Microbiome and Immunosuppression: The Mission Study

NCT04953715 | Active Not Recruiting

• 4 other identifiers: 24-0273R01AI140303"MISSION" studyK01AI199717-01
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 2

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.

Conditions

Kidney Transplant Rejection; Kidney Transplant

Keywords

transplant; kidney; Microbiome

Outcome Measures

Primary Outcomes (2)

• 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. polymerase chain reaction (PCR)- based approaches to identify etiology of post-tx 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

Study Arms (1)

1 - This is a multicenter microbiome and pharmacokinetic study.

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 microbiome

Interventions

collection of body microbiome OTHER

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.

1 - This is a multicenter microbiome and pharmacokinetic study.

Eligibility Criteria

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

Study Population

Adults kidney transplant recipients with a planned immunosuppression regimen of mycophenolate mofetil dosed every 12 hours and immediate release tacrolimus dosed twice daily.

You may qualify if:

• 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

You may not qualify if:

• Recipient of a previous non-kidney transplant
• Subject is a multi-organ transplant recipient
• Presence of active gastroparesis, and documented in the medical record
• Liver dysfunction (total bilirubin \>2x upper limit of normal) within 2 months of enrollment
• Patients who take medications that significantly inhibit uridine 5'-diphosphate glucuronosyltransferase (UGT) enzymes.
• Patients who 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

Sponsors & Collaborators

• The University of Texas Medical Branch, Galveston: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

University of Minnesota

Minneapolis, Minnesota, 55414, United States

Location

HCMC

Minneapolis, Minnesota, 55415, United States

Location

Related Publications (4)

• Mohamed ME, Saqr A, Onyeaghala G, Remmel RP, Staley C, Dorr CR, Teigen L, Guan W, Vo D, El-Rifai R, Oetting WS, Matas AJ, Israni AK, Jacobson PA. A Mycophenolate Pharmacokinetic Study with New Insights into Enterohepatic Recirculation in Kidney Transplant Recipients. Clin Pharmacokinet. 2026 Mar;65(3):479-495. doi: 10.1007/s40262-025-01611-3. Epub 2026 Feb 6.

  PMID: 41649771 BACKGROUND

• Mohamed ME, Saqr A, Onyeaghala G, Remmel RP, Staley C, Dorr CR, Teigen L, Guan W, Madden H, Munoz J, Sanchez B, Vo D, El-Rifai R, Oetting WS, Matas AJ, Israni AK, Jacobson PA. Simultaneous Prediction of Area Under the Curves of Mycophenolic Acid and Its Metabolites and Enterohepatic Recirculation in Kidney Transplant Recipients. Ther Drug Monit. 2025 Dec 1;47(6):799-808. doi: 10.1097/FTD.0000000000001336. Epub 2025 Apr 30.

  PMID: 40315256 BACKGROUND

• Mohamed ME, Saqr A, Al-Kofahi M, Onyeaghala G, Remmel RP, Staley C, Dorr CR, Teigen L, Guan W, Madden H, Munoz J, Vo D, Sanchez B, El-Rifai R, Oetting WS, Matas AJ, Israni AK, Jacobson PA. Limited Sampling Strategies Fail to Accurately Predict Mycophenolic Acid Area Under the Curve in Kidney Transplant Recipients and the Impact of Enterohepatic Recirculation. Ther Drug Monit. 2025 Feb 1;47(1):174-182. doi: 10.1097/FTD.0000000000001248. Epub 2024 Jul 23.

  PMID: 39047238 BACKGROUND

• Khan MH, Onyeaghala GC, Rashidi A, Holtan SG, Khoruts A, Israni A, Jacobson PA, Staley C. Fecal beta-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements. Gut Microbes. 2022 Jan-Dec;14(1):2108279. doi: 10.1080/19490976.2022.2108279.

  PMID: 35921529 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

DNA from whole blood, microbiome stool and oral samples will be processed and stored

Study Officials

• Ajay Israni, MD

  University of Texas Medical Branch, Galveston

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2021
• First Posted: July 8, 2021
• Study Start: February 12, 2020
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2033
• Last Updated: August 7, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)