Kidney Transplant; ComplicationsNCT04360031
The Effects of Microbiota Composition on Immunosuppression Protocols in Transplantation
An observational study of Kidney Transplant; Complications and Immunosuppression, run by Université Catholique de Louvain at 1 site in Belgium.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Kidney Transplant; Complications, Immunosuppression, Transplant Failure
- What is being tested?
- Tacrolimus
- How many people
- 100 participants
- Where
- 1 siteBelgium
- Study dates
- 10 Feb 2020to Mar 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
Cliniques universitaires Saint-Luc
Brussels, 1200
Michel MOURAD, MD, 003227642213, michel.mourad@uclouvain.be
Laure ELENS, PhD
About this study
Official title: 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.
Read the 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.
- Being tested
- Tacrolimus
- Keywords
- Tacrolimus, Mycophenolate Mofetil, Transplantation, Kidney transplant, Calcineurin inhibitors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Mycophenolate Mofetil
Tacrolimus and Mycophenolate Mofetil are given in accordance with patient's current regimen
| Study group | Role | What they receive |
|---|---|---|
| Tacrolimus / Mycophenolate Mofetil | All patients receive maintenance immunosuppressive treatment of tacrolimus in combination with Mycophenolate Mofetil. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (9)
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
Measured: 18 months
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
Measured: 18 months
Tacrolimus concentrations and microbiota
Identify links between microbiota composition and Tacrolimus concentrations in blood.
Measured: 18 months
Tacrolimus concentrations and genetic polymorphisms
Identify genetic factors able to influence Tac concentrations in blood.
Measured: 18 months
Tacrolimus concentration and demographics
Investigate the effect of sex and age on Tac concentrations in blood.
Measured: 18 months
Mycophenolate Mofetil concentration and microbiota
Identify links between microbiota composition and MPA Mofetil concentration in blood and urine.
Measured: 18 months
Mycophenolate Mofetil concentration and polymorphisms
Identify genetic factors able to influence MPA Mofetil concentrations in blood and urine.
Measured: 18 months
Mycophenolate Mofetil concentration and demographics
Investigate the effect of sex and age on MPA Mofetil concentrations in blood and urine.
Measured: 18 months
Investigate potential markers of kidney function in metabolites
Study metabolomics in urine from patients to identify specific markers of kidney function
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2020
- Study start10 Feb 2020
- Primary completionMar 2021 (estimated)
- Study completionMar 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney Transplant; ComplicationsStudies of the same condition, open and under way.
- More trials run by Université Catholique de LouvainThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Université Catholique de Louvain
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent Haufroid, MD, Principal investigator, Université Catholique de Louvain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04360031
- Sponsor's protocol ID
- Microbiota/TAC/MPA
- Status last verified
- Feb 2020
- First submitted
- 21 Apr 2020
- Last updated
- 24 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Publications
Degraeve AL, Bindels LB, Haufroid V, Moudio S, Boland L, Delongie KA, Dewulf JP, Eddour DC, Mourad M, Elens L. Tacrolimus Pharmacokinetics is Associated with Gut Microbiota Diversity in Kidney Transplant Patients: Results from a Pilot Cross-Sectional Study. Clin Pharmacol Ther. 2024 Jan;115(1):104-115. doi: 10.1002/cpt.3077. Epub 2023 Oct 30.
PubMed 37846607
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Links Between Microbiota Composition and Variability Observed in the Pharmacological Response to Immunosuppressive Therapies in Kidney Transplant Patients.
- ClinicalTrials.gov ID
- NCT04360031
- Acronym / sponsor ID
- Microbiota/TAC/MPA
- Keywords
- Tacrolimus, Mycophenolate Mofetil, Transplantation, Kidney transplant, Calcineurin inhibitors
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Université Catholique de LouvainUniversity, hospital or other
- Study start
- 10 Feb 2020 (actual)
- Primary completion
- Mar 2021 (estimated)
- Study completion
- Mar 2021 (estimated)
- First posted
- 24 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tacrolimus / Mycophenolate Mofetil | – | Drug: TacrolimusAll patients receive maintenance immunosuppressive treatment of tacrolimus in combination with Mycophenolate Mofetil. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: Mycophenolate MofetilTacrolimus and Mycophenolate Mofetil are given in accordance with patient's current regimen | Drug | Tacrolimus / Mycophenolate Mofetil |
Primary outcome
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.
9 secondary outcomes
Identify links between oral dosage and concentrations found in feces
Time frame: 18 months
Identify genetic factors underlying the links between microbiota and Tacrolimus/Mycophenolate Mofetil
Time frame: 18 months
Tacrolimus concentrations and microbiota
Time frame: 18 months
Tacrolimus concentrations and genetic polymorphisms
Time frame: 18 months
Tacrolimus concentration and demographics
Time frame: 18 months
Mycophenolate Mofetil concentration and microbiota
Time frame: 18 months
Mycophenolate Mofetil concentration and polymorphisms
Time frame: 18 months
Mycophenolate Mofetil concentration and demographics
Time frame: 18 months
Investigate potential markers of kidney function in metabolites
Time frame: 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2020.
- Derived from this study: PubMed 37846607Degraeve AL, Bindels LB, Haufroid V, Moudio S, Boland L, Delongie KA, Dewulf JP, Eddour DC, Mourad M, Elens L. Tacrolimus Pharmacokinetics is Associated with Gut Microbiota Diversity in Kidney Transplant Patients: Results from a Pilot Cross-Sectional Study. Clin Pharmacol Ther. 2024 Jan;115(1):104-115. doi: 10.1002/cpt.3077. Epub 2023 Oct 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vincent Haufroid, MD principal investigator
Université Catholique de Louvain
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplant; Complications and Immunosuppression, run by Université Catholique de Louvain at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MICHEL MOURAD, MD (003227642213, michel.mourad@uclouvain.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study of the links between immunosuppressive drugs pharmacology and intestinal microbiota composition (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04360031, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2020.