<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/NCT03775577</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00129787</org_study_id>
    <secondary_id>R01HL061912</secondary_id>
    <nct_id>NCT03775577</nct_id>
  </id_info>
  <brief_title>Exercise Intolerance in Heart Failure</brief_title>
  <official_title>Exercise Intolerance in Heart Failure: the Role of Altered Cardiac and Skeletal Muscle Energetics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators are studying whether metabolic abnormalities in cardiac and skeletal muscle&#xD;
      in patients with heart failure with preserved ejection fraction (HFpEF) are associated with&#xD;
      debilitating exercise intolerance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research is being done to better understand why patients with heart failure have&#xD;
      difficulty exercising and performing some activities of daily living. Heart muscle and&#xD;
      skeletal muscle (in the legs and arms) depend on normal metabolism (the conversion of foods&#xD;
      to chemical fuel) to function properly. Investigators will measure metabolites in the heart&#xD;
      and leg muscles, including the levels of high energy phosphates and lipids (fats) using&#xD;
      magnetic resonance (MR) techniques. High-energy phosphates serve as a source of energy, which&#xD;
      is used by the heart and skeletal muscle for contraction. Magnetic resonance uses magnetic&#xD;
      fields to measure the levels of these substances.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 1, 2017</start_date>
  <completion_date type="Anticipated">March 2025</completion_date>
  <primary_completion_date type="Anticipated">March 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Skeletal muscle mitochondrial function</measure>
    <time_frame>Baseline</time_frame>
    <description>Maximal oxidative capacity of leg muscle measured by 31P Magnetic Resonance Spectroscopy (MRS)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Skeletal muscle energetic decline during exercise</measure>
    <time_frame>Baseline</time_frame>
    <description>Creatine phosphate rate of decline (umol/g/min) during plantar flexion exercise measured by 31P MRS</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiac muscle energetics</measure>
    <time_frame>Baseline</time_frame>
    <description>Cardiac muscle phosphocreatine (PCr)/ adenosine triphosphate (ATP) and creatine kinase(CK) flux (umol/g/s) measured by 31P MRS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Six minute walk test</measure>
    <time_frame>Six months</time_frame>
    <description>Six minute walk distance (m)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiopulmonary exercise testing (CPET)</measure>
    <time_frame>Six months</time_frame>
    <description>Peak whole-body oxygen consumption rate during exercise</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical heart failure outcome as assessed by number of hospitalizations</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical heart failure outcome as assessed by time to cardiovascular death</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical heart failure outcome as assessed by overall mortality</measure>
    <time_frame>Two years</time_frame>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Heart Failure With Normal Ejection Fraction</condition>
  <arm_group>
    <arm_group_label>HFpEF</arm_group_label>
    <description>Participants with Heart Failure with Preserved Ejection Fraction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HFrEF</arm_group_label>
    <description>Participants with Heart Failure with Reduced Ejection Fraction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hypertensive Subjects</arm_group_label>
    <description>Participants with Hypertension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Subjects</arm_group_label>
    <description>Participants without heart failure and without commodities</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood Specimens&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        People with and without heart failure will be enrolled.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients of either gender who are greater than 21 years of age (no upper age limit),&#xD;
&#xD;
          -  Permission of patient's clinical attending physician,&#xD;
&#xD;
          -  Previous clinical diagnosis of HF with current New York Heart Association (NYHA) Class&#xD;
             II-III symptoms for at least 1 month,&#xD;
&#xD;
          -  Left ventricular ejection fraction (EF) &gt;50% by echocardiography, MRI, CT or x-ray or&#xD;
             nuclear ventriculography within prior 12 months,&#xD;
&#xD;
          -  Stable medical therapy for at least 30 days (no addition or removal or major (&gt;100%)&#xD;
             dose change of Renin-Angiotensin-Aldosterone System (RAAS) antagonists, beta-blockers,&#xD;
             or calcium channel blockers for hypertension).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to understand the risks, benefits, and alternatives of participation and give&#xD;
             meaningful consent,&#xD;
&#xD;
          -  Contraindications to MRI such as implanted metallic objects (pre-existing cardiac&#xD;
