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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Drug: Renamezin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeongsangbuk-do
    • Gumi, Gyeongsangbuk-do, Korea, Republic of, 39295
      • CHA Gumi Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of dialysis initiation	If a patient requires dialysis initiation during study period, the date is recorded.	Through study completion, an average of 2 years
Rate of hospital admission	The rate of patients requiring in-patient care during the study participation is calculated.	Through study completion, an average of 2 years
Death rate	Death rate is calculated if any patients expire during participation.	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Gumi Cha Medical Center
• Investigators: Principal Investigator: Jun Chul Kim, MD, PhD, CHA Gumi Medical Center

Publications and helpful links

General Publications

• Lee SM, Han MY, Kim SH, Cha RH, Kang SH, Kim JC, An WS. Indoxyl Sulfate Might Play a Role in Sarcopenia, While Myostatin Is an Indicator of Muscle Mass in Patients with Chronic Kidney Disease: Analysis from the RECOVERY Study. Toxins (Basel). 2022 Sep 23;14(10). pii: 660. doi: 10.3390/toxins14100660.
• Shin J, Kim JC, Kim SH. Reply - Letter to the editor: Comment on "phase angle as a marker for muscle health and quality of life in patients with chronic kidney disease". Clin Nutr. 2022 Sep;41(9):2058. doi: 10.1016/j.clnu.2022.07.020. Epub 2022 Jul 21.
• Cha RH, Kang SH, Han MY, An WS, Kim SH, Kim JC. Effects of AST-120 on muscle health and quality of life in chronic kidney disease patients: results of RECOVERY study. J Cachexia Sarcopenia Muscle. 2022 Feb;13(1):397-408. doi: 10.1002/jcsm.12874. Epub 2021 Dec 3.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2018
• Primary Completion (Actual): July 14, 2020
• Study Completion (Actual): July 14, 2020

Study Registration Dates

• First Submitted: November 28, 2018
• First Submitted That Met QC Criteria: December 25, 2018
• First Posted (Actual): December 27, 2018

Study Record Updates

• Last Update Posted (Actual): December 17, 2020
• Last Update Submitted That Met QC Criteria: December 14, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Sarcopenia; AST-120; Indoxyl sulfate
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Neurologic Manifestations; Renal Insufficiency; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Kidney Diseases; Renal Insufficiency, Chronic; Sarcopenia
• Other Study ID Numbers: GM18-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No