<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/NCT03788252</url>
  </required_header>
  <id_info>
    <org_study_id>GM18-11</org_study_id>
    <nct_id>NCT03788252</nct_id>
  </id_info>
  <brief_title>Role of AST120 for Sarcopenia Prevention in Pre-dialysis Chronic Kidney Disease</brief_title>
  <acronym>RECOVERY</acronym>
  <official_title>RolE of AST120 in sarCOpenia preVEntion in pRe-dialYsis Chronic Kidney Disease Patients (RECOVERY): Prospective Open-label Randomized Controlled Multicenter Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gumi Cha Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gumi Cha Medical Center</source>
  <oversight_info>
    <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 is to assess the effect of 48 weeks administration of Renamezin capsule on&#xD;
      prevention of sarcopenia in pre-dialysis patients with chronic kidney disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Skeletal muscle atrophy, referred to as sarcopenia, and impaired physical performance are&#xD;
      accompanied in chronic kidney disease patients during disease progression. Decreased physical&#xD;
      performance derived from sarcopenia precipitates poor prognostic influence in the clinical&#xD;
      outcome, as reported in previous studies showing correlations between poor physical&#xD;
      performance, poor quality of life, poor renal prognosis, and mortality. Therefore,&#xD;
      maintaining physical performance is mandatory to improve the prognosis of chronic kidney&#xD;
      disease patients.&#xD;
&#xD;
      AST-120 is an oral absorbent capsule designed to remove circulating indoxyl sulfate, a uremic&#xD;
      toxin. As indoxyl sulfate is reported to cause mitochondrial dysfunction in skeletal muscle,&#xD;
      AST-120 contributes to the recovery of mitochondrial function by reducing indoxyl sulfate. In&#xD;
      addition, AST-120 is reported to delay the initiation of dialysis and the decrease of&#xD;
      glomerular filtration rate and the increase of serum creatinine level. However, the effect of&#xD;
      AST-120 on sarcopenia in pre-dialysis patients have not been reported. This study is to&#xD;
      investigate the effect of AST-120 on sarcopenia prevention in pre-dialysis chronic kidney&#xD;
      disease patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 23, 2018</start_date>
  <completion_date type="Actual">July 14, 2020</completion_date>
  <primary_completion_date type="Actual">July 14, 2020</primary_completion_date>
  <phase>Phase 4</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>Renamezin (AST-120) group or non-Renamezin group</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of 6 meter walking speed at 24 weeks</measure>
    <time_frame>Change of baseline 6 meter walking speed at 24 weeks</time_frame>
    <description>As a measure of physical performance, 6 meter walking test is used. Static start and dynamic start speed will be assessed twice each.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of 6 meter walking speed at 48 weeks</measure>
    <time_frame>Change of baseline 6 meter walking speed at 48 weeks</time_frame>
    <description>As a measure of physical performance, 6 meter walking test is used. Static start and dynamic start speed will be assessed twice each.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body composition test</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Bioelectrical impedance analysis (using InBody S10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum level of indoxyl sulfate, myostatin, Tumor Necrosis Factor-alpha, Interleukin-6</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Level of serum indoxyl sulfate, myostatin, TNF-alpha, and IL-6 will be obtained by laboratory blood test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum level of creatinine and estimated Glomerular Filtration Rate (eGFR)</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Level of serum creatinine, and eGFR (mL/min/1.73 m²) will be obtained by laboratory blood test.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF 1.3)</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Health-related quality of life (HRQOL) is assessed via KDQOL-SF 1.3. KDQOL-SF 1.3 is validated questionnaires to assess HRQOL. HRQOL consists of three subscales; physical health, mental health, and kidney disease health. The summation of subscales ranges between 0 - 100, and the higher values indicate the better HRQOL status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Charlson Co-morbidity Index</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Charlson Co-morbidity Index is used to assess underlying co-morbidity of each patient. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use. Age weighting is added to total comorbidity score in a score of zero to four.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International Physical Activity Questionnaire Short Form</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>International Physical Activity Questionnaire (IPAQ) Short Form is used to assess the amount of time spent for daily physical activity. IPAQ Short Form comprises of 7 questionnaires of activities which asks to report time spent for each activity during last week.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grip strength</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Using TAKEI handgrip strength dynamometer (TKK5401, Japan), grip strength while flexing elbow and extending elbow will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>24h body activity measure</measure>
