<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/NCT02223624</url>
  </required_header>
  <id_info>
    <org_study_id>LR49.2013 FHEC13/260 LaTrobeU</org_study_id>
    <secondary_id>LR 49.2013</secondary_id>
    <nct_id>NCT02223624</nct_id>
  </id_info>
  <brief_title>Effect of an Eccentric Exercise Program on Quality of Life and Function in People With Chronic Heart Failure.</brief_title>
  <official_title>Effect of an Eccentrically Biased Aerobic Exercise Program on Quality of Life and Functional Capacity in People With Chronic Heart Failure: A Randomized Controlled Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>La Trobe University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Northern Hospital, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>La Trobe University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many studies have shown that exercise training is beneficial for patients with chronic heart&#xD;
      failure (CHF). Heart Foundation guidelines strongly recommend regular physical activity and&#xD;
      referral to a specifically designed rehabilitation program for all patients with CHF who are&#xD;
      medically stable. Such programs usually comprise aerobic exercises such as walking, and light&#xD;
      weightlifting with care to avoid heavy straining due to stress that this may place on the&#xD;
      heart.&#xD;
&#xD;
      Eccentric contractions are those in which the muscle lengthens as it contracts. Exercise&#xD;
      involving eccentric contractions is known to increase muscle strength and this type of&#xD;
      exercise also requires less oxygen. This is because it requires less power to resist lowering&#xD;
      a weight than it does to lift a weight. Initial evidence suggests that this form of exercise&#xD;
      has favourable outcomes in the frail elderly and those with chronic disease.&#xD;
&#xD;
      This study aims to determine if eccentric exercise can be applied to patients with heart&#xD;
      failure to increase their physical function while using less energy so that exercise is more&#xD;
      tolerable for patients who complain of significant breathlessness and fatigue. This study&#xD;
      also aims to determine if eccentric exercise is a safe alternative exercise option for&#xD;
      patients at risk of negative events.&#xD;
&#xD;
      The investigators propose to run a randomised controlled trial. Eccentric exercise will be&#xD;
      delivered to a group of heart failure patients referred to the existing heart failure&#xD;
      rehabilitation program at the Northern Hospital. The program will consist of eight weeks of&#xD;
      twice weekly exercise of one hour's duration comprising eccentric exercise combined with&#xD;
      walking and light weight training. This will be compared to a group of patients participating&#xD;
      in the current exercise program consisting of light weightlifting and aerobic exercises for&#xD;
      the same length and duration of exercise and also to a third group of patients who will be&#xD;
      wait listed for 8 weeks. Following the completion of the eight week waiting period, these&#xD;
      patients will be offered the option of joining the standard exercise program.&#xD;
&#xD;
      The investigators expect that the eccentric exercise group will have improved walking&#xD;
      capacity and quality of life compared with the traditional program and the wait-list control&#xD;
      group. It is also possible that there is no difference between the eccentric and traditional&#xD;
      program in terms of functional outcomes but that the participants report that eccentric&#xD;
      exercise is easier.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND A systematic literature review we conducted yielded two trials investigating&#xD;
      eccentric exercise in patients with coronary artery disease and two trials in the chronic&#xD;
      heart failure population. Eccentric exercise was reported to be a safe form of exercise for&#xD;
      coronary patients, causing minimal heart and breathing stress and being perceived as &quot;fairly&#xD;
      light&quot; exertion. Eccentric exercise, when compared with concentric exercise (shortening&#xD;
      contractions) resulted in comparable improvements in muscle strength and walking distance,&#xD;
      often with reduced oxygen usage.&#xD;
&#xD;
      With no increase in negative events with coronary patients, recently eccentric exercise has&#xD;
      been trialed in heart failure patients. One trial looked at six-minute walk test differences&#xD;
      in patients with mild heart failure following a program of eccentric or concentric cycling.&#xD;
      They found that although both groups improved their walking distance, the eccentric exercise&#xD;
      was completed at lower levels of work and stable heart rates. A second trial completed&#xD;
      eccentric exercise by descending stairs, compared with participants who climbed stairs and&#xD;
      measured knee muscle strength. They reported that participants found the stair descending&#xD;
      easy with significant improvements in static strength but not eccentric (lengthening) or&#xD;
      concentric (shortening) force. Both of these studies were limited by a population of a small&#xD;
