xml: <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/NCT06016192</url>
    </required_header>
    <id_info>
      <org_study_id>PCS_Training_01</org_study_id>
      <nct_id>NCT06016192</nct_id>
    </id_info>
    <brief_title>Aerobic Training for Rehabilitation of Patients With Post Covid-19 Syndrome</brief_title>
    <official_title>Medical Rehabilitation of Patients With Long-term Post-Covid-19 Syndrome - a Comparison of Aerobic Interval and Continuous Training</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Witten/Herdecke</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Institut für Rehabilitationsforschung Norderney</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Witten/Herdecke</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>
        Post-COVID-19 syndrome (PCS) occurs as a sequelae after acute infection with the SARS-CoV-2&#xD;
        virus (COVID-19 infection). PCS is defined as symptom persistence over a period of 12 weeks&#xD;
        from infection and/or the appearance of new symptoms in this period. While the majority of&#xD;
        affected patients experience a gradual healing process without targeted treatment, the need&#xD;
        for effective medical rehabilitation is high at least for patients with persistent PCS.&#xD;
  &#xD;
        Given that physical exercise has been shown to be beneficial in multiple pathologies such as&#xD;
        cardiovascular diseases, neuropathic disorders, and pulmonary diseases it has been suggested&#xD;
        that physical exercise including aerobic training could exert beneficial effects also in PCS.&#xD;
        This study aims to analyse the use of moderate-intensity aerobic exercise training for&#xD;
        medical rehabilitation of PCS patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Post-COVID-19 syndrome (PCS) is a condition that occurs following an acute infection with the&#xD;
        SARS-CoV-2 virus (COVID-19). PCS is characterized by symptom persistence for at least 12&#xD;
        weeks after the infection or the emergence of new symptoms during this period. Current&#xD;
        guidelines propose several criteria for diagnosing PCS, including persistent symptoms from&#xD;
        the acute COVID-19 phase, new symptoms leading to health limitations, symptoms assumed to be&#xD;
        related to COVID-19 after the acute phase, and worsening of pre-existing underlying&#xD;
        conditions. PCS is a complex and multisystemic disorder, with symptoms ranging from chronic&#xD;
        fatigue, decreased physical performance, muscular weakness, and pain to cognitive impairment&#xD;
        (often referred to as brain fog) and mental and psychological distress resembling a&#xD;
        post-traumatic stress reaction. The exact causes of PCS are not fully understood but may&#xD;
        involve processes such as endothelial dysfunction, cytokine storm, and increased oxidative&#xD;
        stress affecting various organs and structures in the body. The incidence of PCS varies&#xD;
        depending on the population studied and the severity of symptoms considered, with estimates&#xD;
        ranging from 7.5% to 41% among non-hospitalized patients with acute infection.&#xD;
  &#xD;
        Medical rehabilitation is essential for patients with persistent PCS, but there are limited&#xD;
        studies on its efficacy, especially in the context of aerobic endurance training. Physical&#xD;
        exercise, including aerobic training, has shown positive effects in various diseases, and it&#xD;
        is suggested that it may be beneficial for PCS as well. However, there is limited evidence&#xD;
        regarding the effectiveness of aerobic endurance training in reducing the burden of decreased&#xD;
        physical performance in PCS. Moreover, there is a lack of guidelines for PCS patients related&#xD;
        to exercise-based rehabilitation. Aerobic endurance training has been proven to have positive&#xD;
        effects on multiple physiological functions and is recommended for chronic heart and&#xD;
        pulmonary diseases. Studies have also suggested that aerobic interval training may be&#xD;
        advantageous for PCS patients, as it reduces ventilatory demand and may alleviate dyspnea and&#xD;
        breathing effort. This study aims to investigate the efficacy of moderate-intensity aerobic&#xD;
        endurance training performed as either continuous training and interval training for the&#xD;
        medical rehabilitation of PCS patients.&#xD;
  &#xD;
        The study will include PCS patients referred for inpatient medical rehabilitation in Germany&#xD;
        with a history of (at least one) Covid-19 infection and ongoing or newly expressed&#xD;
        performance deficits lasting for at least 3 months prior to recruitment. Performance deficits&#xD;
        will be documented according to the recent consensus statement, with the cluster of lead&#xD;
        symptoms including fatigue/exercise intolerance, shortness of breath, and cognitive&#xD;
