<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/NCT03032081</url>
  </required_header>
  <id_info>
    <org_study_id>UL1TR000454</org_study_id>
    <secondary_id>CRN 00091835</secondary_id>
    <nct_id>NCT03032081</nct_id>
  </id_info>
  <brief_title>High Intensity Interval Training in Heart Failure</brief_title>
  <official_title>High Intensity Interval Training in Heart Failure: The Gold Standard of Future Patient Care</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Georgia State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Georgia State University</source>
  <oversight_info>
    <has_dmc>Yes</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 will assess the efficacy and safety of utilizing high-intensity interval&#xD;
      training in stable heart failure patients on functional outcomes. Specifically, an assessment&#xD;
      of baseline peak oxygen uptake and peak cardiac output will be assessed before and 8 weeks&#xD;
      after intense interval training. Measurements of quality of life will be assessed before and&#xD;
      after training as well as the number of arrhythmic events before and after training. The&#xD;
      control group will be a group that will follow a moderate exercise training protocol over a&#xD;
      similar period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Aerobic exercise training of moderate intensity is recommended as safe and effective for all&#xD;
      stable outpatients with chronic heart failure who are able to participate in improving&#xD;
      physical conditioning. Emerging data suggest that high-intensity exercise training in select&#xD;
      heart failure patients may achieve even greater improvement in functional capacity than&#xD;
      moderate intensity training leading to a better quality of life. In the few studies to date,&#xD;
      aerobic capacity, heart function is increased to a better extent in heart failure patients&#xD;
      that undergo an eight-week high-intensity exercise program (32 exercise sessions) compared to&#xD;
      the standard of care. The goal of this pilot study is to collect data on safety and efficacy&#xD;
      of high-intensity interval training in stable heart failure patients to demonstrate better&#xD;
      physiological and clinical outcomes with fewer long-term health care costs compared to the&#xD;
      standard of care. Twenty participants with stable heart failure (age range = 40 to 65 years&#xD;
      of age) will be randomized into two different groups: the standard of care group, in which&#xD;
      subjects will exercise for 40 minutes at 40 to 60 % of heart rate reserve (HRR) for eight&#xD;
      weeks (32 sessions); and the high-intensity interval training group, in which subjects will&#xD;
      perform four sets of 4-minutes at &gt; 85% of HRR, with three minutes of active rest between&#xD;
      intervals, for six weeks (32 sessions). The functional outcomes measured will be cardiac&#xD;
      function (i.e. stroke volume, cardiac output, ejection fraction), pulmonary function&#xD;
      (diffusing capacity, lung volumes, spirometry), exercise capacity (peak oxygen uptake) at&#xD;
      rest and during exercise before and after eight weeks of exercise training (32 sessions).&#xD;
      Adverse events related to each exercise training session (i.e. cardiac arrest, myocardial&#xD;
      infarction during exercise, or within the first hour afterward) as well as arrhythmias will&#xD;
      be recorded via Holter monitoring 24-hrs post-exercise. Quality of life will also be&#xD;
      measured. The exercise training will be supervised at Grady Hospital. This novel approach has&#xD;
      the chance to become impactful to these patients and will challenge the current negative&#xD;
      perception of high-intensity exercise training in this patient population. The investigators&#xD;
      anticipate this study will help reform the current exercise guidelines in these participants.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    PI relocated, unable to complete the study. No replacement PI identified.&#xD;
  </why_stopped>
  <start_date type="Actual">March 2, 2017</start_date>
  <completion_date type="Anticipated">July 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2018</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cardiac output</measure>
    <time_frame>8 weeks</time_frame>
    <description>Measures how much blood is ejected from the left ventricle of the heart per minute (L/min). We will look at this at rest and at peak exercise.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ejection fraction</measure>
    <time_frame>8 weeks</time_frame>
    <description>Measures the fraction of blood ejected from the left ventricle at every heart beat (%). We will look at this at rest and at peak exercise.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pulmonary diffusing capacity</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Measures gas transfer at the lung in mL/min/mmHg. We will look at this at rest and at peak exercise.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Global longitudinal strain</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Measures measuring regional or global deformation of the heart measure in (number/s) at rest.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability</measure>
