Kidney Transplant; ComplicationsPhase 4MicrobioTacNCT04207177
Immunosuppressive Drugs and Gut Microbiome: Pharmacokinetic- and Microbiome Diversity Effects
A Phase 4 study testing Mycophenolate Mofetil 500 mg Tab and Tacrolimus capsule in people with Kidney Transplant; Complications and Immune Suppression, run by Oslo University Hospital at 1 site in Norway.
Trial summary
Kidney transplant recipients of living- and deceased donor grafts and treated with both mycophenolate mofetil (MMF) and tacrolimus (Tac) will be included. A 12-hour pharmacokinetic (PK) investigation of both mycophenolate (MPA) and Tac will be performed in pharmacokinetic steady state conditions between 3 to 8 weeks… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Transplant; Complications, Immune Suppression
- What is being tested?
- Mycophenolate Mofetil 500 mg Tab and Tacrolimus capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteNorway
- Study dates
- 30 Oct 2019to 31 Dec 2025
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- De novo standard risk kidney transplant recipients.
- Patients scheduled to receive tacrolimus and mycophenolate mofetil as part of their immunosuppressive therapy following transplantation (clinical decision not influenced by this study).
- First kidney transplant only.
- Adult patients.
Who cannot join
- Pregnant or lactating female patients.
Trial locations and contacts
1 site in 1 country.
About this study
Kidney transplant recipients of living- and deceased donor grafts and treated with both mycophenolate mofetil (MMF) and tacrolimus (Tac) will be included. A 12-hour pharmacokinetic (PK) investigation of both mycophenolate (MPA) and Tac will be performed in pharmacokinetic steady state conditions between 3 to 8 weeks and one year after transplantation. Feces samples will be collected before (if possible), 1 week after transplantation and at the day of the 12-hour PK investigations. Data on dietary intake and physical activity will be obtained in association with the feces sampling in all patients. Patients will be invited to a follow-up visit one year after transplantation where the 12-hour PK investigation, feces sampling, dietary and activity data collection is repeated. Standard follow-up data after renal transplantations, such as acute rejection episodes, infections, renal function, post transplant diabetes mellitus (PTDM), protocol biopsies, adherence to immunosuppressive drugs, graft loss and death will be collected for all patients up to 5 years after transplantation according to standard schedule at the transplant center.
A subgroup of kidney transplant recipients scheduled for living donor transplantation will be included before transplantation for pre-transplant investigations in addition to the investigations after transplantation. These patients will be randomized to either receive one week of treatment with MMF or Tac before transplantation. Feces samples and a 12-hour PK investigation will be performed after one week of treatment (before transplantation).
Read the detailed description
The analyses of feces samples will be performed by utilizing shotgun, next generation sequencing in order to determine the bacterial, fungal sand viral microbiome. Drug concentrations will be analyzed with high performance Liquid chromatography With double mass spectrometry detector (HPLC-MS/MS) technology and both free and total plasma MPA concentrations, total mycophenolate glucoronide (MPAG) concentrations and total whole blood Tac and methylated Tac-metabolite concentrations will be determined.
- Being tested
- Mycophenolate Mofetil 500 mg Tab, Tacrolimus capsule
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mycophenolate Mofetil 500 mg TabDrug
Also called MMF-arm
Twice daily dosing of MMF only for a week before transplantation in this subgroup. All patients will get maintenance treatment With MMF in combination With tacrolimus and steroids after transplantation.
Tacrolimus capsuleDrug
Also called Tac-arm
Twice daily dosing of tacrolimus only for a week before transplantation in this subgroup. All patients will get maintenance treatment With tacrolimus in combination With MMF and steroids after transplantation.
| Study group | Role | What they receive |
|---|---|---|
| Mycophenolate mofetil | Active comparator | In the subgroup of living donor recipients included before transplantation this group will be treated with mycophenolate mofetil (750 mg BID) for one week Receives: Drug: Mycophenolate Mofetil 500 mg Tab |
| Tacrolimus | Active comparator | In the subgroup of living donor recipients included before transplantation this group will be treated with tacrolimus (BID, dose by weight) for one week Receives: Drug: Tacrolimus capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
investigate the association between microbiome diversity and 12-hour mycophenolate area under the curve (AUC)
Association between microbiome diversity measures and AUC of mycophenolate for a dose interval (AUC0-tau)
Measured: 1 year
investigate the association between microbiome diversity and 12-hour mycophenolate Maximum concentration (Cmax)
Association between microbiome diversity measures and Cmax of mycophenolate
Measured: 1 year
Secondary outcomes (14)
association between microbiome diversity and 12-hour tacrolimus AUC
Association between microbiome diversity measures and AUC0-tau of tacrolimus
Measured: 1 year
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate AUC changes
Changes in microbiome diversity measures and mycophenolate AUC0-tau, with one week of mycophenolate mofetil treatment.