      number (12-15) of participants primarily males, with poorly defined or mild heart failure.&#xD;
&#xD;
      RESEARCH AIMS Given the limited evidence in coronary patients and more specifically heart&#xD;
      failure patients, this current study aims to fill knowledge gaps by looking at the effects of&#xD;
      eccentric exercise on both males and females, with mild to moderate heart failure, of both&#xD;
      heart failure types- systolic (heart contraction problems) and diastolic (heart relaxation&#xD;
      problems). We aim to include measures of both function and quality of life. We will also&#xD;
      monitor compliance and patient satisfaction with the aim of developing a safe and tolerable&#xD;
      exercise program that is feasible for implementation in heart failure rehabilitation&#xD;
      programs.&#xD;
&#xD;
      METHODS Participants will be recruited through The Northern Hospital heart failure outpatient&#xD;
      medical clinics and also through referral to the current rehabilitation program following&#xD;
      inpatient admission or G.P referral. This study will be a prospective, three-armed,&#xD;
      parallel-design, randomised controlled trial with a 1:1:1 ratio. A separate randomisation&#xD;
      procedure will be prepared for each of the three included New York heart association heart&#xD;
      failure classes so that disease severity will not affect the results.&#xD;
&#xD;
      As well as the primary outcomes of walking capacity and quality of life, secondary outcomes&#xD;
      will include lower limb strength and levels of fatigue. We will also monitor adherence,&#xD;
      attendance, pain, and any adverse events occurring in any session.&#xD;
&#xD;
      Demographic and outcome data will be analysed for between group differences at baseline. To&#xD;
      determine whether group 1 improved more than groups 2 and 3 immediately after the 8-week&#xD;
      program, data will be analysed with analysis of covariance using the baseline measures as&#xD;
      covariates. Categorical outcome variables (death or hospital admission) will be analysed with&#xD;
      relative risk ratios. To avoid bias and to maximise the randomisation process, intention to&#xD;
      treat analysis will be utilised. Participants withdrawing from the project will be followed&#xD;
      up where possible. Where data are missing, the carry forward technique will be used, which&#xD;
      assumes that missing data remain constant. Finally, correlations between the secondary&#xD;
      outcome variables and the primary outcome variables will also be examined to detect where&#xD;
      associations exist as well as associations between outcomes and types of heart failure&#xD;
      (systolic or diastolic). Significance level of P&lt;.05 will be used for hypotheses testing.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 2014</start_date>
  <completion_date type="Actual">March 2019</completion_date>
  <primary_completion_date type="Actual">March 2019</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>Factorial Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>functional improvement measured by change in six-minute walk distance</measure>
    <time_frame>post 8-week exercise program and 3-month follow-up</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Quality of life measured by participant questionnaire</measure>
    <time_frame>post 8-week exercise program and 3-month follow-up</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Fatigue as measured by participant questionnaire</measure>
    <time_frame>post 8-week exercise program and 3-month follow-up</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>lower limb strength as measured as a one-repetition maximum leg press</measure>
    <time_frame>post 8-week exercise program and 3-month follow-up</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Chronic Heart Failure</condition>
  <arm_group>
    <arm_group_label>eccentric aerobic exercise group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Eccentric aerobic exercise group: Participants in this group will participate in an eccentric aerobic exercise rehabilitation program for a total of eight weeks, two sessions per week. Outcome measurements will be taken post exercise program and also after a 3 month follow-up period. Each session will be approximately 60 minutes in duration and include approximately 10 minutes of warm up (stretches), eccentric stepper aiming for 20 minutes, walking and light weights, followed by a five minute cool-down period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Concentric aerobic exercise group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Concentric aerobic exercise group (usual care): The length of the concentric aerobic exercise based rehabilitation program will be the same as the study group- twice weekly exercise sessions for 8 weeks. Outcome measurements will also be taken after a 3-month follow-up period.&#xD;
