The Effects of Microbiota Composition on Immunosuppression Protocols in Transplantation

Immunosuppression Clinical Trial

Official title:

Investigating the Links Between Microbiota Composition and Variability Observed in the Pharmacological Response to Immunosuppressive Therapies in Kidney Transplant Patients.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04360031
• Other study ID #: Microbiota/TAC/MPA
• Status: Recruiting
• Start date: February 10, 2020
• Est. completion date: March 2021

Study information

• Verified date: February 2020
• Source: Université Catholique de Louvain
• Contact: MICHEL MOURAD, MD
• Phone: 003227642213
• Email: michel.mourad[@]uclouvain.be
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Solid organ transplantation is the treatment of choice for patients suffering from end-stage organ disease, including for chronic kidney failure. The implementation of effective immunosuppressive therapies has already significantly improved the prognosis for graft survival. However, these therapies are often associated with considerable inter- and intra-individual variability both in terms of response or in terms of pharmacokinetics. Innovative approaches must be considered, such as studying the involvement of intestinal microbiota in the pharmacology of these drugs.

The general aim of the study is therefore to relate the variabilities observed in the pharmacology (mainly pharmacokinetics) of immunosuppressive drugs used in renal transplantation (tacrolimus and mycophenolate mofetil) and the composition of the intestinal microbiota of renal transplant patients.

Description:

Solid-organ transplantation often requires the implementation of a lifelong immunosuppressive therapy. A combination of tacrolimus (TAC), mycophenolate mofetil (MMF), together with steroids is currently used in over 60% of cases. In some patients however, these therapies are associated with high levels of variability, either in terms of response to treatments or in terms of pharmacokinetics, which remains unexplained. To address the issue, new approaches are being considered, in this study we will investigate the involvement of the intestinal microbiota in the pharmacology of these drugs. This is a particularly promising avenue for drugs with a low therapeutic index and large intra- and inter-individual pharmacokinetic variabilities such as tacrolimus and mycophenolate mofetil. Despite promising preliminary data for tacrolimus, the influence of the gut microbiota in these pharmacokinetic variabilities remains unclear, even less data are available about the involvement of the microbiota in the pharmacokinetics of mycophenolate mofetil.

We expect that this study will produce additional information on the effect of immunosuppression drugs on gut microbiota, and the relationship between microbiota composition and variabilities.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: March 2021
• Est. primary completion date: March 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients within 1 to 8 years post transplantation

• Aged between 18 and 75 years old

• Patients receiving tacrolimus and mycophenolate mofetil as part of their immunosuppressive therapy

• French speaking

• BMI between 18 and 30.

Exclusion Criteria:

• Use of tobacco

• Potential Alcohol problems (less than two positive answers to the CAGE questionnaire)

• Use of antibiotic medication within 3 months of the sample collection

• Use of laxative medication within 2 weeks of the sample collection

• Use of anti-fungal medication within 2 weeks of the sample collection

• Pregnant or lactating patients.

Related Conditions & MeSH terms

• Immunosuppression
• Kidney Transplant; Complications
• Transplant Failure

Intervention

Drug:
• Tacrolimus
Tacrolimus and Mycophenolate Mofetil are given in accordance with patient's current regimen

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Bruxelles

Sponsors (1)

Lead Sponsor	Collaborator
Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Study of the links between immunosuppressive drugs pharmacology and intestinal microbiota composition	The general aim of the study is to relate the variabilities observed in the pharmacology (mainly pharmacokinetics) of immunosuppressive drugs used in kidney transplantation (tacrolimus and mycophenolate mofetil) and the composition of the intestinal microbiota of these patients.	24 months
Secondary	Identify links between oral dosage and concentrations found in feces	Study the concentrations of Tacrolimus and Mycophenolate (MPA) Mofetil in feces and highlight predictors depending on microbiota composition	18 months
Secondary	Identify genetic factors underlying the links between microbiota and Tacrolimus/Mycophenolate Mofetil	Investigate microbial genes responsible for associations between microbiota composition and immuno-suppressant pharmacology	18 months
Secondary	Tacrolimus concentrations and microbiota	Identify links between microbiota composition and Tacrolimus concentrations in blood.	18 months
Secondary	Tacrolimus concentrations and genetic polymorphisms	Identify genetic factors able to influence Tac concentrations in blood.	18 months
Secondary	Tacrolimus concentration and demographics	Investigate the effect of sex and age on Tac concentrations in blood.	18 months
Secondary	Mycophenolate Mofetil concentration and microbiota	Identify links between microbiota composition and MPA Mofetil concentration in blood and urine.	18 months
Secondary	Mycophenolate Mofetil concentration and polymorphisms	Identify genetic factors able to influence MPA Mofetil concentrations in blood and urine.	18 months
Secondary	Mycophenolate Mofetil concentration and demographics	Investigate the effect of sex and age on MPA Mofetil concentrations in blood and urine.	18 months
Secondary	Investigate potential markers of kidney function in metabolites	Study metabolomics in urine from patients to identify specific markers of kidney function	18 months