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/NCT05982769</url>
    </required_header>
    <id_info>
      <org_study_id>21-090</org_study_id>
      <nct_id>NCT05982769</nct_id>
    </id_info>
    <brief_title>Molecular Mechanism of Exercise in Cirrhosis</brief_title>
    <official_title>Molecular Mechanism of Exercise in Cirrhosis</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The Cleveland Clinic</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The Cleveland Clinic</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>
        This study aims to investigate the effects of 12 weeks of resistance or endurance exercise on&#xD;
        patients with cirrhosis. Cirrhotic patients are prone to muscle loss (sarcopenia) and ammonia&#xD;
        build up due to liver dysfunction. The liver which in healthy patients is able to process&#xD;
        ammonia through ureagenesis is unable to do so in cirrhosis and ammonia is taken up either by&#xD;
        the brain causing confusion or the skeletal muscle causing muscle loss or sarcopenia. Primary&#xD;
        sarcopenia occurs in older individuals and can be mitigated by exercise. Secondary sarcopenia&#xD;
        occurs in response to disease such as cancer, chronic kidney disease, multiple sclerosis, and&#xD;
        cirrhosis of all etiologies. Resistance exercise is an excellent stimulator for muscle&#xD;
        protein synthesis and is widely used to build muscle mass and strength but has little benefit&#xD;
        to cardiovascular function. Endurance exercise has shown to be safe in cirrhosis however&#xD;
        there is no set prescription for cirrhosis as there is for other disease. Endurance exercise&#xD;
        is known to promote improved cardiovascular health, improve fatigue, and generates less&#xD;
        ammonia build up than resistance exercise. In patients with low muscle mass it is possible&#xD;
        that endurance exercise alone will be enough to improve muscle mass. There have been few&#xD;
        studies on exercise and cirrhosis, those that exist have shown benefits with endurance&#xD;
        exercise. However there are even more limited studies on resistance exercise and few to no&#xD;
        studies on the molecular mechanisms behind exercise in cirrhosis. Study visits are described&#xD;
        fully in the protocol and consent form. After passing a screening visit patients will undergo&#xD;
        a maximal exercise/fitness test (pre-baseline test) and other body composition measurements.&#xD;
        After the screening and pre-baseline visit randomization will occur (2:2:1 endurance,&#xD;
        resistance, or SOC) arrangements will be made to have the appropriate exercise equipment&#xD;
        given to patients. Once the exercise equipment has arrived a baseline study visit will occur.&#xD;
        After the baseline visit the endurance exercise group will cycle 3 days per week for 60&#xD;
        minutes under the supervision of the study team. The resistance exercise group will perform a&#xD;
        whole body resistance workout 2 days per week for approximately 60 minutes under the&#xD;
        supervision of a study team member.&#xD;
  &#xD;
        Patients in all groups will have the fitness test repeated at weeks 4, 8 and 12. After the 12&#xD;
        weeks of exercise the baseline visits will be repeated and after 2 weeks patients will&#xD;
        complete one final fitness test to examine the effects of de-training.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">April 11, 2022</start_date>
    <completion_date type="Anticipated">August 10, 2027</completion_date>
    <primary_completion_date type="Anticipated">August 10, 2027</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>Other</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change in muscle mass over time</measure>
      <time_frame>day 0 and day 90</time_frame>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Cirrhosis, Liver</condition>
    <arm_group>
      <arm_group_label>Endurance Arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Resistance</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard of Care</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Endurance Training 3 times per week</intervention_name>
      <description>endurance training will be performed from home 3 times per week under the supervision of the research team.</description>
      <arm_group_label>Endurance Arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Resistance Exercise</intervention_name>
      <description>resistance training will be performed from home 2 times per week under the supervision of the research team.</description>
      <arm_group_label>Resistance</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Standard of Care</intervention_name>
      <description>continue usual activity</description>
      <arm_group_label>Standard of Care</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion&#xD;
  &#xD;
            -  Adult patients age 40-65 years of both genders&#xD;
  &#xD;
            -  Diagnosis of cirrhosis by either liver biopsy, clinical, biochemical or imaging&#xD;
               criteria&#xD;
  &#xD;
            -  Child's score 5-10&#xD;
  &#xD;
            -  Model for End Stage Liver Disease (MELD) score less than 21&#xD;
  &#xD;
            -  Abstinence from alcohol and/or other recreational drugs for at least 6 months&#xD;
  &#xD;
            -  Absence of concurrent illnesses (renal, cardiac, pulmonary, cerebrovascular,&#xD;
               malignancy) or medication (anabolic steroids, corticosteroids) intake that affect&#xD;
               skeletal muscle mass, diabetes mellitus (avoid altered muscle protein metabolism), or&#xD;
               use of anticoagulants.&#xD;
  &#xD;
            -  abdominal or liver CT scan within 1 year of enrollment for stratification Exclusion&#xD;
  &#xD;
            -  Active alcohol consumption within 6 weeks of enrollment&#xD;
  &#xD;
            -  Pedal edema (grade 2) above the ankle will be excluded to avoid complications of the&#xD;
               muscle biopsy.&#xD;
  &#xD;
            -  Liver transplant&#xD;
  &#xD;
            -  Active Malignancy&#xD;
  &#xD;
