion criteria: EF≥ 50% . Establish a diagnostic measure of HF by confirming preserved ejection fraction and compare this measure at the end of the study.
measure: Other pulmonary functions - Inspiratory muscle force
time frame: Baseline and 8 weeks
description: Additionally, for the determination of inspiratory muscle force, an incremental test will be used in which patients will breathe continuously through a mouthpiece connected to a measure device. The patients will use an initial load of 50% of PImax, and increments of 10% of PImax will be added every 3 min until the patient is unable to continue breathing.
measure: Oher pulmonary functions - Inspiratory muscle endurance
time frame: Baseline and 8 weeks
description: Additionally, for the determination of inspiratory muscle endurance, an incremental test will be used in which patients will breathe continuously through a mouthpiece connected to a measure device. The protocol, subjects will breathe against a constant inspiratory submaximal load equivalent to 80% of the greatest inspiratory pressure and the time elapsed to task failure will be defined as the inspiratory endurance time.
arm group label: Intervention Yôga
arm group type: Experimental
description: Active protocol with yôga body movements performed along with respiratory vigorous, without contentions. Two sessions per week, with 45 minutes duration.
arm group label: Intervention breathing technique
arm group type: Experimental
description: Passive protocol, seated patient, no significant body movements. Breathing technique, with alternate nostril breathing combined to inspiratory and expiratory retentions.Two sessions per week, with 45 minutes duration
arm group label: Control group
arm group type: Experimental
description: Control group (standard pharmacological treatment). Patients will be oriented to keep their pharmacological routine and daily activities, with no structured exercises. They will have to return to the hospital for post-testing after 8 weeks from randomization.
intervention type: Other
intervention name: Yôga
description: Intervention observing respiratory frequency (RF) of 15- 20 respiratory cycles per minute (rcpm). A standardized 7-minute final relaxation .
arm group label: Intervention Yôga
intervention type: Other
intervention name: Breathing technique
description: Intervention uses diaphragmatic breathing, observing slow respiratory frequency, between 5-8 rcpm. A standardized 7-minute final relaxation.
arm group label: Intervention breathing technique
intervention type: Other
intervention name: Control group
description: Patients will be oriented to keep their pharmacological routine and daily activities, with no structured exercises. They will have to return to the hospital for post-testing after 8 weeks from randomization
arm group label: Control group
criteria: 
gender: All
minimum age: 45 Years
maximum age: 75 Years
healthy volunteers: No
last name: Andréia Biolo, MD
role: Principal Investigator
affiliation: Hospital de Clinicas de Porto Alegre
facility: 
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Heart Failure
mesh term: Cardiovascular Diseases
mesh term: Heart Failure, Diastolic
sharing ipd: Undecided