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FGF19 and Chronic Kidney Disease (RENAMUS 19)

Primary Purpose

Chronic Kidney Diseases

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Meal test and muscle biopsies
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Chronic Kidney Diseases

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

-For the patient population:

  • estimated GFR <60 ml / min / 1.73m2 according to the CKD-EPI formula OR patients dialyzed for more than 3 months
  • No history of kidney transplant
  • BMI between 18 and 30 kg / m²
  • For women of childbearing age, at least one method of contraception recognized as effective
  • Willing and able to give informed consent

For control group:

  • Potential living kidney donor
  • Willing and able to give informed consent

For all of the study participants:

o Non diabetic (fasting blood glucose <1.26 g / L, or absence of insulin or oral antidiabetic treatment)

Exclusion Criteria:

  • For the patient population:

    • Subjects with a history of colectomy, gut resection or cholecystectomy
    • Having received antibiotics, prebiotics, probiotics in the last 3 months.
    • Taking a high dose laxative treatment (> 2 doses per day) in the last 3 months
    • Hemoglobin <7 g / dl or <9 g / L in case of previous cardiovascular disease

  • For control group:

    • DFGe ≤ 80 ml / min / 1.73m2 according to CKD-EPI
    • High blood pressure (PA≥140 / 90 mmHg) or taking antihypertensive treatment
    • Presence of proteinuria (> 0.15 g / 24h) or micro-albuminuria (> 3 mg / mg creatinuria) or hematuria (> 20 GR / mm3)

  • For all of the study participants:

    • Hemoglobin <7 g / dl or <9 g / L in case of previous cardiovascular disease
    • Active inflammatory, infectious, cardiovascular or neoplastic disease
    • Period of exclusion from a previous study or already participating in a clinical research protocol having an impact on the study judgment criteria
    • Exposure to ionizing radiation (medical radiological examinations or occupational exposure with exposure greater than 20 mSv) in the 6 months preceding inclusion
    • No affiliation to social security
    • Patient under guardianship or safeguarding justice
    • Pregnant patient (a pregnancy test will be carried out for women of reproductive age o For the patients and control group will accept muscles biopsies
    • Presence of a precarious venous capital that does not allow the placement of a venous catheter - Thrombocytopenia
    • History of arrhythmias or cardiac conduction disorders
    • Taking anticoagulant and / or antiplatelet agent
    • Pulse <50 bpm
    • Allergy to local anesthetics and / or plaster

Sites / Locations

  • Centre Hospitalier Lyon SUDRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

CKD patients

Haemodialysis patients

Healthy volunteers

Arm Description

Patients with CKD, non-diabetic, without a history of renal transplantation, without digestive pathology, aged 18 to 70 and an estimate of the glomerular filtration rate (eGFR) <60 ml / min / 1.73m2 according to the formula of CKD-EPI.

Patients on hemodialysis, for more than 3 months, with no history of kidney transplantation, without digestive pathology, aged 18 to 70 with a BMI between 18 and 30 kg / m2

Healthy volunteers (controls) recruited from the population of living kidney donors

Outcomes

Primary Outcome Measures

Correlation between the fasting plasma concentration of FGF19 and the muscle mass
Study the correlation between the fasting plasma concentration of FGF19 and the muscle mass in % of body weight, measured by DEXA scanner (Dual-X-Ray-Absorptiometry) in non-dialyzed MRC patients with a measured glomerular filtration rate (mDFG) <60 ml / min /1.73m², hemodialysis patients and healthy voluntary being assessed for a kidney donation.