    <time_frame>8 weeks</time_frame>
    <description>A measurement of either increased sympathetic or reduced vagal activity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of arrhythmic events</measure>
    <time_frame>over a 24 hr period, before 8 weeks of training and after 8 weeks of training</time_frame>
    <description>We are examining the number of times there is a recorded irregularity in the force or rhythm of the heartbeat.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>8 weeks</time_frame>
    <description>The MacNew Quality of Life questionnaire will be used to assess the emotional, physical, and social domains</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Heart Failure</condition>
  <condition>Physical Activity</condition>
  <arm_group>
    <arm_group_label>High Intensity Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 set of 4 minutes of cycling intense exercise, 4 days per week, for 8 weeks at about 80% to 90% of heart rate reserve</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Moderate Intensity Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>40 to 47 minutes of continuous cycling exercise at 50% to 60% of heart rate reserve, 4 days per week, for 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>High intensity exercise</intervention_name>
    <description>High intensity exercise, defined as an exercise intensity of &gt; 80% of heart rate reserve. Heart rate reserve is the maximum measured heart rate minus the measured resting heart rate.</description>
    <arm_group_label>High Intensity Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Moderate intensity exercise</intervention_name>
    <description>Moderate intensity exercise, defined as 50 to 60% of heart rate reserve for 40 to 47 minutes per day, 4 days per week, for 8 weeks. Heart rate reserve is the maximum measured heart rate minus the measured resting heart rate.</description>
    <arm_group_label>Moderate Intensity Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Stable, chronic heart failure with a left ventricular ejection fraction of 20 to 40%.&#xD;
&#xD;
          2. New York Heart Association (NYHA) class I to III symptoms with treatment that includes&#xD;
             beta-blocker and angiotensin-converting enzyme (ACE) inhibitor and angiotensin&#xD;
             receptor blocker (ARB) Therapy for at least eight weeks prior to exercise training if&#xD;
             ejection fraction is &lt; 35%.&#xD;
&#xD;
          3. No recent major cardiovascular hospitalizations or procedures within the previous&#xD;
             three months.&#xD;
&#xD;
          4. Age 40-65 years&#xD;
&#xD;
          5. Aerobic capacity ≥ 12 mL/kg/min.&#xD;
&#xD;
          6. Subjects with an implantable cardioverter defibrillator (ICD) are also included.&#xD;
&#xD;
          7. Subjects with right ventricular systolic pressure ≤ 60 mmHg at rest.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to exercise (orthopedic or neurological problems).&#xD;
&#xD;
          2. History of seizure disorders.&#xD;
&#xD;
          3. History of atrial fibrillation or ventricular tachycardia in the past 3 months.&#xD;
&#xD;
          4. Implantable cardioverter defibrillator shocks due to atrial fibrillation or&#xD;
             ventricular fibrillation within the past 3 months.&#xD;
&#xD;
          5. Presence of pacemaker.&#xD;
&#xD;
          6. Uncontrolled diabetes mellitus.&#xD;
&#xD;
          7. Diabetic insulin pump.&#xD;
&#xD;
          8. Uncontrolled hypertension.&#xD;
&#xD;
          9. Renal insufficiency (creatinine: &gt; 2.5 mg/dl).&#xD;
&#xD;
         10. Severe left ventricular hypertrophy (&gt; 1.8 cm wall thickness) or dynamic left&#xD;
             ventricular outflow tract obstruction.&#xD;
&#xD;
         11. Greater than mild degree of valve stenosis or presence of an artificial heart valve.&#xD;
&#xD;
         12. Drug addiction.&#xD;
&#xD;
         13. Not being able to read and understand the consent form.&#xD;
&#xD;
         14. Signs of unreliableness.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gerald S Zavorsky, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgia State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Grady Memorial Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007 Jun 19;115(24):3086-94. doi: 10.1161/CIRCULATIONAHA.106.675041. Epub 2007 Jun 4.</citation>
    <PMID>17548726</PMID>
  </reference>
  <reference>
    <citation>Meyer P, Gayda M, Juneau M, Nigam A. High-intensity aerobic interval exercise in chronic heart failure. Curr Heart Fail Rep. 2013 Jun;10(2):130-8. doi: 10.1007/s11897-013-0130-3.</citation>
    <PMID>23397179</PMID>
  </reference>
  <reference>
    <citation>Flynn KE, Pina IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ, Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman KA, Spertus JA, O'Connor CM, Weinfurt KP; HF-ACTION Investigators. Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1451-9. doi: 10.1001/jama.2009.457. Erratum In: JAMA. 2009 Dec 2;302(21):2322.</citation>
