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

Phase 3

• Conditions: Renal Failure
• Interventions: Drug: keto-analogs

• Registration Number: NCT03959228
• Lead Sponsor: Hospices Civils de Lyon

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-25
• Study First Submitted QC: 2019-05-20
• Study First Posted: 2019-05-22
• Study Start: 2019-11-12
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-05
• Last Update Posted: 2021-07-09
• Primary Completion: 2023-12-12
• Study Completion: 2023-12-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
protein very poor diet with additional keto-analogs	keto-analogs	0.4 g/kg/day of protein and 1 pill of Ketosteril/ 5kg.

Primary Outcome Measures

Name	Time	Method
Indoxyl Sulfate Plasmatic concentration	After 3 months of diet	Concentration mesure of Indoxyl Sulfate Plasmatic

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Centre Hospitalier Lyon SUD; 🇫🇷 Pierre-Bénite, France