Clinical trial NCT03788252: Role of AST120 for Sarcopenia Prevention in Pre-dialysis Chronic Kidney Disease
Official title: RolE of AST120 in sarCOpenia preVEntion in pRe-dialYsis Chronic Kidney Disease Patients (RECOVERY): Prospective Open-label Randomized Controlled Multicenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Kidney Diseases
Keywords: Sarcopenia
AST-120
Indoxyl sulfate
Lead sponsor: Gumi Cha Medical Center
Sponsor class: OTHER
First posted: 2018-12-27
Enrollment: 150
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Renamezin (AST-120) group or non-Renamezin group
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change of 6 meter walking speed at 24 weeks
timeFrame: Change of baseline 6 meter walking speed at 24 weeks
measure: Change of 6 meter walking speed at 48 weeks
timeFrame: Change of baseline 6 meter walking speed at 48 weeks
Secondary outcomes:
measure: Body composition test
timeFrame: Baseline, 24 week, 48 week
measure: Serum level of indoxyl sulfate, myostatin, Tumor Necrosis Factor-alpha, Interleukin-6
timeFrame: Baseline, 24 week, 48 week
measure: Serum level of creatinine and estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline, 24 week, 48 week
measure: Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF 1.3)
timeFrame: Baseline, 24 week, 48 week
measure: Charlson Co-morbidity Index
timeFrame: Baseline, 24 week, 48 week
measure: International Physical Activity Questionnaire Short Form
timeFrame: Baseline, 24 week, 48 week
measure: Grip strength
timeFrame: Baseline, 24 week, 48 week
measure: 24h body activity measure
timeFrame: Baseline, 24 week, 48 week
Other outcomes:
measure: Time of dialysis initiation
timeFrame: Through study completion, an average of 2 years
measure: Rate of hospital admission
timeFrame: Through study completion, an average of 2 years
measure: Death rate
timeFrame: Through study completion, an average of 2 years
Locations:
city: Gumi
country: Korea, Republic of
facility: CHA Gumi Medical Center
state: Gyeongsangbuk-do
Study officials:
affiliation: CHA Gumi Medical Center
name: Jun Chul Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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):660. doi: 10.3390/toxins14100660.
citation: 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. No abstract available.
citation: 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.