Influence of the Intestinal Microbiota on the Clinical Course of Renal Transplantation

ACKGROUND: The development of new molecular techniques, in recent years, has increasing the knowledge of the composition and functionality of the intestinal microbiota. In the area of kidney transplantation, observational studies have described a change in the intestinal microbiota during the immediate post-transplantation period that seems to be related to the appearance of clinical outcomes such as diarrhea, repeated urinary tract infections, the need for adjustment of immunosuppressive treatment or acute rejection. However, intervention studies on this subject are necessary to determine how far the microbiota can influence in the development of these events.

OBJECTIVE: To clarify the influence of maintaining the composition and functionality of the intestinal microbiota on post-transplant clinical outcomes such as diarrhea, urinary tract infections, kidney graft rejection and the need for dose adjustment of immunosuppressive therapy.

MATERIALS AND METHODS: single-center, randomized, interventional pilot study with 50 deceased kidney donor transplant patients at low immunological risk. Each patient will be randomized at the time of inclusion in the study to one of the 2 branches of the study: 1) Intervention group: 25 patients who will receive a autologous fecal matter transfer during the first 6 months post-transplantation, 2) Control group: 25 renal transplant patients with the same characteristics who will not receive any type of intervention in addition to the immunosuppressive treatment indicated according to hospital protocol.

Study Overview

• Status: Recruiting
• Conditions: Renal Transplant
• Intervention / Treatment: Dietary supplement: Control; Dietary supplement: Microbiota autotransplantation

Detailed Description

ACKGROUND: The development of new molecular techniques, in recent years, has increasing the knowledge of the composition and functionality of the intestinal microbiota. In the area of kidney transplantation, observational studies have described a change in the intestinal microbiota during the immediate post-transplantation period that seems to be related to the appearance of clinical outcomes such as diarrhea, repeated urinary tract infections, the need for adjustment of immunosuppressive treatment or acute rejection. However, intervention studies on this subject are necessary to determine how far the microbiota can influence in the development of these events.

OBJECTIVE: To clarify the influence of maintaining the composition and functionality of the intestinal microbiota on post-transplant clinical outcomes such as diarrhea, urinary tract infections, kidney graft rejection and the need for dose adjustment of immunosuppressive therapy.

MATERIALS AND METHODS: single-center, randomized, interventional pilot study with 50 deceased kidney donor transplant patients at low immunological risk. Each patient will be randomized at the time of inclusion in the study to one of the 2 branches of the study: 1) Intervention group: 25 patients who will receive a autologous fecal matter transfer during the first 6 months post-transplantation, 2) Control group: 25 renal transplant patients with the same characteristics who will not receive any type of intervention in addition to the immunosuppressive treatment indicated according to hospital protocol.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esmeralda Castillo Rodríguez, MD; Phone Number: 913368018; Email: esmeralda.castle@gmail.com
• Study Contact Backup: Name: Andrea Collado Alsina, PhD; Phone Number: 913368018; Email: macolladoalsina@gmail.com

Study Locations

• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal
    • Contact: Esmeralda Castillo Rodríguez, MD; Phone Number: 913368018; Email: esmeralda.castle@gmail.com
    • Contact: Andrea Collado Alsina, PhD; Phone Number: 913368018; Email: macolladoalsina@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Recipients of deceased donor kidney transplantation over 18 years of age, able to understand the informed consent form and who have agreed to participate in the study. Only patients with low immunological risk, whose induction for kidney transplantation was performed with basiliximab will be included, regardless of the maintenance immunosuppression combination

Exclusion Criteria:

• Recipients of deceased donor kidney transplant with high immunological risk (within the PATHI kidney transplant program).
• Kidney transplant recipients receiving pretransplant induction with thymoglobulin or polyclonal lymphocyte antiglobulin agents.
• Living donor kidney transplant recipients.
• Patients with a history of intestinal pathology such as: ulcerative colitis, Crohn's disease or malabsorptive syndrome or irritable colon prior to their inclusion in the kidney transplant waiting list.
• Patients with dysphagia, history of aspiration pneumonia or neutropenia prior to transplantation.
• Patients who, even if they meet the inclusion criteria, upon analysis of pretransplant stool, are found to be carriers of enterotoxigenic or potentially pathogenic strains such as Clostridioides difficile, or multiresistant bacteria (BLEE and/or carbapenemase-producing).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Patients of this branch will not have autotransplantation of gut microbiota in capsules and will follow their usual post-transplant treatment	Dietary supplement: Control; Patients will not received microbiota autotransplantation in capsules and will received usual medical care
Active Comparator: Microbiota autotransplantation; Patients in this branch will receive autotransplantation of intestinal microbiota in capsules for 6 months post-transplantation	Dietary supplement: Microbiota autotransplantation; Patients received microbiota autotransplantation in capsules (1g per day) for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the occurrence of diarrhea	Evaluate the occurrence of diarrhea regardless of its cause, between the intervention and control groups. Diarrhea will be defined as three or more bowel movements per day (or more frequently than normal for the individual), and presence of loose or liquid stools, following WHO definition	6 months after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of post-transplant urinary tract infections	Evaluate the occurrence of post-transplant urinary tract infections (UTI), defined as positive urine culture with associated voiding symptoms or fever, as well as positive urine cultures until removal of the double J catheter, given that they will receive antibiotic treatment as if it were a UTI. Positive urine cultures or asymptomatic bacteriuria after removal of the double J catheter (usually at one-month post-transplantation) will not be included in the definition.	6 months after transplantation
Evaluate the dose/level ratio of immunosuppressive drugs	Evaluate the dose/level ratio of immunosuppressive drugs (tacrolimus or everolimus) administered in the intervention groups with respect to the control group	6 months after transplantation
Evaluate the proportion of acute rejection episodes	Evaluate the proportion of acute rejection episodes between the two groups in the follow-up period	6 months after transplantation
Determined Treg lymphocyte populations	Evaluate whether there are differences between the Treg lymphocyte populations in peripheral blood by flow cytometry between the two groups	6 months after transplantation compared to pre transplant situation
Systemic inflammation	Measurement of inflammatory markers in serum by automated systems, such as C-reactive protein	6 months after transplantation
Production of bacterial metabolites	Determination of the short-chain fatty acids (SCFA) concentration as bacterial metabolites in feces and urine by LC-MS/MS as indicators of the functionality of the microbiota	6 months after transplantation compared to pre transplant situation
Analysis of the bacteria composing the microbiota	Analysis of the bacteria composing the microbiota by massive sequencing of the 16S rDNA gene	6 months after transplantation compared to pre transplant situation

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Progression
• Other Study ID Numbers: Microbiota TX (010-20)

Drug and device information, study documents

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