    <PMID>19351942</PMID>
  </reference>
  <reference>
    <citation>Guiraud T, Labrunee M, Gaucher-Cazalis K, Despas F, Meyer P, Bosquet L, Gales C, Vaccaro A, Bousquet M, Galinier M, Senard JM, Pathak A. High-intensity interval exercise improves vagal tone and decreases arrhythmias in chronic heart failure. Med Sci Sports Exerc. 2013 Oct;45(10):1861-7. doi: 10.1249/MSS.0b013e3182967559.</citation>
    <PMID>23591293</PMID>
  </reference>
  <reference>
    <citation>Freyssin C, Verkindt C, Prieur F, Benaich P, Maunier S, Blanc P. Cardiac rehabilitation in chronic heart failure: effect of an 8-week, high-intensity interval training versus continuous training. Arch Phys Med Rehabil. 2012 Aug;93(8):1359-64. doi: 10.1016/j.apmr.2012.03.007. Epub 2012 Mar 21.</citation>
    <PMID>22446291</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>January 24, 2017</study_first_submitted>
  <study_first_submitted_qc>January 24, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>August 21, 2017</last_update_submitted>
  <last_update_submitted_qc>August 21, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>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/NCT03032081
org study id: UL1TR000454
secondary id: CRN 00091835
nct id: NCT03032081
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The investigators will assess the efficacy and safety of utilizing high-intensity interval
      training in stable heart failure patients on functional outcomes. Specifically, an assessment
      of baseline peak oxygen uptake and peak cardiac output will be assessed before and 8 weeks
      after intense interval training. Measurements of quality of life will be assessed before and
      after training as well as the number of arrhythmic events before and after training. The
      control group will be a group that will follow a moderate exercise training protocol over a
      similar period.
Aerobic exercise training of moderate intensity is recommended as safe and effective for all
      stable outpatients with chronic heart failure who are able to participate in improving
      physical conditioning. Emerging data suggest that high-intensity exercise training in select
      heart failure patients may achieve even greater improvement in functional capacity than
      moderate intensity training leading to a better quality of life. In the few studies to date,
      aerobic capacity, heart function is increased to a better extent in heart failure patients
      that undergo an eight-week high-intensity exercise program (32 exercise sessions) compared to
      the standard of care. The goal of this pilot study is to collect data on safety and efficacy
      of high-intensity interval training in stable heart failure patients to demonstrate better
      physiological and clinical outcomes with fewer long-term health care costs compared to the
      standard of care. Twenty participants with stable heart failure (age range = 40 to 65 years
      of age) will be randomized into two different groups: the standard of care group, in which
      subjects will exercise for 40 minutes at 40 to 60 % of heart rate reserve (HRR) for eight
      weeks (32 sessions); and the high-intensity interval training group, in which subjects will
      perform four sets of 4-minutes at > 85% of HRR, with three minutes of active rest between
      intervals, for six weeks (32 sessions). The functional outcomes measured will be cardiac
      function (i.e. stroke volume, cardiac output, ejection fraction), pulmonary function
      (diffusing capacity, lung volumes, spirometry), exercise capacity (peak oxygen uptake) at
      rest and during exercise before and after eight weeks of exercise training (32 sessions).
      Adverse events related to each exercise training session (i.e. cardiac arrest, myocardial
      infarction during exercise, or within the first hour afterward) as well as arrhythmias will
      be recorded via Holter monitoring 24-hrs post-exercise. Quality of life will also be
      measured. The exercise training will be supervised at Grady Hospital. This novel approach has
      the chance to become impactful to these patients and will challenge the current negative
      perception of high-intensity exercise training in this patient population. The investigators
      anticipate this study will help reform the current exercise guidelines in these participants.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cardiac output
time frame: 8 weeks
description: Measures how much blood is ejected from the left ventricle of the heart per minute (L/min). We will look at this at rest and at peak exercise.
measure: Ejection fraction
time frame: 8 weeks
description: Measures the fraction of blood ejected from the left ventricle at every heart beat (%). We will look at this at rest and at peak exercise.
measure: Pulmonary diffusing capacity
time frame: 8 Weeks
description: Measures gas transfer at the lung in mL/min/mmHg. We will look at this at rest and at peak exercise.