Measured: 1 week
investigate the effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus AUC changes
Changes in microbiome diversity measures and tacrolimus AUC0-tau with one week of tacrolimus treatment
Measured: 1 week
investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient
Associations between TTV viral load (DNAemia) and acute rejection episodes (biopsy proven)
Measured: 1 year
Association between microbiome diversity measures and Cmax of tacrolimus
Association between microbiome diversity measures and Cmax of tacrolimus
Measured: 1 year
Association between microbiome diversity measures and absolute bioavailability (F) of tacrolimus
Association between microbiome diversity measures and F of tacrolimus
Measured: 1 year
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate Cmax changes
Changes in microbiome diversity measures and mycophenolate Cmax with one week of mycophenolate mofetil treatment.
Measured: 1week
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate time to Cmax (Tmax) changes
Changes in microbiome diversity measures and mycophenolate Tmax with one week of mycophenolate mofetil treatment.
Measured: 1week
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate time to terminal phase elimination rate constant (kel)changes
Changes in microbiome diversity measures and mycophenolate kel with one week of mycophenolate mofetil treatment.
Measured: 1 week
effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus time to Cmax (Tmax) changes
Changes in microbiome diversity measures and tacrolimus Cmax with one week of tacrolimus treatment.
Measured: 1 week
effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus time to Cmax (Tmax) changes
Changes in microbiome diversity measures and tacrolimus Tmax with one week of tacrolimus treatment.
Measured: 1 week
effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus time to terminal phase elimination rate constant (kel) changes
Changes in microbiome diversity measures and tacrolimus kel with one week of tacrolimus treatment.
Measured: 1 week
investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient
Associations between TTV viral load (DNAemia) and opportunistic vial infections in need of drug treatment
Measured: 1 year
investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient
Associations between TTV viral load (DNAemia) and opportunistic bacterial infections requiring hospitalization
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start30 Oct 2019
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Kidney Transplant; ComplicationsStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- The main study is based on treatment allocation outside of thsi protocol but a subgroup of living donor recipients will be randomized to wither one week tacrolimus or mycophenolate mofetil treatment before transplantation.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anders Åsberg, Oslo University Hospital
- Investigators
- Karsten Midtvedt, MD, PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04207177
- Sponsor's protocol ID
- MicrobioTac-MPA
- Acronym
- MicrobioTac
- Status last verified
- Apr 2024
- First submitted
- 17 Dec 2019
- Last updated
- 4 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Not allowed by Norwegian Law to share data without specific contract. Upon contact With the responsible investigator it is however possible to share data under a specified contract
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immunosuppressive Drugs and Gut Microbiome: Pharmacokinetic- and Microbiome Diversity Effects
- ClinicalTrials.gov ID
- NCT04207177
- Acronym / sponsor ID
- MicrobioTac / MicrobioTac-MPA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 30 Oct 2019 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 20 Dec 2019 (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.
Kidney transplant recipients of living- and deceased donor grafts and treated with both mycophenolate mofetil (MMF) and tacrolimus (Tac) will be included. A 12-hour pharmacokinetic (PK) investigation of both mycophenolate (MPA) and Tac will be performed in pharmacokinetic steady state conditions between 3 to 8 weeks and one year after transplantation. Feces samples will be collected before (if possible), 1 week after transplantation and at the day of the 12-hour PK investigations. Data on dietary intake and physical activity will be obtained in association with the feces sampling in all patients. Patients will be invited to a follow-up visit one year after transplantation where the 12-hour PK investigation, feces sampling, dietary and activity data collection is repeated. Standard follow-up data after renal transplantations, such as acute rejection episodes, infections, renal function, post transplant diabetes mellitus (PTDM), protocol biopsies, adherence to immunosuppressive drugs, graft loss and death will be collected for all patients up to 5 years after transplantation according to standard schedule at the transplant center.