        dysfunction impairing activity of daily living and everyday functioning. A detailed clinical&#xD;
        workup will be performed, and the history of comorbidities and current medication will be&#xD;
        documented. After admission, patients will be randomized to a continuous training (CT) or&#xD;
        interval training (IT) group. Patients will receive individual medical rehabilitation&#xD;
        including a combination of strength, respiratory and cognitive training, as well as physio-,&#xD;
        psycho- and nutrition therapy, unaltered for both groups. Data on medical rehabilitation&#xD;
        including prescriptions of therapeutic actions and participation will be recorded for all&#xD;
        patients. Symptom-limited spiroergometry at admission and after 4-6 weeks of inpatient&#xD;
        rehabilitation (before discharge) will be performed to analyze improvements in exercise&#xD;
        capacity. Validated questionnaires will be used to document patients' disease perception.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">August 1, 2021</start_date>
    <completion_date type="Actual">May 31, 2023</completion_date>
    <primary_completion_date type="Actual">November 30, 2022</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>
      <intervention_model_description>Two-arm randomized</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in Cardiorespiratory Fitness (CRF)</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>CRF will be measured as peak oxygen uptake (VO2peak) determined by spiroergometry</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Change in Submaximal Cardiorespiratory Fitness (CRF)</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Submaximal CRF will be measured as submaximal oxygen uptake (VO2 at ventilatory threshold 1 [VT1]) determined by spiroergometry</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Fatigue</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Fatigue will be assessed using the &quot;The Multidimensional Fatigue Inventory (MFI20)&quot;.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Work requirements and workload</measure>
      <time_frame>Baseline</time_frame>
      <description>Work requirements and workload will be assessed using the &quot;Workability Index (WAI)&quot;.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change Health-related quality of life</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Health-related quality of life will be assessed using the &quot;RAND 36-Item Health Survey (SF-36)&quot;.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Wellbeing</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Wellbeing will be assessed using the &quot;WHO-5 Well-Being Index&quot;.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in Depression and Anxiety</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Depression and Anxiety will be assessed using the Hospital Anxiety and Depression Scale (HADS)</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Change in training load</measure>
      <time_frame>Daily, from baseline to week 4 (i. e. before discharge)</time_frame>
      <description>Training load will be assessed by analysis of documented ergometer settings (mean Watts)</description>
    </other_outcome>
    <other_outcome>
      <measure>Training participation</measure>
      <time_frame>Daily, from baseline to week 4 (i. e. before discharge)</time_frame>
      <description>Training participation will be assessed by number of performed ergometer training sessions</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in minute ventilation (VE)</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Minute ventilation will be determined by spiroergometry measuring breath-by-breath volumes (ml)</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in carbon dioxide production (VCO2)</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Carbon dioxide production (VCO2) will be determined by spiroergometry measuring breath-by-breath volumes of exhaled carbon dioxide (ml)</description>
    </other_outcome>
    <other_outcome>
      <measure>Change in submaximal and maximal workload (Watt)</measure>
      <time_frame>Baseline and week 4 (i. e. before discharge)</time_frame>
      <description>Submaxmal and maximal workload (Watt) will be determined by spiroergometry</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Actual">139</enrollment>
    <condition>Post-COVID-19 Syndrome</condition>
    <condition>Long-COVID-19 Syndrome</condition>
    <arm_group>
      <arm_group_label>Continuous aerobic training</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Moderate continous endurance training, ergometer</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Interval aerobic training</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Moderate intensity interval training, ergometer</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Aerobic Exercise Training</intervention_name>
      <description>Physical activity performed as controlled aerobic exercise training on ergometer</description>
      <arm_group_label>Continuous aerobic training</arm_group_label>