    <time_frame>Baseline, 24 week, 48 week</time_frame>
    <description>Using BAND2 model of InBody cooperation, activity amount of each participant is collected for 7 days.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Time of dialysis initiation</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>If a patient requires dialysis initiation during study period, the date is recorded.</description>
  </other_outcome>
  <other_outcome>
    <measure>Rate of hospital admission</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>The rate of patients requiring in-patient care during the study participation is calculated.</description>
  </other_outcome>
  <other_outcome>
    <measure>Death rate</measure>
    <time_frame>Through study completion, an average of 2 years</time_frame>
    <description>Death rate is calculated if any patients expire during participation.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">150</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <arm_group>
    <arm_group_label>Renamezin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>oral treatment duration: three times a day, 7 capsules (2g) once, for 48 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Renamezin</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>no use of Renamezin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Renamezin</intervention_name>
    <description>7 capsules once, three times a day, for 48 weeks</description>
    <arm_group_label>Renamezin</arm_group_label>
    <other_name>Renamezin administration</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult older than 19 years&#xD;
&#xD;
          -  Pre-dialysis chronic kidney disease&#xD;
&#xD;
          -  Serum creatinine level 2.0-5.0 mg/dL or MDRD or CKD-EPI eGFR 15-60 mL/min/1.73 m²&#xD;
&#xD;
          -  Serum albumin ≥ 3.0 g/dL&#xD;
&#xD;
          -  No previous use of oral absorbant during 4 weeks prior to screening&#xD;
&#xD;
          -  No change of treatment for chronic kidney disease during 4 weeks prior to screening&#xD;
&#xD;
          -  Written informed consent to participate in this clinical study&#xD;
&#xD;
          -  Capable of independent physical activity, an assisted device use is acceptable&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Impaired GI peristalsis&#xD;
&#xD;
          -  Uncontrolled constipation&#xD;
&#xD;
          -  Prior renal transplant&#xD;
&#xD;
          -  On immunosuppressant (small dose users may be accepted according to the PI's decision)&#xD;
&#xD;
          -  GI ulcer or esophageal varix&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic BP ≥180 mmHg or diastolic BP ≥110 mmHg)&#xD;
&#xD;
          -  History of admission for an acute cardiovascular incident within 3 months prior to&#xD;
             screening&#xD;
&#xD;
          -  Current acute infection state&#xD;
&#xD;
          -  Liver function failure (ALT, AST over 2.5 times of normal reference range)&#xD;
&#xD;
          -  Uncontrolled diabetes patient (HbA1c &gt;10 % or fasting glucose &gt;250 mg/dL)&#xD;
&#xD;
          -  Malignancy (patients of post-remission 5 years without any recurrence can be enrolled,&#xD;
             except for squamous cell carcinoma in situ)&#xD;
&#xD;
          -  Pregnancy, on breastfeeding&#xD;
&#xD;
          -  Not agreed to medical contraceptive use during participating in the study&#xD;
&#xD;
          -  Concurrent participation in another clinical trial&#xD;
&#xD;
          -  Drug or alcohol-dependent&#xD;
&#xD;
          -  Other clinical trial medication administration more than once within 30 days prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Expected dialysis or kidney transplantation within 3 months prior to enrollment&#xD;
&#xD;
          -  Dependent physical activity&#xD;
&#xD;
          -  Musculoskeletal disease that may debilitate functional independence&#xD;
&#xD;
          -  Lower limb amputee not using a prosthesis&#xD;
&#xD;
          -  Severe retinal disease (e.g., proliferative diabetic retinopathy, vitreous hemorrhage)&#xD;
&#xD;
          -  Claudication&#xD;
&#xD;
          -  Other patients inappropriate to participate by the PI's decision&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jun Chul Kim, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHA Gumi Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHA Gumi Medical Center</name>
      <address>
        <city>Gumi</city>
        <state>Gyeongsangbuk-do</state>
        <zip>39295</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>December 25, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 27, 2018</study_first_posted>
  <last_update_submitted>December 14, 2020</last_update_submitted>
  <last_update_submitted_qc>December 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Gumi Cha Medical Center</investigator_affiliation>
    <investigator_full_name>Jun Chul Kim</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Sarcopenia</keyword>
  <keyword>AST-120</keyword>
  <keyword>Indoxyl sulfate</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcopenia</mesh_term>
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>March 10, 2021</submitted>
    <returned>April 2, 2021</returned>
  </pending_results>
  <!-- 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/NCT03788252
org study id: GM18-11
nct id: NCT03788252
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is to assess the effect of 48 weeks administration of Renamezin capsule on
      prevention of sarcopenia in pre-dialysis patients with chronic kidney disease.
