Impact of Low Protein Diet Supplemented With Ketoanalogues Supplementation on Uremic Toxins Production (KETO-GUT)

Impact of Low Protein Diet Supplemented With Ketoanalogues on Uremic Toxins Production and Glucose Metabolism in Chronic Kidney Disease

Chronic kidney disease (CKD) is associated with accumulation of uremic toxins like p-cresyl sulfate and indoxyl sulfate that are associated of cardiovascular complication and perturbation of glucose metabolism. These toxins are produced by fermentation of protein by intestinal microbiota but the role of low protein diet and ketoanalogue supplementation on uremic toxins production and microbiota composition are unknown. Low protein diet supplemented with ketoanalogues is recommended inCKD patients to prevent progression of renal disease. The aim of this study is to determine the impact of uremic toxins concentration, microbiota composition and gut hormone involved in carbohydrate metabolism ( GLP-1, FGF19, bile acids) with low protein diet supplemented with ketoanalogues.

Study Overview

• Status: Recruiting
• Conditions: Renal Failure
• Intervention / Treatment: Drug: keto-analogs

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Laetitia KOPPE, MD; Phone Number: +33 +33 4 72 67 87 15; Email: Laetitia.koppe@chu-lyon.fr

Study Locations

• France
  • Pierre-Bénite, France, 69310
    • Recruiting
    • Centre Hospitalier LYON SUD
    • Sub-Investigator: Denis FOUQUE, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CKD stage 4-5 with estimated glomerular filtration rate < 30 ml/min/1,73m2
• No dialysis
• No history of kidney transplantation
• Non-diabetic (fasting glucose <1.26 g / L, or no insulin or oral antidiabetic therapy)
• BMI between 18 and 30 kg / m2
• Patient followed in the nephrology department of Professor FOUQUE at the Lyon Sud hospital
• For women of childbearing age, at least one method of contraception recognized as effective
• Patient who gave consent to open participation and signed the consent to participate in the study

Exclusion Criteria:

• Patient with progressive inflammatory, infectious, cardiovascular or neoplastic disease
• Patient refusing a dietary follow-up
• Patient having a planned transplant or dialysis project in the next 6 months.
• Patient having a colectomy, resection of the small intestine or cholecystectomy
• Patient who has received antibiotics, prebiotics, probiotics in the last 3 months.
• Patient treated with more than 2 g of calcium per day
• Patient using laxatives (more than 2 per day)
• Patient having:
• Uncontrolled metabolic acidosis (bicarbonatemia <18 mM)
• Hyperparathyroidism (PTH greater than 5 times the upper limit of normal)
• Hypercalcemia (Calcium> 2.55 mmol / L) or hypophosphoremia <0.70 mmol / L
• Anemia (hemoglobinemia <80g / L)
• Undernutrition criteria: albumin <38 g / L or prealbumin <0.3 g / L
• Known hypersensitivity to any of the substances or excipients of Ketosteril
• Subject in exclusion period of a previous study
• Patient not affiliated to social security
• Patient under guardianship or in the interests of justice
• Patient who is pregnant, breastfeeding or likely to become pregnant during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: referencial diet; 0.8 g/kg/day of protein
Experimental: protein very poor diet with additional keto-analogs; 0.4 g/kg/day of protein and 1 pill of Ketosteril/ 5kg.	Drug: keto-analogs; The patients that will be included in the experimental arm will have additional keto-analogs (1 pill/5 kg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indoxyl Sulfate Plasmatic concentration	Concentration mesure of Indoxyl Sulfate Plasmatic	After 3 months of diet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMAO uremic toxin concentraction ( TMAO, PCS) in plasma	concentration mesure of uremic toxin in plasma	After 3 months
TMAO uremic toxin concentraction in urine ( IS, PCS)	concentration mesure of uremic toxin in urine	After 3 months
Composition of intestinal microbiota	sequencing 16s stool samples	Before three months
Composition of intestinal microbiota	sequencing 16s stool samples	After three months
Insulin sensitivity	oral glucose tolerance test	After 3 months
Insulin secretion	oral glucose tolerance test	After 3 months
Secretion of gut hormone like GLP-1 and FGF19	oral glucose tolerance test	After 3 months
Composition of bile acid	composition of bile acid mesure by chromatography	After 3 months
Concentration of bile acid	concentration of bile acid mesure by Chromatography	After 3 months
Concentration of endotoxinemia (LPS)	LPS concentration mesure	After 3 months
Nutritional status	Nutrional status will be determined with body weight, body composition with bioimpedecemetry, albumin, prealbumin, muscle status with hand grip.	After 3 months
Calcemia	calcemia mesure	After 3 months
Observance of diet	counting of returned ketosteril tablets	After 3 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2019
• Primary Completion (Anticipated): December 12, 2023
• Study Completion (Anticipated): December 12, 2023

Study Registration Dates

• First Submitted: April 25, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 69HCL18_0957

Drug and device information, study documents

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