Clinical trial NCT04360031: The Effects of Microbiota Composition on Immunosuppression Protocols in Transplantation
Official title: Investigating the Links Between Microbiota Composition and Variability Observed in the Pharmacological Response to Immunosuppressive Therapies in Kidney Transplant Patients.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Kidney Transplant; Complications
Immunosuppression
Transplant Failure
Keywords: Tacrolimus
Mycophenolate Mofetil
Transplantation
Kidney transplant
Calcineurin inhibitors
Lead sponsor: Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2020-04-24
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Kidney transplant patients followed at the Saint-Luc University Clinics and having been transplanted in the abdominal transplant service of the clinics will be recruited for the study.

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Study of the links between immunosuppressive drugs pharmacology and intestinal microbiota composition
timeFrame: 24 months
Secondary outcomes:
measure: Identify links between oral dosage and concentrations found in feces
timeFrame: 18 months
measure: Identify genetic factors underlying the links between microbiota and Tacrolimus/Mycophenolate Mofetil
timeFrame: 18 months
measure: Tacrolimus concentrations and microbiota
timeFrame: 18 months
measure: Tacrolimus concentrations and genetic polymorphisms
timeFrame: 18 months
measure: Tacrolimus concentration and demographics
timeFrame: 18 months
measure: Mycophenolate Mofetil concentration and microbiota
timeFrame: 18 months
measure: Mycophenolate Mofetil concentration and polymorphisms
timeFrame: 18 months
measure: Mycophenolate Mofetil concentration and demographics
timeFrame: 18 months
measure: Investigate potential markers of kidney function in metabolites
timeFrame: 18 months
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
Study officials:
affiliation: Université Catholique de Louvain
name: Vincent Haufroid, MD
role: PRINCIPAL_INVESTIGATOR
References: