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/NCT06040814</url>
    </required_header>
    <id_info>
      <org_study_id>202201561B0</org_study_id>
      <nct_id>NCT06040814</nct_id>
    </id_info>
    <brief_title>Microbiota, Sarcopenia, and Hepatic Encephalopathy Change in Cirrhotic Patients Before and After Rehabilitation</brief_title>
    <official_title>To Explore the Changes of Fecal Microbiota Before and After Treatment in Patients With Liver Cirrhosis Complicated With Hepatic Encephalopathy or Sarcopenia as a Reference for Future Fecal Microbiota Transplantation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chang Gung Memorial Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Chang Gung Memorial Hospital</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>
        Through this plan, it will provide many benefits to patients with liver cirrhosis complicated&#xD;
        with sarcopenia and/or hepatic encephalopathy, their family members, and the government in&#xD;
        Taiwan:&#xD;
  &#xD;
          1. To explore the changes of fecal microbiota before and after treatment such as resistance&#xD;
             training rehabilitation in patients with liver cirrhosis complicated with sarcopenia&#xD;
             and/or hepatic encephalopathy as a reference for future fecal microbiota&#xD;
             transplantation;&#xD;
  &#xD;
          2. To measure the changes of sarcopenia level before and after rehabilitation;&#xD;
  &#xD;
          3. To measure the changes of hepatic encephalopathy level before and after rehabilitation.&#xD;
  &#xD;
        These study results will certainly bring updated diagnostic tool, latest treatment options,&#xD;
        avoid serious sequelae and reduce medical expenditure.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Chronic liver disease is notorious as Taiwan's national disease and more than 4,000 patients&#xD;
        died of liver cirrhosis each year in Taiwan. Hepatic encephalopathy (HE) manifests from&#xD;
        minimal HE (MHE) to overt HE (OHE). The diagnosis of covert HE (CHE) requires psychometric&#xD;
        tests or neurophysiological tools. However, psychometric testing for patients with CHE is&#xD;
        often neglected in Taiwan. On the basis of the capability to detect all forms of HE, further&#xD;
        investigation on the association of HE with fecal microbiota alterations is urgently needed.&#xD;
        It is because HE is associated with dysregulation in the gut-liver-brain axis, which includes&#xD;
        intestinal barrier dysfunction and gut microbial dysbiosis. However, despite current standard&#xD;
        of care (SOC) therapy i.e., lactulose and rifaximin, there remains a subset of patients who&#xD;
        continue to suffer recurrence, which leads to further cognitive impairment, sarcopenia and&#xD;
        readmissions. There remain several factors that can influence the microbiota, such as&#xD;
        demographics (geographic area, sex and diet), etiology, drugs, interventions, and ﬁnally the&#xD;
        sampling compartment. These factors need to be controlled for and considered in the&#xD;
        interpretation of future studies. The microbiome dynamic change during rehabilitation in&#xD;
        cirrhotic patients with sarcopenia has never been studied and is worth exploring.&#xD;
  &#xD;
        Furthermore, from our previous study, the investigators have shown that one-year efficacy of&#xD;
        rifaximin add-on to lactulose is superior to lactulose alone in patients with cirrhosis&#xD;
        complicated with recurrent HE in Taiwan. The investigators also have preliminary data showing&#xD;
        that rehabilitation could improve patient's sarcopenia. Further cohort validation is urgently&#xD;
        required.&#xD;
  &#xD;
        Our innovative research purposes:&#xD;
  &#xD;
          1. To explore the changes of fecal microbiota before and after treatment such as resistance&#xD;
             training rehabilitation as a reference for future fecal microbiota transplantation;&#xD;
  &#xD;
          2. To measure the changes of sarcopenia levels before and after rehabilitation&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">December 1, 2022</start_date>
    <completion_date type="Anticipated">November 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">November 30, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Handgrip Strength</measure>
      <time_frame>6 months</time_frame>
      <description>Handgrip strength is an assessment of muscle strength. The cutoff value of the handgrip is &lt; 30 kg in men and &lt; 20 kg in women.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Short Physical Performance Battery (SPPB)</measure>
      <time_frame>6 months</time_frame>
      <description>Short Physical Performance Battery (SPPB) is an assessment of physical performance. The cut-off value of the Short Physical Performance Battery (SPPB) score for determining sarcopenia is ≤ 9.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dual-energy X-ray absorptiometry (DEXA)</measure>
      <time_frame>6 months</time_frame>
      <description>Dual-energy X-ray absorptiometry (DXA) is the gold-standard technique in the analysis of body composition. The cut-off value of appendicular skeletal muscle mass (ASMI) score for determining sarcopenia is &lt; 7.0 kg/m^2 in men and &lt; 5.4 kg/m^2 in women.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Mini-Mental Status Examination (MMSE)</measure>
      <time_frame>6 months</time_frame>
      <description>Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. The cut-off value of Mini-Mental State Examination (MMSE) score is &lt; 28.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Psychometric Hepatic Encephalopathy Score (PHES)</measure>
      <time_frame>6 months</time_frame>
      <description>The psychometric hepatic encephalopathy score (PHES) is the gold standard for diagnosing minimal hepatic encephalopathy (MHE). The cut-off value of the Psychometric Hepatic Encephalopathy Score (PHES) for determining minimal hepatic encephalopathy (MHE) is ≤ -4.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Animal Naming Test (ANT)</measure>
      <time_frame>6 months</time_frame>
      <description>The animal naming test (ANT) is an easy tool for the assessment of hepatic encephalopathy (HE). The cut-off value of the Animal Naming Test (ANT) score for determining hepatic encephalopathy (HE) is ≤ 19.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Blood cytokine levels [IL-6]</measure>
      <time_frame>6 months</time_frame>
      <description>Serum IL-6 level (pg/ mL)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Blood ammonia levels [NH3]</measure>
      <time_frame>6 months</time_frame>
      <description>Serum ammonia level (μg/dL)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Electroencephalogram (EEG)</measure>
      <time_frame>6 months</time_frame>
      <description>Quantified EEG spectral analysis:&#xD;
  Grade 0: Mean dominant frequency (MDF)&gt; 6.8 Hz and no theta nor delta wave Grade 1: MDF &gt; 6.8Hz and theta wave relative power ≧35% Grade 2: MDF≤ 6.8 Hz and delta wave relative power&lt;49% Grade 3: MDF≤ 6.8 Hz and delta wave relative power≧49%</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Fecal Microbiota</measure>
      <time_frame>6 months</time_frame>
      <description>Check fecal microbiota taxonomy profile and relative abundance changes.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Hepatic Encephalopathy</condition>
    <arm_group>
      <arm_group_label>Rehabilitation Training</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Rehabilitation Training is provided to patients with Liver Cirrhosis combined with sarcopenia.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>No-Rehabilitation Training</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>No extra training is provided to patients with Liver Cirrhosis combined with sarcopenia.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Rehabilitation Training</intervention_name>
      <description>12 week Rehabilitation Training course</description>
      <arm_group_label>Rehabilitation Training</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with liver cirrhosis&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  unstable vital sign such as shock, coma or intubation status&#xD;
  &#xD;
            -  Non-curative hepatocellular carcinoma (cannot receive operation, radiofrequency&#xD;
               ablation, liver transplantation,etc&#xD;
  &#xD;
            -  Un-curative malignancies&#xD;
  &#xD;
            -  Poor-controlled diabetes mellitus (HbA1C≧8)&#xD;
  &#xD;
            -  Active alcoholism (male alcohol ≧40g/day, or ≧140g/week; female ≧ 30g/day, or&#xD;
               ≧70g/week&#xD;
  &#xD;
            -  Psychiatric comorbidities&#xD;
  &#xD;
            -  Neurologic comorbidities like Alzheimer's, Parkinson's, stroke with neurological&#xD;
               deficit&#xD;
  &#xD;
            -  Unable to speak&#xD;
  &#xD;
            -  Bed-ridden status&#xD;
  &#xD;
            -  Post- Liver transplantation.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>CHIEN-HAO HUANG</last_name>
      <role>Principal Investigator</role>
      <affiliation>Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>CHIEN-HAO HUANG, MD</last_name>
      <phone>+886 9753 66128</phone>
      <email>q12248@cgmh.org.tw</email>
    </overall_contact>
    <location>
      <facility>
        <name>Chang Gung Memorial Hospital</name>
        <address>
          <city>Taoyuan</city>
          <zip>333</zip>
          <country>Taiwan</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>CHIEN-HUNG CHEN, MD</last_name>
        <phone>+886 9753 66128</phone>
        <email>q12248@cgmh.org.tw</email>
      </contact>
    </location>
    <location_countries>
      <country>Taiwan</country>
    </location_countries>
    <verification_date>December 2022</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>September 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Liver cirrhosis</keyword>
    <keyword>Hepatic encephalopathy</keyword>
    <keyword>Psychometric test</keyword>
    <keyword>Sarcopenia</keyword>
    <keyword>Fecal microbiota</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hepatic Encephalopathy</mesh_term>
      <mesh_term>Sarcopenia</mesh_term>
      <mesh_term>Brain Diseases</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/NCT06040814
  org study id: 202201561B0
  nct id: NCT06040814
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Through this plan, it will provide many benefits to patients with liver cirrhosis complicated
        with sarcopenia and/or hepatic encephalopathy, their family members, and the government in
        Taiwan:
  