Participants in the concentric aerobic exercise group will participate in the same warm-up and cool down period as the eccentric group. They will also complete walking and light weights. To replace the 20 minutes of eccentric exercise, concentric participants will complete approximately 20 minutes of exercise bike, stair climbing and rowing as able with required rests.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Waiting list control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Waiting list (no exercise): Participants assigned to this group will not receive any intervention during the study period. They will be assessed like other participants at baseline and after eight weeks, but not at three-month follow-up due to ethical concerns around withholding care known to be effective. Given that there is a waiting list for the current exercise program of 4-12 weeks, it is felt that delaying care for a set period of eight weeks is not of ethical concern. Following the completion of assessments, waiting list participants will be able to complete the traditional exercise program as usual but not as participants of the study's experimental groups.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>walking and light weights</intervention_name>
    <arm_group_label>Concentric aerobic exercise group</arm_group_label>
    <arm_group_label>eccentric aerobic exercise group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>eccentric aerobic exercise</intervention_name>
    <arm_group_label>eccentric aerobic exercise group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>concentric aerobic exercise</intervention_name>
    <arm_group_label>Concentric aerobic exercise group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  aged &gt; 18 years&#xD;
&#xD;
          -  a clinical diagnosis of heart failure either systolic or diastolic on transthoracic&#xD;
             echocardiogram&#xD;
&#xD;
          -  mild to moderate heart failure&#xD;
&#xD;
          -  medically stable heart failure&#xD;
&#xD;
          -  have received approval when assessed by the group physiotherapist to participate in&#xD;
             the exercise program as is usual practice. Where concerns arise during assessment,&#xD;
             clearance will be sought from the treating cardiologist.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  hospitalisation for a CHF exacerbation within the previous month&#xD;
&#xD;
          -  severe heart failure classified as level four on the New York heart association&#xD;
             classification (short of breath at rest)&#xD;
&#xD;
          -  unstable medical condition such as uncontrolled angina, diabetes or hypertension&#xD;
&#xD;
          -  dementia or a psychological disorder that would interfere with participation in group&#xD;
             exercise&#xD;
&#xD;
          -  participation in a cardiac or heart failure rehabilitation program in the prior six&#xD;
             months&#xD;
&#xD;
          -  contraindications to exercise (ie aneurysm, valvular disease)&#xD;
&#xD;
          -  the presence of any pre-existing neurological or musculoskeletal condition, for&#xD;
             example stroke, that on assessment is deemed to interfere with exercise participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Rachel E Ellis</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northern Hospital, Australia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Kwang Lim</last_name>
    <role>Principal Investigator</role>
    <affiliation>Melbourne Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Karen J Dodd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Victoria University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anne E Holland</last_name>
    <role>Principal Investigator</role>
    <affiliation>La Trobe University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Nora Shields</last_name>
    <role>Principal Investigator</role>
    <affiliation>La Trobe University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Northern Hospital</name>
      <address>
        <city>Epping</city>
        <state>Victoria</state>
        <zip>3076</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>February 19, 2020</last_update_submitted>
  <last_update_submitted_qc>February 19, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>La Trobe University</investigator_affiliation>
    <investigator_full_name>Rachel Ellis</investigator_full_name>
    <investigator_title>Clinical Leader Physiotherapist</investigator_title>
  </responsible_party>
  <keyword>eccentric</keyword>
  <keyword>exercise</keyword>
  <keyword>heart disease</keyword>
  <keyword>chronic heart failure</keyword>
  <keyword>rehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <!-- 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/NCT02223624
org study id: LR49.2013 FHEC13/260 LaTrobeU
secondary id: LR 49.2013
nct id: NCT02223624
lead sponsor: 
collaborator: 
has dmc: No
Many studies have shown that exercise training is beneficial for patients with chronic heart
      failure (CHF). Heart Foundation guidelines strongly recommend regular physical activity and
      referral to a specifically designed rehabilitation program for all patients with CHF who are
      medically stable. Such programs usually comprise aerobic exercises such as walking, and light
      weightlifting with care to avoid heavy straining due to stress that this may place on the
      heart.

