Immunosuppressive Drugs and Gut Microbiome: Pharmacokinetic- and Microbiome Diversity Effects

NCT04207177 | Active Not Recruiting Phase 4

• 1 other identifier: MicrobioTac-MPA
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

Kidney Transplant; Complications; Immune Suppression

Outcome Measures

Primary Outcomes (2)

• 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)

  1 year

• investigate the association between microbiome diversity and 12-hour mycophenolate Maximum concentration (Cmax)

  Association between microbiome diversity measures and Cmax of mycophenolate

  1 year

Secondary Outcomes (14)

• association between microbiome diversity and 12-hour tacrolimus AUC

  1 year

• effects of mycophenolate mofetil treatment on gut microbiome changes in treatment naïve patients and associated mycophenolate AUC changes

  1 week

• investigate the effects of tacrolimus treatment on gut microbiome changes in treatment naïve patients and associated tacrolimus AUC changes

  1 week

• investigate if Torque Teno Virus (TTV) is a clinical useful "immunometer", i.e. reflect overall immunosuppression of the recipient

  1 year

• Association between microbiome diversity measures and Cmax of tacrolimus

  1 year

Other Outcomes (2)

• integrate the updated knowledge on mycophenolate and tacrolimus pharmacokinetics following renal transplantation in a combined population pharmacokinetic model for individualized dosing

  1 year

• integrate the updated knowledge on mycophenolate and tacrolimus pharmacokinetics following renal transplantation in a combined population pharmacokinetic model for individualized dosing

  1 year

Study Arms (2)

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

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

Drug: Tacrolimus capsule

Interventions

Mycophenolate Mofetil 500 mg Tab DRUG

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.

Also known as: MMF-arm

Mycophenolate mofetil

Tacrolimus capsule DRUG

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.

Also known as: Tac-arm

Tacrolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \- Pregnant or lactating female patients.

Sponsors & Collaborators

• Oslo University Hospital: lead

Study Sites (1)

Oslo University Hospital

Oslo, 0424, Norway

Location

MeSH Terms

Interventions

Mycophenolic Acid; Tacrolimus

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones

Study Officials

• Karsten Midtvedt, MD, PhD

  Oslo University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Laboratory

Model Details: 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.

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 20, 2019
• Study Start: October 30, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 4, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)