            -  Recent GI bleed (4 weeks)&#xD;
  &#xD;
            -  Hepatic Encephalopathy within previous 6 months&#xD;
  &#xD;
            -  Grade 2 or greater active esophageal varices&#xD;
  &#xD;
            -  Active infection&#xD;
  &#xD;
            -  Large Ascites as defined by clinical imaging&#xD;
  &#xD;
            -  Advanced disease cardiac or pulmonary disease&#xD;
  &#xD;
            -  Use of medications affecting muscle protein turnover including corticosteroids or&#xD;
               medications used to prevent clotting&#xD;
  &#xD;
            -  Clinical lab values that indicate potential poor clotting as determined by the PI&#xD;
  &#xD;
            -  Inability to obtain informed consent; judged likely to be unable to perform exercise&#xD;
               or unlikely to complete the study in the opinion of the investigators&#xD;
  &#xD;
            -  End stage kidney disease as determined by glomerular filtration rate (eGFR) &lt; 15&#xD;
               ml/min/1.73m2 or dialysis&#xD;
  &#xD;
            -  Patients who in the opinion of the PI are unsafe for exercise (failure to pass stress&#xD;
               test)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Srinivasan Dasarathy, MD</last_name>
      <phone>216-318-7010</phone>
      <email>dasaras@ccf.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Annette Bellar</last_name>
      <email>bellara@ccf.org</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Cleveland Clinic</name>
        <address>
          <city>Cleveland</city>
          <state>Ohio</state>
          <zip>44195</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Annette Bellar</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
      <investigator_full_name>Srinivasan Dasarathy</investigator_full_name>
      <investigator_title>Staff Physician</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Liver Cirrhosis</mesh_term>
      <mesh_term>Fibrosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05982769
  org study id: 21-090
  nct id: NCT05982769
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study aims to investigate the effects of 12 weeks of resistance or endurance exercise on
        patients with cirrhosis. Cirrhotic patients are prone to muscle loss (sarcopenia) and ammonia
        build up due to liver dysfunction. The liver which in healthy patients is able to process
        ammonia through ureagenesis is unable to do so in cirrhosis and ammonia is taken up either by
        the brain causing confusion or the skeletal muscle causing muscle loss or sarcopenia. Primary
        sarcopenia occurs in older individuals and can be mitigated by exercise. Secondary sarcopenia
        occurs in response to disease such as cancer, chronic kidney disease, multiple sclerosis, and
        cirrhosis of all etiologies. Resistance exercise is an excellent stimulator for muscle
        protein synthesis and is widely used to build muscle mass and strength but has little benefit
        to cardiovascular function. Endurance exercise has shown to be safe in cirrhosis however
        there is no set prescription for cirrhosis as there is for other disease. Endurance exercise
        is known to promote improved cardiovascular health, improve fatigue, and generates less
        ammonia build up than resistance exercise. In patients with low muscle mass it is possible
        that endurance exercise alone will be enough to improve muscle mass. There have been few
        studies on exercise and cirrhosis, those that exist have shown benefits with endurance
        exercise. However there are even more limited studies on resistance exercise and few to no
        studies on the molecular mechanisms behind exercise in cirrhosis. Study visits are described
        fully in the protocol and consent form. After passing a screening visit patients will undergo
        a maximal exercise/fitness test (pre-baseline test) and other body composition measurements.
        After the screening and pre-baseline visit randomization will occur (2:2:1 endurance,
        resistance, or SOC) arrangements will be made to have the appropriate exercise equipment
        given to patients. Once the exercise equipment has arrived a baseline study visit will occur.
        After the baseline visit the endurance exercise group will cycle 3 days per week for 60
        minutes under the supervision of the study team. The resistance exercise group will perform a
        whole body resistance workout 2 days per week for approximately 60 minutes under the
        supervision of a study team member.
  
        Patients in all groups will have the fitness test repeated at weeks 4, 8 and 12. After the 12
        weeks of exercise the baseline visits will be repeated and after 2 weeks patients will
        complete one final fitness test to examine the effects of de-training.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Other
  masking: None (Open Label)
  measure: Change in muscle mass over time
  time frame: day 0 and day 90
  arm group label: Endurance Arm
  arm group type: Experimental
  arm group label: Resistance
  arm group type: Experimental
  arm group label: Standard of Care
  arm group type: Active Comparator
  intervention type: Behavioral
  intervention name: Endurance Training 3 times per week
  description: endurance training will be performed from home 3 times per week under the supervision of the research team.
  arm group label: Endurance Arm
  intervention type: Behavioral
  intervention name: Resistance Exercise
  description: resistance training will be performed from home 2 times per week under the supervision of the research team.
  arm group label: Resistance
  intervention type: Behavioral
  intervention name: Standard of Care
  description: continue usual activity
  arm group label: Standard of Care
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Srinivasan Dasarathy, MD
  phone: 216-318-7010
  email: dasaras@ccf.org
  last name: Annette Bellar
  email: bellara@ccf.org
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: The Cleveland Clinic
  investigator full name: Srinivasan Dasarathy
  investigator title: Staff Physician
  mesh term: Liver Cirrhosis
  mesh term: Fibrosis
  sharing ipd: No