Microbiome and Immunosuppression: The Mission Study

Active, not recruiting

• Conditions: Kidney Transplant Rejection; Kidney Transplant
• Interventions: Other: collection of body microbioma

• Registration Number: NCT04953715
• Lead Sponsor: Ajay Israni

Brief Summary

The purpose of this research is to study immunosuppression drugs, certain foods, and how they can change the microbiome (the natural microorganisms inside the body) of the individual taking the immunosuppressive medications. The study team wants to study how the microbiome affects how the body processes the transplant medication.

Detailed Description

Immunosuppression drugs, like antibiotics and certain foods, can change the microbiome (the natural micro-organisms inside the body) of the individual taking the drug. The study team wants to study what impact these changes to the microbiome have on the individual. The study team is specifically interested in how these changes to the microbiome may change the metabolism (breakdown) and action of medications. It is already known that individual genetics impact the metabolism, absorption, and toxicities of some medications. It is suspected that the microbiome will have similar impacts on medications. With a better understanding of how individual microbiome impacts immunosuppressant medications used to help transplant recipients from rejecting their new organs, providers can more accurately prescribe and dose these medications to better treat and care for transplant patients and their organs.

It is expected that participants will be in this research study for up to 12 years. There will be periods of time that requires active participation (visits) and periods of time that will be more passive participation (allowing study staff to follow-up with medical records for outcomes).

Study Timeline

• Study Start: 2020-02-12
• Study First Submitted: 2021-06-28
• Study First Submitted QC: 2021-07-02
• Study First Posted: 2021-07-08
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-29
• Primary Completion: 2032-01-01
• Study Completion: 2033-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 146

Inclusion Criteria

• Participants undergoing kidney transplant
• Male or female at least 18 years of age at time of enrollment
• Will or have received a living or deceased donor kidney transplant
• Planned post-transplant immunosuppression regimen of mycophenolate mofetil dosed every 12 hours (Cellcept or generic) and immediate release tacrolimus dosed twice daily with trough concentration monitoring (generic or brand formulation).
• Able and willing to complete study-related procedures and visits
• Signs written informed consent

Exclusion Criteria

• Recipient of a previous non-kidney transplant
• Subject is a multi-organ transplant recipient
• Presence of active gastroparesis and documented in medical record
• Liver dysfunction (total bilirubin >2x upper limit of normal) within 2 months of enrollment
• Patients that take medications that significantly inhibit UGT enzymes.
• Patients that take medications that significantly inhibit or induce the biliary transporters
• Patient is known to be HIV positive
• Pregnant or nursing (lactating) women
• Non-English speaking
• Patients who have undergone bariatric surgery

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1 - This is a multicenter microbiome and pharmacokinetic study.	collection of body microbioma	A prospective, observational microbiome study of adult kidney transplant recipients receiving mycophenolate mofetil and tacrolimus maintenance immunosuppression. Participants will be studied post-transplant for mycophenolate pharmacokinetics and microbiome samples collected. Clinically measured tacrolimus trough concentrations will also be evaluated. Associations among mycophenolic acid enterohepatic recycling and metabolite formation, tacrolimus troughs, immunosuppression adverse effects, diarrhea and microbiome will be studied. To assess the relationship between kidney graft outcomes and stool, oral, nasal and urine microbiome diversity. To assess the relationship between transplant graft outcomes and urinary transcriptome.

Primary Outcome Measures

Name	Time	Method
To assess the relationship between kidney graft outcomes and stool, oral, nasal and urine microbiome diversity.	5 years	The gut microbiome has been implicated in the variability in metabolism of drugs with specific microbial species being associated with direct and indirect effects.
To assess the relationship between transplant graft outcomes and urinary transcriptome.	5 years	The gut microbiome has been implicated in the Stool from tx recipients with diarrhea is often sent for testing of potential pathogenic organisms. PCR based approaches to identify etiology of posttx diarrhea only tests for a limited number of organisms.

Trial Locations

Locations (2)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

HCMC; 🇺🇸 Minneapolis, Minnesota, United States