Impact of Low Protein Diet Supplemented With Ketoanalogues Supplementation on Uremic Toxins Production

Renal Failure Clinical Trial

— KETO-GUT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03959228
• Other study ID #: 69HCL18_0957
• Status: Recruiting
• Phase: Phase 3
• Start date: November 12, 2019
• Est. completion date: December 12, 2023

Study information

• Verified date: July 2021
• Source: Hospices Civils de Lyon
• Contact: Laetitia KOPPE, MD
• Phone: +33 4 72 67 87 15
• Email: Laetitia.koppe[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 12, 2023
• Est. primary completion date: December 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Renal Failure
• Renal Insufficiency

Intervention

Drug:
• keto-analogs
The patients that will be included in the experimental arm will have additional keto-analogs (1 pill/5 kg).

Locations

Country	Name	City	State
France	Centre Hospitalier Lyon SUD	Pierre-Bénite

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

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