      <arm_group_label>Interval aerobic training</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  a history of (at least one) Covid-19 infection&#xD;
  &#xD;
            -  ongoing or newly expressed performance deficits lasting for at least 3 months prior to&#xD;
               recruitment&#xD;
  &#xD;
            -  referral to inpatient rehabilitation&#xD;
  &#xD;
            -  signed informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  unstable condition&#xD;
  &#xD;
            -  incapable of understanding study information&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Clinic Königsfeld</name>
        <address>
          <city>Ennepetal</city>
          <state>NRW</state>
          <zip>58256</zip>
          <country>Germany</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Germany</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 29, 2023</study_first_posted>
    <last_update_submitted>August 29, 2023</last_update_submitted>
    <last_update_submitted_qc>August 29, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>COVID-19</keyword>
    <keyword>Fatigue</keyword>
    <keyword>Rehabilitation</keyword>
    <keyword>Exercise Training</keyword>
    <keyword>Infectious Disease</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>COVID-19</mesh_term>
      <mesh_term>Post-Acute COVID-19 Syndrome</mesh_term>
      <mesh_term>Syndrome</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06016192
  org study id: PCS_Training_01
  nct id: NCT06016192
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Post-COVID-19 syndrome (PCS) occurs as a sequelae after acute infection with the SARS-CoV-2
        virus (COVID-19 infection). PCS is defined as symptom persistence over a period of 12 weeks
        from infection and/or the appearance of new symptoms in this period. While the majority of
        affected patients experience a gradual healing process without targeted treatment, the need
        for effective medical rehabilitation is high at least for patients with persistent PCS.
  
        Given that physical exercise has been shown to be beneficial in multiple pathologies such as
        cardiovascular diseases, neuropathic disorders, and pulmonary diseases it has been suggested
        that physical exercise including aerobic training could exert beneficial effects also in PCS.
        This study aims to analyse the use of moderate-intensity aerobic exercise training for
        medical rehabilitation of PCS patients.
  Post-COVID-19 syndrome (PCS) is a condition that occurs following an acute infection with the
        SARS-CoV-2 virus (COVID-19). PCS is characterized by symptom persistence for at least 12
        weeks after the infection or the emergence of new symptoms during this period. Current
        guidelines propose several criteria for diagnosing PCS, including persistent symptoms from
        the acute COVID-19 phase, new symptoms leading to health limitations, symptoms assumed to be
        related to COVID-19 after the acute phase, and worsening of pre-existing underlying
        conditions. PCS is a complex and multisystemic disorder, with symptoms ranging from chronic
        fatigue, decreased physical performance, muscular weakness, and pain to cognitive impairment
        (often referred to as brain fog) and mental and psychological distress resembling a
        post-traumatic stress reaction. The exact causes of PCS are not fully understood but may
        involve processes such as endothelial dysfunction, cytokine storm, and increased oxidative
        stress affecting various organs and structures in the body. The incidence of PCS varies
        depending on the population studied and the severity of symptoms considered, with estimates
        ranging from 7.5% to 41% among non-hospitalized patients with acute infection.
  
        Medical rehabilitation is essential for patients with persistent PCS, but there are limited
        studies on its efficacy, especially in the context of aerobic endurance training. Physical
        exercise, including aerobic training, has shown positive effects in various diseases, and it
        is suggested that it may be beneficial for PCS as well. However, there is limited evidence
        regarding the effectiveness of aerobic endurance training in reducing the burden of decreased
        physical performance in PCS. Moreover, there is a lack of guidelines for PCS patients related
        to exercise-based rehabilitation. Aerobic endurance training has been proven to have positive
        effects on multiple physiological functions and is recommended for chronic heart and
        pulmonary diseases. Studies have also suggested that aerobic interval training may be
        advantageous for PCS patients, as it reduces ventilatory demand and may alleviate dyspnea and
        breathing effort. This study aims to investigate the efficacy of moderate-intensity aerobic
        endurance training performed as either continuous training and interval training for the
        medical rehabilitation of PCS patients.