A subgroup of kidney transplant recipients scheduled for living donor transplantation will be included before transplantation for pre-transplant investigations in addition to the investigations after transplantation. These patients will be randomized to either receive one week of treatment with MMF or Tac before transplantation. Feces samples and a 12-hour PK investigation will be performed after one week of treatment (before transplantation).
Detailed description
The analyses of feces samples will be performed by utilizing shotgun, next generation sequencing in order to determine the bacterial, fungal sand viral microbiome. Drug concentrations will be analyzed with high performance Liquid chromatography With double mass spectrometry detector (HPLC-MS/MS) technology and both free and total plasma MPA concentrations, total mycophenolate glucoronide (MPAG) concentrations and total whole blood Tac and methylated Tac-metabolite concentrations will be determined.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The main study is based on treatment allocation outside of thsi protocol but a subgroup of living donor recipients will be randomized to wither one week tacrolimus or mycophenolate mofetil treatment before transplantation.
| Arm | Type | Receives |
|---|---|---|
| Mycophenolate mofetil | Active comparator | Drug: Mycophenolate Mofetil 500 mg TabIn the subgroup of living donor recipients included before transplantation this group will be treated with mycophenolate mofetil (750 mg BID) for one week |
| Tacrolimus | Active comparator | Drug: Tacrolimus capsuleIn the subgroup of living donor recipients included before transplantation this group will be treated with tacrolimus (BID, dose by weight) for one week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- De novo standard risk kidney transplant recipients.
- Patients scheduled to receive tacrolimus and mycophenolate mofetil as part of their immunosuppressive therapy following transplantation (clinical decision not influenced by this study).
- First kidney transplant only.
- Adult patients.
Key exclusion criteria (1 listed)
- Pregnant or lactating female patients.
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 |
|---|---|---|
| Mycophenolate Mofetil 500 mg TabAlso: MMF-armTwice daily dosing of MMF only for a week before transplantation in this subgroup. All patients will get maintenance treatment With MMF in combination With tacrolimus and steroids after transplantation. | Drug | Mycophenolate mofetil |
| Tacrolimus capsuleAlso: Tac-armTwice daily dosing of tacrolimus only for a week before transplantation in this subgroup. All patients will get maintenance treatment With tacrolimus in combination With MMF and steroids after transplantation. | Drug | Tacrolimus |
Primary outcome
investigate the association between microbiome diversity and 12-hour mycophenolate area under the curve (AUC)
Time frame: 1 year
Association between microbiome diversity measures and AUC of mycophenolate for a dose interval (AUC0-tau)
investigate the association between microbiome diversity and 12-hour mycophenolate Maximum concentration (Cmax)
Time frame: 1 year
Association between microbiome diversity measures and Cmax of mycophenolate
14 secondary outcomes
association between microbiome diversity and 12-hour tacrolimus AUC
Time frame: 1 year
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate AUC changes
Time frame: 1 week
investigate the effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus AUC changes
Time frame: 1 week
investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient
Time frame: 1 year
Association between microbiome diversity measures and Cmax of tacrolimus
Time frame: 1 year
Association between microbiome diversity measures and absolute bioavailability (F) of tacrolimus
Time frame: 1 year
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate Cmax changes
Time frame: 1week
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate time to Cmax (Tmax) changes
Time frame: 1week
effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate time to terminal phase elimination rate constant (kel)changes
Time frame: 1 week
effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus time to Cmax (Tmax) changes
Time frame: 1 week
effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus time to Cmax (Tmax) changes
Time frame: 1 week
effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus time to terminal phase elimination rate constant (kel) changes
Time frame: 1 week
investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient
Time frame: 1 year
investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2024.
- Individual participant dataSharing planned: No. Not allowed by Norwegian Law to share data without specific contract. Upon contact With the responsible investigator it is however possible to share data under a specified contract
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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.
Karsten Midtvedt, MD, PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mycophenolate Mofetil 500 mg Tab and Tacrolimus capsule in people with Kidney Transplant; Complications and Immune Suppression, run by Oslo University Hospital at 1 site in Norway.
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 4 inclusion and 1 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 4 Apr 2024. 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 Norway. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
investigate the association between microbiome diversity and 12-hour mycophenolate area under the curve (AUC) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Apr 2024.