             pacemakers, cerebral clips) or indwelling metallic projectiles,&#xD;
&#xD;
          -  Significant valvular abnormalities,&#xD;
&#xD;
          -  Pregnant women (women of childbearing potential will undergo blood or urine pregnancy&#xD;
             testing),&#xD;
&#xD;
          -  History of clinical CAD or significant epicardial coronary disease (&gt;50% stenosis) in&#xD;
             major coronary artery by x-ray or CT angiography unless (a) the patient underwent&#xD;
             prior successful revascularization with percutaneous coronary angioplasty within the&#xD;
             prior three years and (b) there are no residual lesions of &gt;50% on the most recent&#xD;
             coronary angiographic study.&#xD;
&#xD;
          -  History of infiltrative cardiomyopathy or constrictive pericarditis,&#xD;
&#xD;
          -  Cor pulmonale,&#xD;
&#xD;
          -  Significant pulmonary disease,&#xD;
&#xD;
          -  Estimated glomerular filtration rate (eGFR) &lt;20ml/min,&#xD;
&#xD;
          -  Any condition other than HF which could limit the ability to perform a 6MW or&#xD;
             cardiopulmonary exercise test (CPET) test (e.g., critical peripheral vascular disease,&#xD;
             significant orthopedic or neurological conditions),&#xD;
&#xD;
          -  Any diseases other than HF which are likely to significantly alter the patient's&#xD;
             global perception of status or quality of life over a period of 6 months.&#xD;
&#xD;
          -  Significant peripheral vascular disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Robert G Weiss, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Matthew Kauffman</last_name>
    <phone>443-287-3475</phone>
    <email>mkauffm7@jhmi.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tricia Steinberg, RN, MSN</last_name>
    <phone>443-287-3469</phone>
    <email>asteinb3@jhmi.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tricia Steinberg, MSN</last_name>
      <phone>443-287-3469</phone>
      <email>asteinb3@jhmi.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>November 1, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Failure with Preserved Ejection Fraction</keyword>
  <keyword>HFpEF</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03775577
org study id: IRB00129787
secondary id: R01HL061912
nct id: NCT03775577
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The investigators are studying whether metabolic abnormalities in cardiac and skeletal muscle
      in patients with heart failure with preserved ejection fraction (HFpEF) are associated with
      debilitating exercise intolerance.
This research is being done to better understand why patients with heart failure have
      difficulty exercising and performing some activities of daily living. Heart muscle and
      skeletal muscle (in the legs and arms) depend on normal metabolism (the conversion of foods
      to chemical fuel) to function properly. Investigators will measure metabolites in the heart
      and leg muscles, including the levels of high energy phosphates and lipids (fats) using
      magnetic resonance (MR) techniques. High-energy phosphates serve as a source of energy, which
      is used by the heart and skeletal muscle for contraction. Magnetic resonance uses magnetic
      fields to measure the levels of these substances.
observational model: Cohort
time perspective: Prospective
measure: Skeletal muscle mitochondrial function
time frame: Baseline
description: Maximal oxidative capacity of leg muscle measured by 31P Magnetic Resonance Spectroscopy (MRS)
measure: Skeletal muscle energetic decline during exercise
time frame: Baseline
description: Creatine phosphate rate of decline (umol/g/min) during plantar flexion exercise measured by 31P MRS
measure: Cardiac muscle energetics
time frame: Baseline
description: Cardiac muscle phosphocreatine (PCr)/ adenosine triphosphate (ATP) and creatine kinase(CK) flux (umol/g/s) measured by 31P MRS
measure: Six minute walk test
time frame: Six months
description: Six minute walk distance (m)
measure: Cardiopulmonary exercise testing (CPET)
time frame: Six months
description: Peak whole-body oxygen consumption rate during exercise
measure: Clinical heart failure outcome as assessed by number of hospitalizations
time frame: Two years
measure: Clinical heart failure outcome as assessed by time to cardiovascular death
time frame: Two years
measure: Clinical heart failure outcome as assessed by overall mortality
time frame: Two years
arm group label: HFpEF
description: Participants with Heart Failure with Preserved Ejection Fraction
arm group label: HFrEF
description: Participants with Heart Failure with Reduced Ejection Fraction
arm group label: Hypertensive Subjects
description: Participants with Hypertension
arm group label: Healthy Subjects
description: Participants without heart failure and without commodities
Blood Specimens
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Robert G Weiss, MD
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Matthew Kauffman
phone: 443-287-3475
email: mkauffm7@jhmi.edu
last name: Tricia Steinberg, RN, MSN
phone: 443-287-3469
email: asteinb3@jhmi.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: No