Bile Acids and Incretins in Pancreas Kidney Transplant Patients

Study Overview
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Brief Summary
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Pancreas Kidney Transplantation (PKT) is the prominent treatment for type 1 diabetic patients with chronic kidney disease and improves patients' outcome. However, in spite of an optimized systemic insulin substitution, altered glucose metabolism and beta cell function are reported in these patients. The mechanisms behind these abnormalities are still unclear. Duodena-pancreatic anastomosis is performed in a heterotopic site (ileum) and thus could change physical and chemical properties of intestinal secretions, gut flora, as well as intestinal permeability. The effect of this procedure on gut derived metabolic factors, the enterohepatic cycle of bile acids, incretin secretion and intestinal flora have never been studied. This pilot prospective, study is aimed to evaluate the modification of bile acids concentrations and composition in PKT subjects, and the impact in glucose and incretin metabolism (measured by oral glucose tolerance test) one year after transplantation. The results will be compared to those of kidney transplant patients and control subjects.

Official Title
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Impact of Duodena-pancreatic Transplantation on Bile Acids and Incretins Metabolism.

Conditions
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Kidney Transplantation, Pancreas-kidney Transplantation

Intervention / Treatment
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* Procedure: pancreas kidney transplantation
* Procedure: kidney transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients : BMI <30 kg/m2 Candidate for a first kidney transplant with a donor without the United Network for Organ Sharing (UNOS) criteria of extended donors and including living donors and pancreas-kidney donors (duodena-pancreas with ileal anastomosis and systemic drainage) Patients with conventional immunosuppression (maintenance with steroids, Tacrolimus and Mycophenolate Mofetil Willing and able to give informed consent Control subjects : Potential living kidney donor Exclusion Criteria: Subjects with a history of colectomy, gut resection or cholecystectomy For women : pregnancy Type 2 diabetes Type 1 diabetes

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pancreas kidney transplant<br>Patients with pancreas kidney transplantation | Procedure: pancreas kidney transplantation<br> <br> |
| Experimental: kidney transplant subjects<br>Patients with kidney transplantation | Procedure: kidney transplantation<br> <br> |
| No Intervention: Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bile acids concentrations | Plasmatic bile acids concentration will be measured in serum by biochemical analysis | One year after transplantation | 
| Bile acids composition | Plasmatic bile acids composition will be assessed in serum by gas chromatography | One year after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between bile acid modifications and Oral Glucose Tolerance test (OGT) measures | OGT will be performed in all subjects. Data on insulin sensitivity and secretion, Glucagon-Like Peptide 1 (GLP-1) and fibroblast growth factor-19 will be collected | One year after transplantation | 
| Impact of Pancreas-Kidney Transplantation (PKT) on LipoPolySaccharides (LPS) | LPS level will be measured before transplantation and one year after transplantation | One year after transplantation | 
| Impact of PKT on intestinal flora | Gut microbiota will be analysed before and after transplantation | One year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bile acids, pancreas kidney transplantation, incretins, intestinal flora