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

Primary Purpose

Chronic Kidney Diseases

Status

Completed

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

Renamezin

About this trial

This is an interventional prevention trial for Chronic Kidney Diseases focused on measuring Sarcopenia, AST-120, Indoxyl sulfate

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

CHA Gumi Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Renamezin

Non-Renamezin

Arm Description

oral treatment duration: three times a day, 7 capsules (2g) once, for 48 weeks

no use of Renamezin

Outcomes

Primary Outcome Measures

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 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.

Secondary Outcome Measures

Body composition test

Bioelectrical impedance analysis (using InBody S10)

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.

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.

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.

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.

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.

Grip strength

Using TAKEI handgrip strength dynamometer (TKK5401, Japan), grip strength while flexing elbow and extending elbow will be assessed.

24h body activity measure

Using BAND2 model of InBody cooperation, activity amount of each participant is collected for 7 days.

Full Information

NCT ID

NCT03788252

First Posted

November 28, 2018

Last Updated

December 14, 2020

Sponsor

Gumi Cha Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT03788252

Brief Title

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

Acronym

RECOVERY

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

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

November 23, 2018 (Actual)

Primary Completion Date

July 14, 2020 (Actual)

Study Completion Date

July 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Gumi Cha Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Diseases

Keywords

Sarcopenia, AST-120, Indoxyl sulfate

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

Renamezin (AST-120) group or non-Renamezin group

Masking

None (Open Label)

Allocation

Randomized

Enrollment

150 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Renamezin

Arm Type

Active Comparator

Arm Description

oral treatment duration: three times a day, 7 capsules (2g) once, for 48 weeks

Arm Title

Non-Renamezin

Arm Type

No Intervention

Arm Description

no use of Renamezin

Intervention Type

Drug

Intervention Name(s)

Renamezin

Other Intervention Name(s)

Renamezin administration

Intervention Description

7 capsules once, three times a day, for 48 weeks

Primary Outcome Measure Information:

Title

Change of 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.

Time Frame

Change of baseline 6 meter walking speed at 24 weeks

Title

Change of 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.

Time Frame

Change of baseline 6 meter walking speed at 48 weeks

Secondary Outcome Measure Information:

Title

Body composition test

Description

Bioelectrical impedance analysis (using InBody S10)

Time Frame

Baseline, 24 week, 48 week

Title

Serum level of indoxyl sulfate, myostatin, Tumor Necrosis Factor-alpha, Interleukin-6

Description

Level of serum indoxyl sulfate, myostatin, TNF-alpha, and IL-6 will be obtained by laboratory blood test.

Time Frame

Baseline, 24 week, 48 week

Title

Serum level of creatinine and estimated Glomerular Filtration Rate (eGFR)

Description

Level of serum creatinine, and eGFR (mL/min/1.73 m²) will be obtained by laboratory blood test.

Time Frame

Baseline, 24 week, 48 week

Title

Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF 1.3)

Description

Time Frame

Baseline, 24 week, 48 week

Title

Charlson Co-morbidity Index

Description

Time Frame

Baseline, 24 week, 48 week

Title

International Physical Activity Questionnaire Short Form

Description

Time Frame

Baseline, 24 week, 48 week

Title

Grip strength

Description

Using TAKEI handgrip strength dynamometer (TKK5401, Japan), grip strength while flexing elbow and extending elbow will be assessed.

Time Frame

Baseline, 24 week, 48 week

Title

24h body activity measure

Description

Using BAND2 model of InBody cooperation, activity amount of each participant is collected for 7 days.

Time Frame

Baseline, 24 week, 48 week

Other Pre-specified Outcome Measures:

Title

Time of dialysis initiation

Description

If a patient requires dialysis initiation during study period, the date is recorded.

Time Frame

Through study completion, an average of 2 years

Title

Rate of hospital admission

Description

The rate of patients requiring in-patient care during the study participation is calculated.

Time Frame

Through study completion, an average of 2 years

Title

Death rate

Description

Death rate is calculated if any patients expire during participation.

Time Frame

Through study completion, an average of 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jun Chul Kim, MD, PhD

Organizational Affiliation

CHA Gumi Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

CHA Gumi Medical Center

City

Gumi

State/Province

Gyeongsangbuk-do

ZIP/Postal Code

39295

Country

Korea, Republic of

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

36287929

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.

Results Reference

derived

PubMed Identifier

35963741

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.

Results Reference

derived

PubMed Identifier

34862753

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.

Results Reference

derived

Learn more about this trial

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

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