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

Not Applicable
Recruiting
Conditions
Renal Transplant
Interventions
Dietary Supplement: Microbiota autotransplantation
Dietary Supplement: Control
Registration Number
NCT04874896
Lead Sponsor
Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Brief 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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
50
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Microbiota autotransplantationMicrobiota autotransplantationPatients in this branch will receive autotransplantation of intestinal microbiota in capsules for 6 months post-transplantation
ControlControlPatients of this branch will not have autotransplantation of gut microbiota in capsules and will follow their usual post-transplant treatment
Primary Outcome Measures
NameTimeMethod
Evaluate the occurrence of diarrhea6 months after transplantation

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

Secondary Outcome Measures
NameTimeMethod
Evaluate the dose/level ratio of immunosuppressive drugs6 months after transplantation

Evaluate the dose/level ratio of immunosuppressive drugs (tacrolimus or everolimus) administered in the intervention groups with respect to the control group

Evaluate the proportion of acute rejection episodes6 months after transplantation

Evaluate the proportion of acute rejection episodes between the two groups in the follow-up period

Determined Treg lymphocyte populations6 months after transplantation compared to pre transplant situation

Evaluate whether there are differences between the Treg lymphocyte populations in peripheral blood by flow cytometry between the two groups

Systemic inflammation6 months after transplantation

Measurement of inflammatory markers in serum by automated systems, such as C-reactive protein

Analysis of the bacteria composing the microbiota6 months after transplantation compared to pre transplant situation

Analysis of the bacteria composing the microbiota by massive sequencing of the 16S rDNA gene

Occurrence of post-transplant urinary tract infections6 months after transplantation

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.

Production of bacterial metabolites6 months after transplantation compared to pre transplant situation

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

Trial Locations

Locations (1)

Hospital Ramón y Cajal

🇪🇸

Madrid, Spain

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