Microbiome and Immunosuppression: The Mission Study

Study Overview
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Brief Summary
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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. We want to study how the microbiome affects how your body process the transplant medication.

Detailed Description
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Immunosuppression drugs, like antibiotics and certain foods, can change the microbiome (the natural micro-organisms inside the body) of the individual taking the drug. We want to study what impact these changes to the microbiome have on the individual. We are specifically interested in how these changes to the microbiome may change the metabolism (breakdown) and action of medications. We already know that individual genetics impact the metabolism, absorption, and toxicities of some medications. We suspect 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, we can more accurately prescribe and dose these medications to better treat and care for our transplant patients and their organs. We expect that you will be in this research study for up to 12 years. There will be periods of time that require your active participation (visits) and periods of time that will be more passive participation (allowing our study staff to follow-up your medical records for outcomes).

Official Title
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Microbiome and Immunosuppression: The Mission Study

Conditions
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Kidney Transplant Rejection, Kidney Transplant

Intervention / Treatment
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* Other: collection of body microbioma


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1) Participants undergoing kidney transplant 2) Male or female at least 18 years of age at time of enrollment 3) Will or have received a living or deceased donor kidney transplant 4) 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). 5) Able and willing to complete study-related procedures and visits 6) Signs written informed consent Exclusion Criteria: 1) Recipient of a previous non-kidney transplant 2) Subject is a multi-organ transplant recipient 3) Presence of active gastroparesis and documented in medical record 4) Liver dysfunction (total bilirubin >2x upper limit of normal) within 2 months of enrollment 5) Patients that take medications that significantly inhibit UGT enzymes. 6) Patients that take medications that significantly inhibit or induce the biliary transporters 7) Patient is known to be HIV positive 8) Pregnant or nursing (lactating) women 9) Non-English speaking 10) Patients who have undergone bariatric surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1 - This is a multicenter microbiome and pharmacokinetic study.<br>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. | Other: collection of body microbioma<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the relationship between transplant graft outcomes and urinary transcriptome. | 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. | 5 years | 
| To assess the relationship between kidney graft outcomes and stool, oral, nasal and urine microbiome diversity. | The gut microbiome has been implicated in the variability in metabolism of drugs with specific microbial species being associated with direct and indirect effects. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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transplant, kidney, Microbiome