      Eccentric contractions are those in which the muscle lengthens as it contracts. Exercise
      involving eccentric contractions is known to increase muscle strength and this type of
      exercise also requires less oxygen. This is because it requires less power to resist lowering
      a weight than it does to lift a weight. Initial evidence suggests that this form of exercise
      has favourable outcomes in the frail elderly and those with chronic disease.

      This study aims to determine if eccentric exercise can be applied to patients with heart
      failure to increase their physical function while using less energy so that exercise is more
      tolerable for patients who complain of significant breathlessness and fatigue. This study
      also aims to determine if eccentric exercise is a safe alternative exercise option for
      patients at risk of negative events.

      The investigators propose to run a randomised controlled trial. Eccentric exercise will be
      delivered to a group of heart failure patients referred to the existing heart failure
      rehabilitation program at the Northern Hospital. The program will consist of eight weeks of
      twice weekly exercise of one hour's duration comprising eccentric exercise combined with
      walking and light weight training. This will be compared to a group of patients participating
      in the current exercise program consisting of light weightlifting and aerobic exercises for
      the same length and duration of exercise and also to a third group of patients who will be
      wait listed for 8 weeks. Following the completion of the eight week waiting period, these
      patients will be offered the option of joining the standard exercise program.

      The investigators expect that the eccentric exercise group will have improved walking
      capacity and quality of life compared with the traditional program and the wait-list control
      group. It is also possible that there is no difference between the eccentric and traditional
      program in terms of functional outcomes but that the participants report that eccentric
      exercise is easier.
BACKGROUND A systematic literature review we conducted yielded two trials investigating
      eccentric exercise in patients with coronary artery disease and two trials in the chronic
      heart failure population. Eccentric exercise was reported to be a safe form of exercise for
      coronary patients, causing minimal heart and breathing stress and being perceived as "fairly
      light" exertion. Eccentric exercise, when compared with concentric exercise (shortening
      contractions) resulted in comparable improvements in muscle strength and walking distance,
      often with reduced oxygen usage.

      With no increase in negative events with coronary patients, recently eccentric exercise has
      been trialed in heart failure patients. One trial looked at six-minute walk test differences
      in patients with mild heart failure following a program of eccentric or concentric cycling.
      They found that although both groups improved their walking distance, the eccentric exercise
      was completed at lower levels of work and stable heart rates. A second trial completed
      eccentric exercise by descending stairs, compared with participants who climbed stairs and
      measured knee muscle strength. They reported that participants found the stair descending
      easy with significant improvements in static strength but not eccentric (lengthening) or
      concentric (shortening) force. Both of these studies were limited by a population of a small
      number (12-15) of participants primarily males, with poorly defined or mild heart failure.

      RESEARCH AIMS Given the limited evidence in coronary patients and more specifically heart
      failure patients, this current study aims to fill knowledge gaps by looking at the effects of
      eccentric exercise on both males and females, with mild to moderate heart failure, of both
      heart failure types- systolic (heart contraction problems) and diastolic (heart relaxation
      problems). We aim to include measures of both function and quality of life. We will also
      monitor compliance and patient satisfaction with the aim of developing a safe and tolerable
      exercise program that is feasible for implementation in heart failure rehabilitation
      programs.

      METHODS Participants will be recruited through The Northern Hospital heart failure outpatient
      medical clinics and also through referral to the current rehabilitation program following
      inpatient admission or G.P referral. This study will be a prospective, three-armed,
      parallel-design, randomised controlled trial with a 1:1:1 ratio. A separate randomisation
      procedure will be prepared for each of the three included New York heart association heart
      failure classes so that disease severity will not affect the results.

      As well as the primary outcomes of walking capacity and quality of life, secondary outcomes
      will include lower limb strength and levels of fatigue. We will also monitor adherence,
      attendance, pain, and any adverse events occurring in any session.

      Demographic and outcome data will be analysed for between group differences at baseline. To
      determine whether group 1 improved more than groups 2 and 3 immediately after the 8-week
      program, data will be analysed with analysis of covariance using the baseline measures as
      covariates. Categorical outcome variables (death or hospital admission) will be analysed with
      relative risk ratios. To avoid bias and to maximise the randomisation process, intention to
      treat analysis will be utilised. Participants withdrawing from the project will be followed
      up where possible. Where data are missing, the carry forward technique will be used, which
      assumes that missing data remain constant. Finally, correlations between the secondary
      outcome variables and the primary outcome variables will also be examined to detect where
      associations exist as well as associations between outcomes and types of heart failure
      (systolic or diastolic). Significance level of P<.05 will be used for hypotheses testing.
allocation: Randomized
intervention model: Factorial Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: functional improvement measured by change in six-minute walk distance
time frame: post 8-week exercise program and 3-month follow-up
measure: Quality of life measured by participant questionnaire
time frame: post 8-week exercise program and 3-month follow-up
measure: Fatigue as measured by participant questionnaire
time frame: post 8-week exercise program and 3-month follow-up
measure: lower limb strength as measured as a one-repetition maximum leg press
time frame: post 8-week exercise program and 3-month follow-up
arm group label: eccentric aerobic exercise group
arm group type: Experimental
description: Eccentric aerobic exercise group: Participants in this group will participate in an eccentric aerobic exercise rehabilitation program for a total of eight weeks, two sessions per week. Outcome measurements will be taken post exercise program and also after a 3 month follow-up period. Each session will be approximately 60 minutes in duration and include approximately 10 minutes of warm up (stretches), eccentric stepper aiming for 20 minutes, walking and light weights, followed by a five minute cool-down period.
arm group label: Concentric aerobic exercise group
arm group type: Active Comparator
description: Concentric aerobic exercise group (usual care): The length of the concentric aerobic exercise based rehabilitation program will be the same as the study group- twice weekly exercise sessions for 8 weeks. Outcome measurements will also be taken after a 3-month follow-up period.
Participants in the concentric aerobic exercise group will participate in the same warm-up and cool down period as the eccentric group. They will also complete walking and light weights. To replace the 20 minutes of eccentric exercise, concentric participants will complete approximately 20 minutes of exercise bike, stair climbing and rowing as able with required rests.
arm group label: Waiting list control
arm group type: No Intervention
description: Waiting list (no exercise): Participants assigned to this group will not receive any intervention during the study period. They will be assessed like other participants at baseline and after eight weeks, but not at three-month follow-up due to ethical concerns around withholding care known to be effective. Given that there is a waiting list for the current exercise program of 4-12 weeks, it is felt that delaying care for a set period of eight weeks is not of ethical concern. Following the completion of assessments, waiting list participants will be able to complete the traditional exercise program as usual but not as participants of the study's experimental groups.
intervention type: Other
intervention name: walking and light weights
arm group label: Concentric aerobic exercise group
arm group label: eccentric aerobic exercise group
intervention type: Other
intervention name: eccentric aerobic exercise
arm group label: eccentric aerobic exercise group
intervention type: Other
intervention name: concentric aerobic exercise
arm group label: Concentric aerobic exercise group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rachel E Ellis
role: Principal Investigator
affiliation: Northern Hospital, Australia
last name: Kwang Lim
role: Principal Investigator
affiliation: Melbourne Health
last name: Karen J Dodd
role: Principal Investigator
affiliation: Victoria University
last name: Anne E Holland
role: Principal Investigator
affiliation: La Trobe University
last name: Nora Shields
role: Principal Investigator
affiliation: La Trobe University
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: La Trobe University
investigator full name: Rachel Ellis
investigator title: Clinical Leader Physiotherapist
mesh term: Heart Failure