  
        The study will include PCS patients referred for inpatient medical rehabilitation in Germany
        with a history of (at least one) Covid-19 infection and ongoing or newly expressed
        performance deficits lasting for at least 3 months prior to recruitment. Performance deficits
        will be documented according to the recent consensus statement, with the cluster of lead
        symptoms including fatigue/exercise intolerance, shortness of breath, and cognitive
        dysfunction impairing activity of daily living and everyday functioning. A detailed clinical
        workup will be performed, and the history of comorbidities and current medication will be
        documented. After admission, patients will be randomized to a continuous training (CT) or
        interval training (IT) group. Patients will receive individual medical rehabilitation
        including a combination of strength, respiratory and cognitive training, as well as physio-,
        psycho- and nutrition therapy, unaltered for both groups. Data on medical rehabilitation
        including prescriptions of therapeutic actions and participation will be recorded for all
        patients. Symptom-limited spiroergometry at admission and after 4-6 weeks of inpatient
        rehabilitation (before discharge) will be performed to analyze improvements in exercise
        capacity. Validated questionnaires will be used to document patients' disease perception.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Two-arm randomized
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Change in Cardiorespiratory Fitness (CRF)
  time frame: Baseline and week 4 (i. e. before discharge)
  description: CRF will be measured as peak oxygen uptake (VO2peak) determined by spiroergometry
  measure: Change in Submaximal Cardiorespiratory Fitness (CRF)
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Submaximal CRF will be measured as submaximal oxygen uptake (VO2 at ventilatory threshold 1 [VT1]) determined by spiroergometry
  measure: Change in Fatigue
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Fatigue will be assessed using the "The Multidimensional Fatigue Inventory (MFI20)".
  measure: Work requirements and workload
  time frame: Baseline
  description: Work requirements and workload will be assessed using the "Workability Index (WAI)".
  measure: Change Health-related quality of life
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Health-related quality of life will be assessed using the "RAND 36-Item Health Survey (SF-36)".
  measure: Wellbeing
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Wellbeing will be assessed using the "WHO-5 Well-Being Index".
  measure: Change in Depression and Anxiety
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Depression and Anxiety will be assessed using the Hospital Anxiety and Depression Scale (HADS)
  measure: Change in training load
  time frame: Daily, from baseline to week 4 (i. e. before discharge)
  description: Training load will be assessed by analysis of documented ergometer settings (mean Watts)
  measure: Training participation
  time frame: Daily, from baseline to week 4 (i. e. before discharge)
  description: Training participation will be assessed by number of performed ergometer training sessions
  measure: Change in minute ventilation (VE)
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Minute ventilation will be determined by spiroergometry measuring breath-by-breath volumes (ml)
  measure: Change in carbon dioxide production (VCO2)
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Carbon dioxide production (VCO2) will be determined by spiroergometry measuring breath-by-breath volumes of exhaled carbon dioxide (ml)
  measure: Change in submaximal and maximal workload (Watt)
  time frame: Baseline and week 4 (i. e. before discharge)
  description: Submaxmal and maximal workload (Watt) will be determined by spiroergometry
  arm group label: Continuous aerobic training
  arm group type: Active Comparator
  description: Moderate continous endurance training, ergometer
  arm group label: Interval aerobic training
  arm group type: Experimental
  description: Moderate intensity interval training, ergometer
  intervention type: Behavioral
  intervention name: Aerobic Exercise Training
  description: Physical activity performed as controlled aerobic exercise training on ergometer
  arm group label: Continuous aerobic training
  arm group label: Interval aerobic training
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: Germany
  responsible party type: Sponsor
  mesh term: COVID-19
  mesh term: Post-Acute COVID-19 Syndrome
  mesh term: Syndrome