Secondary Outcome Measures

Correlation between fasting plasma FGF19 concentration and Glomerular Filtration Rate (GFR)
Correlation between fasting plasma FGF19 concentration and Glomerular Filtration Rate (GFR) measured by a reference method (Iohexol clearance or Tc DTPA) for non-dialysis patients (in ml/min/1.73m2)
Correlation between fasting plasma FGF19 concentration and muscle strength
Correlation between fasting plasma FGF19 concentration and muscle strength in kilograms in the Hand Grip
Correlation between fasting plasma FGF19 concentration and muscle performance
Correlation between fasting plasma FGF19 concentration and muscle performance assessed by the 6-minute walk test (TM6) evaluated in metres and by the SPPB (Short Physical Performance Battery) test with a score between 0 and 12
Correlation between fasting plasma FGF19 concentration and muscle quality
Correlation between fasting plasma FGF19 concentration and muscle quality assessed by ultrasound (echogenicity intensity (EI) from 0 for black to 255 white and qualitatively by the Heckmatt visual assessment scale (Grade I to IV)).
Correlation between fasting plasma FGF19 concentration and muscle mass
Correlation between fasting plasma FGF19 concentration and muscle mass obtained by ultrasound by measuring the cross-sectional area (in mm2) of the rectus femoris muscle (RF-CSA, Rectus femoris anatomical cross-sectional area)
Correlation between fasting plasma FGF19 concentration and bone density
Correlation between fasting plasma FGF19 concentration and bone density determined by DEXA scan (total T-score)
Correlation between fasting plasma FGF19 concentration and bone quality in dialysis patients
Correlation between fasting plasma FGF19 concentration and bone quality in dialysis patients as assessed by the level of bone remodelling determined on bone biopsy (BFR/BS)
Correlation between fasting plasma FGF19 concentration and physical activity
Correlation between fasting plasma FGF19 concentration and physical activity assessed by the STAQ questionnaire (in hours/week) only if the primary endpoint is significant.
Correlation between fasting plasma FGF19 concentration and faecal bacterial microbiological profile
Correlation between fasting plasma FGF19 concentration and faecal bacterial microbiological profile by 16s sequencing of stool samples (analysis performed in a second step)
Correlation between fasting plasma FGF19 concentration and the number of adverse events
Correlation between fasting plasma FGF19 concentration and the number of adverse events such as mortality, cardiovascular events and fractures throughout the protocol

Full Information

First Posted
March 19, 2021
Last Updated
September 26, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT04896047
Brief Title
FGF19 and Chronic Kidney Disease
Acronym
RENAMUS 19
Official Title
Role of FGF19 in Sarcopenia Associated With Chronic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2022 (Actual)
Primary Completion Date
February 6, 2027 (Anticipated)
Study Completion Date
February 6, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Sarcopenia in chronic kidney disease (CKD) affects 50% of dialysis patients and 20% of patients with non-dialyzed CKD and reduce quality of life and survival. The pathophysiology of uremic sarcopenia is multifactorial (accumulation of toxins, metabolic disturbances, etc.) and poorly characterized. These pejorative factors are associated with malnutrition and a sedentary lifestyle. Currently, there are no strategies to combat sarcopenia with the exception of physical activity, which is only possible for a limited number of patients due to their comorbidities. Developing new pharmacological strategies to combat sarcopenia is necessary. FGF19 is a growth factor produced in the ileum involved in metabolic homeostasis. In the laboratory, a new function of FGF19 has been discovered. FGF19 acts as a hormonal factor stimulating muscle mass and strength. Preliminary studies had shown a decrease in the concentration and secretion of FGF19 in response to a meal in haemodialysis patients. However, the link between FGF19, muscle mass and CKD has never been demonstrated. The aim of this study is to assess the relationship between the concentration and secretion of FGF19 and muscle function in a large population of patients with CKD of different stages. Given the hormonal communication between the bone and the muscle, the investigators will also recover the bone histological parameters from a bone biopsy if dialysis patients are to benefit from this as part of their follow-up. The investigators hypothesize that a decrease in FGF19 concentration and secretion in CKD is associated with a decrease in muscle mass and strength.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
170 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CKD patients
Arm Type
Experimental
Arm Description
Patients with CKD, non-diabetic, without a history of renal transplantation, without digestive pathology, aged 18 to 70 and an estimate of the glomerular filtration rate (eGFR) <60 ml / min / 1.73m2 according to the formula of CKD-EPI.
Arm Title
Haemodialysis patients
Arm Type
Active Comparator
Arm Description
Patients on hemodialysis, for more than 3 months, with no history of kidney transplantation, without digestive pathology, aged 18 to 70 with a BMI between 18 and 30 kg / m2
Arm Title
Healthy volunteers
Arm Type
Active Comparator
Arm Description
Healthy volunteers (controls) recruited from the population of living kidney donors
Intervention Type
Procedure
Intervention Name(s)
Meal test and muscle biopsies
Intervention Description
The FGF19 parameters will be assessed in fasting and in postprandial period after the consumption of a hyper-carbohydrate and hyper-lipidic test meal called Flexmeal. A muscle biopsies by a needle will be performed before and after the Flexmeal.
Primary Outcome Measure Information:
Title
Correlation between the fasting plasma concentration of FGF19 and the muscle mass
Description
Study the correlation between the fasting plasma concentration of FGF19 and the muscle mass in % of body weight, measured by DEXA scanner (Dual-X-Ray-Absorptiometry) in non-dialyzed MRC patients with a measured glomerular filtration rate (mDFG) <60 ml / min /1.73m², hemodialysis patients and healthy voluntary being assessed for a kidney donation.
Time Frame
At the end of the study (55 months)
Secondary Outcome Measure Information:
Title
Correlation between fasting plasma FGF19 concentration and Glomerular Filtration Rate (GFR)
Description
Correlation between fasting plasma FGF19 concentration and Glomerular Filtration Rate (GFR) measured by a reference method (Iohexol clearance or Tc DTPA) for non-dialysis patients (in ml/min/1.73m2)
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and muscle strength
Description
Correlation between fasting plasma FGF19 concentration and muscle strength in kilograms in the Hand Grip
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and muscle performance
Description
Correlation between fasting plasma FGF19 concentration and muscle performance assessed by the 6-minute walk test (TM6) evaluated in metres and by the SPPB (Short Physical Performance Battery) test with a score between 0 and 12
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and muscle quality
Description
Correlation between fasting plasma FGF19 concentration and muscle quality assessed by ultrasound (echogenicity intensity (EI) from 0 for black to 255 white and qualitatively by the Heckmatt visual assessment scale (Grade I to IV)).
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and muscle mass
Description
Correlation between fasting plasma FGF19 concentration and muscle mass obtained by ultrasound by measuring the cross-sectional area (in mm2) of the rectus femoris muscle (RF-CSA, Rectus femoris anatomical cross-sectional area)
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and bone density
Description
Correlation between fasting plasma FGF19 concentration and bone density determined by DEXA scan (total T-score)
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and bone quality in dialysis patients
Description
Correlation between fasting plasma FGF19 concentration and bone quality in dialysis patients as assessed by the level of bone remodelling determined on bone biopsy (BFR/BS)
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and physical activity
Description
Correlation between fasting plasma FGF19 concentration and physical activity assessed by the STAQ questionnaire (in hours/week) only if the primary endpoint is significant.
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and faecal bacterial microbiological profile
Description
Correlation between fasting plasma FGF19 concentration and faecal bacterial microbiological profile by 16s sequencing of stool samples (analysis performed in a second step)
Time Frame
At the end of the study (55 months)
Title
Correlation between fasting plasma FGF19 concentration and the number of adverse events
Description
Correlation between fasting plasma FGF19 concentration and the number of adverse events such as mortality, cardiovascular events and fractures throughout the protocol
Time Frame
At the end of the study (55 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: -For the patient population: estimated GFR <60 ml / min / 1.73m2 according to the CKD-EPI formula OR patients dialyzed for more than 3 months No history of kidney transplant BMI between 18 and 30 kg / m² For women of childbearing age, at least one method of contraception recognized as effective Willing and able to give informed consent For control group: Potential living kidney donor Willing and able to give informed consent For all of the study participants: o Non diabetic (fasting blood glucose <1.26 g / L, or absence of insulin or oral antidiabetic treatment) Exclusion Criteria: For the patient population: Subjects with a history of colectomy, gut resection or cholecystectomy Having received antibiotics, prebiotics, probiotics in the last 3 months. Taking a high dose laxative treatment (> 2 doses per day) in the last 3 months Hemoglobin <7 g / dl or <9 g / L in case of previous cardiovascular disease For control group: DFGe ≤ 80 ml / min / 1.73m2 according to CKD-EPI High blood pressure (PA≥140 / 90 mmHg) or taking antihypertensive treatment Presence of proteinuria (> 0.15 g / 24h) or micro-albuminuria (> 3 mg / mg creatinuria) or hematuria (> 20 GR / mm3) For all of the study participants: Hemoglobin <7 g / dl or <9 g / L in case of previous cardiovascular disease Active inflammatory, infectious, cardiovascular or neoplastic disease Period of exclusion from a previous study or already participating in a clinical research protocol having an impact on the study judgment criteria Exposure to ionizing radiation (medical radiological examinations or occupational exposure with exposure greater than 20 mSv) in the 6 months preceding inclusion No affiliation to social security Patient under guardianship or safeguarding justice Pregnant patient (a pregnancy test will be carried out for women of reproductive age o For the patients and control group will accept muscles biopsies Presence of a precarious venous capital that does not allow the placement of a venous catheter - Thrombocytopenia History of arrhythmias or cardiac conduction disorders Taking anticoagulant and / or antiplatelet agent Pulse <50 bpm Allergy to local anesthetics and / or plaster
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laetitia KOPPE, MD
Phone
+33 4 72 67 87 15
Email
laetitia.koppe@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Cécile BARNEL
Phone
+33 4 78 86 37 12
Email
cecile.barnel@chu-lyon.fr
Facility Information:
Facility Name
Centre Hospitalier Lyon SUD
City
Pierre-Bénite
ZIP/Postal Code
69310
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laetitia KOPPE, PhD
Phone
04 72 67 87 15
Ext
+33
Email
laetitia.koppe@chu-lyon.fr

12. IPD Sharing Statement

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FGF19 and Chronic Kidney Disease

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