          1. To explore the changes of fecal microbiota before and after treatment such as resistance
             training rehabilitation in patients with liver cirrhosis complicated with sarcopenia
             and/or hepatic encephalopathy as a reference for future fecal microbiota
             transplantation;
  
          2. To measure the changes of sarcopenia level before and after rehabilitation;
  
          3. To measure the changes of hepatic encephalopathy level before and after rehabilitation.
  
        These study results will certainly bring updated diagnostic tool, latest treatment options,
        avoid serious sequelae and reduce medical expenditure.
  Chronic liver disease is notorious as Taiwan's national disease and more than 4,000 patients
        died of liver cirrhosis each year in Taiwan. Hepatic encephalopathy (HE) manifests from
        minimal HE (MHE) to overt HE (OHE). The diagnosis of covert HE (CHE) requires psychometric
        tests or neurophysiological tools. However, psychometric testing for patients with CHE is
        often neglected in Taiwan. On the basis of the capability to detect all forms of HE, further
        investigation on the association of HE with fecal microbiota alterations is urgently needed.
        It is because HE is associated with dysregulation in the gut-liver-brain axis, which includes
        intestinal barrier dysfunction and gut microbial dysbiosis. However, despite current standard
        of care (SOC) therapy i.e., lactulose and rifaximin, there remains a subset of patients who
        continue to suffer recurrence, which leads to further cognitive impairment, sarcopenia and
        readmissions. There remain several factors that can influence the microbiota, such as
        demographics (geographic area, sex and diet), etiology, drugs, interventions, and ﬁnally the
        sampling compartment. These factors need to be controlled for and considered in the
        interpretation of future studies. The microbiome dynamic change during rehabilitation in
        cirrhotic patients with sarcopenia has never been studied and is worth exploring.
  
        Furthermore, from our previous study, the investigators have shown that one-year efficacy of
        rifaximin add-on to lactulose is superior to lactulose alone in patients with cirrhosis
        complicated with recurrent HE in Taiwan. The investigators also have preliminary data showing
        that rehabilitation could improve patient's sarcopenia. Further cohort validation is urgently
        required.
  
        Our innovative research purposes:
  
          1. To explore the changes of fecal microbiota before and after treatment such as resistance
             training rehabilitation as a reference for future fecal microbiota transplantation;
  
          2. To measure the changes of sarcopenia levels before and after rehabilitation
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Handgrip Strength
  time frame: 6 months
  description: Handgrip strength is an assessment of muscle strength. The cutoff value of the handgrip is < 30 kg in men and < 20 kg in women.
  measure: Short Physical Performance Battery (SPPB)
  time frame: 6 months
  description: Short Physical Performance Battery (SPPB) is an assessment of physical performance. The cut-off value of the Short Physical Performance Battery (SPPB) score for determining sarcopenia is ≤ 9.
  measure: Dual-energy X-ray absorptiometry (DEXA)
  time frame: 6 months
  description: Dual-energy X-ray absorptiometry (DXA) is the gold-standard technique in the analysis of body composition. The cut-off value of appendicular skeletal muscle mass (ASMI) score for determining sarcopenia is < 7.0 kg/m^2 in men and < 5.4 kg/m^2 in women.
  measure: Mini-Mental Status Examination (MMSE)
  time frame: 6 months
  description: Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. The cut-off value of Mini-Mental State Examination (MMSE) score is < 28.
  measure: Psychometric Hepatic Encephalopathy Score (PHES)
  time frame: 6 months
  description: The psychometric hepatic encephalopathy score (PHES) is the gold standard for diagnosing minimal hepatic encephalopathy (MHE). The cut-off value of the Psychometric Hepatic Encephalopathy Score (PHES) for determining minimal hepatic encephalopathy (MHE) is ≤ -4.
  measure: Animal Naming Test (ANT)
  time frame: 6 months
  description: The animal naming test (ANT) is an easy tool for the assessment of hepatic encephalopathy (HE). The cut-off value of the Animal Naming Test (ANT) score for determining hepatic encephalopathy (HE) is ≤ 19.
  measure: Blood cytokine levels [IL-6]
  time frame: 6 months
  description: Serum IL-6 level (pg/ mL)
  measure: Blood ammonia levels [NH3]
  time frame: 6 months
  description: Serum ammonia level (μg/dL)
  measure: Electroencephalogram (EEG)
  time frame: 6 months
  description: Quantified EEG spectral analysis:
  Grade 0: Mean dominant frequency (MDF)> 6.8 Hz and no theta nor delta wave Grade 1: MDF > 6.8Hz and theta wave relative power ≧35% Grade 2: MDF≤ 6.8 Hz and delta wave relative power<49% Grade 3: MDF≤ 6.8 Hz and delta wave relative power≧49%
  measure: Fecal Microbiota
  time frame: 6 months
  description: Check fecal microbiota taxonomy profile and relative abundance changes.
  arm group label: Rehabilitation Training
  arm group type: Experimental
  description: Rehabilitation Training is provided to patients with Liver Cirrhosis combined with sarcopenia.
  arm group label: No-Rehabilitation Training
  arm group type: No Intervention
  description: No extra training is provided to patients with Liver Cirrhosis combined with sarcopenia.
  intervention type: Behavioral
  intervention name: Rehabilitation Training
  description: 12 week Rehabilitation Training course
  arm group label: Rehabilitation Training
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: CHIEN-HAO HUANG
  role: Principal Investigator
  affiliation: Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
  last name: CHIEN-HAO HUANG, MD
  phone: +886 9753 66128
  email: q12248@cgmh.org.tw
  facility: 
  status: Recruiting
  contact: 
  country: Taiwan
  responsible party type: Sponsor
  mesh term: Hepatic Encephalopathy
  mesh term: Sarcopenia
  mesh term: Brain Diseases
  sharing ipd: No