measure: Global longitudinal strain
time frame: 8 Weeks
description: Measures measuring regional or global deformation of the heart measure in (number/s) at rest.
measure: Heart rate variability
time frame: 8 weeks
description: A measurement of either increased sympathetic or reduced vagal activity
measure: Number of arrhythmic events
time frame: over a 24 hr period, before 8 weeks of training and after 8 weeks of training
description: We are examining the number of times there is a recorded irregularity in the force or rhythm of the heartbeat.
measure: Quality of Life
time frame: 8 weeks
description: The MacNew Quality of Life questionnaire will be used to assess the emotional, physical, and social domains
arm group label: High Intensity Group
arm group type: Experimental
description: 3 set of 4 minutes of cycling intense exercise, 4 days per week, for 8 weeks at about 80% to 90% of heart rate reserve
arm group label: Moderate Intensity Group
arm group type: Active Comparator
description: 40 to 47 minutes of continuous cycling exercise at 50% to 60% of heart rate reserve, 4 days per week, for 8 weeks.
intervention type: Other
intervention name: High intensity exercise
description: High intensity exercise, defined as an exercise intensity of > 80% of heart rate reserve. Heart rate reserve is the maximum measured heart rate minus the measured resting heart rate.
arm group label: High Intensity Group
intervention type: Other
intervention name: Moderate intensity exercise
description: Moderate intensity exercise, defined as 50 to 60% of heart rate reserve for 40 to 47 minutes per day, 4 days per week, for 8 weeks. Heart rate reserve is the maximum measured heart rate minus the measured resting heart rate.
arm group label: Moderate Intensity Group
criteria: 
gender: All
minimum age: 40 Years
maximum age: 65 Years
healthy volunteers: No
last name: Gerald S Zavorsky, PhD
role: Principal Investigator
affiliation: Georgia State University
facility: 
country: United States
citation: Wisloff U, Stoylen A, Loennechen JP, Bruvold M, Rognmo O, Haram PM, Tjonna AE, Helgerud J, Slordahl SA, Lee SJ, Videm V, Bye A, Smith GL, Najjar SM, Ellingsen O, Skjaerpe T. Superior cardiovascular effect of aerobic interval training versus moderate continuous training in heart failure patients: a randomized study. Circulation. 2007 Jun 19;115(24):3086-94. doi: 10.1161/CIRCULATIONAHA.106.675041. Epub 2007 Jun 4.
PMID: 17548726
citation: Meyer P, Gayda M, Juneau M, Nigam A. High-intensity aerobic interval exercise in chronic heart failure. Curr Heart Fail Rep. 2013 Jun;10(2):130-8. doi: 10.1007/s11897-013-0130-3.
PMID: 23397179
citation: Flynn KE, Pina IL, Whellan DJ, Lin L, Blumenthal JA, Ellis SJ, Fine LJ, Howlett JG, Keteyian SJ, Kitzman DW, Kraus WE, Miller NH, Schulman KA, Spertus JA, O'Connor CM, Weinfurt KP; HF-ACTION Investigators. Effects of exercise training on health status in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA. 2009 Apr 8;301(14):1451-9. doi: 10.1001/jama.2009.457. Erratum In: JAMA. 2009 Dec 2;302(21):2322.
PMID: 19351942
citation: Guiraud T, Labrunee M, Gaucher-Cazalis K, Despas F, Meyer P, Bosquet L, Gales C, Vaccaro A, Bousquet M, Galinier M, Senard JM, Pathak A. High-intensity interval exercise improves vagal tone and decreases arrhythmias in chronic heart failure. Med Sci Sports Exerc. 2013 Oct;45(10):1861-7. doi: 10.1249/MSS.0b013e3182967559.
PMID: 23591293
citation: Freyssin C, Verkindt C, Prieur F, Benaich P, Maunier S, Blanc P. Cardiac rehabilitation in chronic heart failure: effect of an 8-week, high-intensity interval training versus continuous training. Arch Phys Med Rehabil. 2012 Aug;93(8):1359-64. doi: 10.1016/j.apmr.2012.03.007. Epub 2012 Mar 21.
PMID: 22446291
responsible party type: Sponsor
mesh term: Heart Failure
sharing ipd: Undecided