Role of AST120 for Sarcopenia Prevention in Pre-dialysis Chronic Kidney Disease

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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RolE of AST120 in sarCOpenia preVEntion in pRe-dialYsis Chronic Kidney Disease Patients (RECOVERY): Prospective Open-label Randomized Controlled Multicenter Study

Conditions
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Chronic Kidney Diseases

Intervention / Treatment
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* Drug: Renamezin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult older than 19 years Pre-dialysis chronic kidney disease Serum creatinine level 2.0-5.0 mg/dL or MDRD or CKD-EPI eGFR 15-60 mL/min/1.73 m² Serum albumin ≥ 3.0 g/dL No previous use of oral absorbant during 4 weeks prior to screening No change of treatment for chronic kidney disease during 4 weeks prior to screening Written informed consent to participate in this clinical study Capable of independent physical activity, an assisted device use is acceptable Exclusion Criteria: Impaired GI peristalsis Uncontrolled constipation Prior renal transplant On immunosuppressant (small dose users may be accepted according to the PI's decision) GI ulcer or esophageal varix Uncontrolled hypertension (systolic BP ≥180 mmHg or diastolic BP ≥110 mmHg) History of admission for an acute cardiovascular incident within 3 months prior to screening Current acute infection state Liver function failure (ALT, AST over 2.5 times of normal reference range) Uncontrolled diabetes patient (HbA1c >10 % or fasting glucose >250 mg/dL) Malignancy (patients of post-remission 5 years without any recurrence can be enrolled, except for squamous cell carcinoma in situ) Pregnancy, on breastfeeding Not agreed to medical contraceptive use during participating in the study Concurrent participation in another clinical trial Drug or alcohol-dependent Other clinical trial medication administration more than once within 30 days prior to enrollment Expected dialysis or kidney transplantation within 3 months prior to enrollment Dependent physical activity Musculoskeletal disease that may debilitate functional independence Lower limb amputee not using a prosthesis Severe retinal disease (e.g., proliferative diabetic retinopathy, vitreous hemorrhage) Claudication Other patients inappropriate to participate by the PI's decision

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Renamezin (AST-120) group or non-Renamezin group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Renamezin<br>oral treatment duration: three times a day, 7 capsules (2g) once, for 48 weeks | Drug: Renamezin<br>* 7 capsules once, three times a day, for 48 weeks<br>* Other names: Renamezin administration;|
| No Intervention: Non-Renamezin<br>no use of Renamezin | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of 6 meter walking speed at 24 weeks | As a measure of physical performance, 6 meter walking test is used. Static start and dynamic start speed will be assessed twice each. | Change of baseline 6 meter walking speed at 24 weeks | 
| Change of 6 meter walking speed at 48 weeks | As a measure of physical performance, 6 meter walking test is used. Static start and dynamic start speed will be assessed twice each. | Change of baseline 6 meter walking speed at 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition test | Bioelectrical impedance analysis (using InBody S10) | Baseline, 24 week, 48 week | 
| Serum level of indoxyl sulfate, myostatin, Tumor Necrosis Factor-alpha, Interleukin-6 | Level of serum indoxyl sulfate, myostatin, TNF-alpha, and IL-6 will be obtained by laboratory blood test. | Baseline, 24 week, 48 week | 
| Serum level of creatinine and estimated Glomerular Filtration Rate (eGFR) | Level of serum creatinine, and eGFR (mL/min/1.73 m²) will be obtained by laboratory blood test. | Baseline, 24 week, 48 week | 
| Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF 1.3) | 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. | Baseline, 24 week, 48 week | 
| Charlson Co-morbidity Index | 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. | Baseline, 24 week, 48 week | 
| International Physical Activity Questionnaire Short Form | 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. | Baseline, 24 week, 48 week | 
| Grip strength | Using TAKEI handgrip strength dynamometer (TKK5401, Japan), grip strength while flexing elbow and extending elbow will be assessed. | Baseline, 24 week, 48 week | 
| 24h body activity measure | Using BAND2 model of InBody cooperation, activity amount of each participant is collected for 7 days. | Baseline, 24 week, 48 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcopenia, AST-120, Indoxyl sulfate