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

Renal Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04874896
• Other study ID #: Microbiota TX (010-20)
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2020
• Est. completion date: September 2025

Study information

• Verified date: May 2023
• Source: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Contact: Esmeralda Castillo Rodríguez, MD
• Phone: 913368018
• Email: esmeralda.castle[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Disease Progression
• Renal Transplant

Intervention

Dietary Supplement:
• Microbiota autotransplantation
Patients received microbiota autotransplantation in capsules (1g per day) for 6 months
• Control
Patients will not received microbiota autotransplantation in capsules and will received usual medical care

Locations

Country	Name	City	State
Spain	Hospital Ramón y Cajal	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Systemic inflammation	Measurement of inflammatory markers in serum by automated systems, such as C-reactive protein	6 months after transplantation
Secondary	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
Secondary	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