Clinical trial NCT03959228: Impact of Low Protein Diet Supplemented With Ketoanalogues Supplementation on Uremic Toxins Production
Official title: Impact of Low Protein Diet Supplemented With Ketoanalogues on Uremic Toxins Production and Glucose Metabolism in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Renal Failure
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2019-05-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Indoxyl Sulfate Plasmatic concentration
timeFrame: After 3 months of diet
Secondary outcomes:
measure: TMAO uremic toxin concentraction ( TMAO, PCS) in plasma
timeFrame: After 3 months
measure: TMAO uremic toxin concentraction in urine ( IS, PCS)
timeFrame: After 3 months
measure: Composition of intestinal microbiota
timeFrame: Before three months
measure: Composition of intestinal microbiota
timeFrame: After three months
measure: Insulin sensitivity
timeFrame: After 3 months
measure: Insulin secretion
timeFrame: After 3 months
measure: Secretion of gut hormone like GLP-1 and FGF19
timeFrame: After 3 months
measure: Composition of bile acid
timeFrame: After 3 months
measure: Concentration of bile acid
timeFrame: After 3 months
measure: Concentration of endotoxinemia (LPS)
timeFrame: After 3 months
measure: Nutritional status
timeFrame: After 3 months
measure: Calcemia
timeFrame: After 3 months
measure: Observance of diet
timeFrame: After 3 months
Other outcomes:
Locations:
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon SUD
Study officials:
References: