NCT04207177

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

• Status: Active Not Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Oslo University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

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.

Conditions

• Kidney Transplant; Complications
• Immune Suppression

Interventions

Type	Name	Description
DRUG	Mycophenolate Mofetil 500 mg Tab	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.
DRUG	Tacrolimus capsule	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.

Timeline

• Start date: 2019-10-30
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2019-12-20
• Last updated: 2024-04-04

Locations

1 site across 1 country: Norway