- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04360031
The Effects of Microbiota Composition on Immunosuppression Protocols in Transplantation
Investigating the Links Between Microbiota Composition and Variability Observed in the Pharmacological Response to Immunosuppressive Therapies in Kidney Transplant Patients.
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.
Study Overview
Status
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Michel MOURAD, MD
- Phone Number: 003227642213
- Email: michel.mourad@uclouvain.be
Study Contact Backup
- Name: Laure ELENS, PhD
- Phone Number: 003227647227
- Email: laure.elens@uclouvain.be
Study Locations
-
-
-
Bruxelles, Belgium, 1200
- Recruiting
- Cliniques universitaires Saint-Luc
-
Contact:
- Michel MOURAD, MD
- Phone Number: 003227642213
- Email: michel.mourad@uclouvain.be
-
Principal Investigator:
- Laure ELENS, PhD
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Principal Investigator:
- Vincent HAUFROID, MD
-
Sub-Investigator:
- Laure BINDELS, PhD
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Sub-Investigator:
- Serge MOUDIO, MD/PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Tacrolimus / Mycophenolate Mofetil
All patients receive maintenance immunosuppressive treatment of tacrolimus in combination with Mycophenolate Mofetil.
|
Tacrolimus and Mycophenolate Mofetil are given in accordance with patient's current regimen
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Study of the links between immunosuppressive drugs pharmacology and intestinal microbiota composition
Time Frame: 24 months
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Identify links between oral dosage and concentrations found in feces
Time Frame: 18 months
|
Study the concentrations of Tacrolimus and Mycophenolate (MPA) Mofetil in feces and highlight predictors depending on microbiota composition
|
18 months
|
Identify genetic factors underlying the links between microbiota and Tacrolimus/Mycophenolate Mofetil
Time Frame: 18 months
|
Investigate microbial genes responsible for associations between microbiota composition and immuno-suppressant pharmacology
|
18 months
|
Tacrolimus concentrations and microbiota
Time Frame: 18 months
|
Identify links between microbiota composition and Tacrolimus concentrations in blood.
|
18 months
|
Tacrolimus concentrations and genetic polymorphisms
Time Frame: 18 months
|
Identify genetic factors able to influence Tac concentrations in blood.
|
18 months
|
Tacrolimus concentration and demographics
Time Frame: 18 months
|
Investigate the effect of sex and age on Tac concentrations in blood.
|
18 months
|
Mycophenolate Mofetil concentration and microbiota
Time Frame: 18 months
|
Identify links between microbiota composition and MPA Mofetil concentration in blood and urine.
|
18 months
|
Mycophenolate Mofetil concentration and polymorphisms
Time Frame: 18 months
|
Identify genetic factors able to influence MPA Mofetil concentrations in blood and urine.
|
18 months
|
Mycophenolate Mofetil concentration and demographics
Time Frame: 18 months
|
Investigate the effect of sex and age on MPA Mofetil concentrations in blood and urine.
|
18 months
|
Investigate potential markers of kidney function in metabolites
Time Frame: 18 months
|
Study metabolomics in urine from patients to identify specific markers of kidney function
|
18 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Vincent Haufroid, MD, Université Catholique de Louvain
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Tacrolimus
- Mycophenolic Acid
Other Study ID Numbers
- Microbiota/TAC/MPA
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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