Skeletal muscle atrophy, referred to as sarcopenia, and impaired physical performance are
      accompanied in chronic kidney disease patients during disease progression. Decreased physical
      performance derived from sarcopenia precipitates poor prognostic influence in the clinical
      outcome, as reported in previous studies showing correlations between poor physical
      performance, poor quality of life, poor renal prognosis, and mortality. Therefore,
      maintaining physical performance is mandatory to improve the prognosis of chronic kidney
      disease patients.

      AST-120 is an oral absorbent capsule designed to remove circulating indoxyl sulfate, a uremic
      toxin. As indoxyl sulfate is reported to cause mitochondrial dysfunction in skeletal muscle,
      AST-120 contributes to the recovery of mitochondrial function by reducing indoxyl sulfate. In
      addition, AST-120 is reported to delay the initiation of dialysis and the decrease of
      glomerular filtration rate and the increase of serum creatinine level. However, the effect of
      AST-120 on sarcopenia in pre-dialysis patients have not been reported. This study is to
      investigate the effect of AST-120 on sarcopenia prevention in pre-dialysis chronic kidney
      disease patients.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Renamezin (AST-120) group or non-Renamezin group
primary purpose: Prevention
masking: None (Open Label)
measure: Change of 6 meter walking speed at 24 weeks
time frame: Change of baseline 6 meter walking speed at 24 weeks
description: As a measure of physical performance, 6 meter walking test is used. Static start and dynamic start speed will be assessed twice each.
measure: Change of 6 meter walking speed at 48 weeks
time frame: Change of baseline 6 meter walking speed at 48 weeks
description: As a measure of physical performance, 6 meter walking test is used. Static start and dynamic start speed will be assessed twice each.
measure: Body composition test
time frame: Baseline, 24 week, 48 week
description: Bioelectrical impedance analysis (using InBody S10)
measure: Serum level of indoxyl sulfate, myostatin, Tumor Necrosis Factor-alpha, Interleukin-6
time frame: Baseline, 24 week, 48 week
description: Level of serum indoxyl sulfate, myostatin, TNF-alpha, and IL-6 will be obtained by laboratory blood test.
measure: Serum level of creatinine and estimated Glomerular Filtration Rate (eGFR)
time frame: Baseline, 24 week, 48 week
description: Level of serum creatinine, and eGFR (mL/min/1.73 m²) will be obtained by laboratory blood test.
measure: Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF 1.3)
time frame: Baseline, 24 week, 48 week
description: Health-related quality of life (HRQOL) is assessed via KDQOL-SF 1.3. KDQOL-SF 1.3 is validated questionnaires to assess HRQOL. HRQOL consists of three subscales; physical health, mental health, and kidney disease health. The summation of subscales ranges between 0 - 100, and the higher values indicate the better HRQOL status.
measure: Charlson Co-morbidity Index
time frame: Baseline, 24 week, 48 week
description: Charlson Co-morbidity Index is used to assess underlying co-morbidity of each patient. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use. Age weighting is added to total comorbidity score in a score of zero to four.
measure: International Physical Activity Questionnaire Short Form
time frame: Baseline, 24 week, 48 week
description: International Physical Activity Questionnaire (IPAQ) Short Form is used to assess the amount of time spent for daily physical activity. IPAQ Short Form comprises of 7 questionnaires of activities which asks to report time spent for each activity during last week.
measure: Grip strength
time frame: Baseline, 24 week, 48 week
description: Using TAKEI handgrip strength dynamometer (TKK5401, Japan), grip strength while flexing elbow and extending elbow will be assessed.
measure: 24h body activity measure
time frame: Baseline, 24 week, 48 week
description: Using BAND2 model of InBody cooperation, activity amount of each participant is collected for 7 days.
measure: Time of dialysis initiation
time frame: Through study completion, an average of 2 years
description: If a patient requires dialysis initiation during study period, the date is recorded.
measure: Rate of hospital admission
time frame: Through study completion, an average of 2 years
description: The rate of patients requiring in-patient care during the study participation is calculated.
measure: Death rate
time frame: Through study completion, an average of 2 years
description: Death rate is calculated if any patients expire during participation.
arm group label: Renamezin
arm group type: Active Comparator
description: oral treatment duration: three times a day, 7 capsules (2g) once, for 48 weeks
arm group label: Non-Renamezin
arm group type: No Intervention
description: no use of Renamezin
intervention type: Drug
intervention name: Renamezin
description: 7 capsules once, three times a day, for 48 weeks
arm group label: Renamezin
other name: Renamezin administration
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Chul Kim, MD, PhD
role: Principal Investigator
affiliation: CHA Gumi Medical Center
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Gumi Cha Medical Center
investigator full name: Jun Chul Kim
investigator title: Professor
mesh term: Sarcopenia
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: Undecided
submitted: March 10, 2021
returned: April 2, 2021