Reduced Immunosuppression in Older Renal Transplant Recipients With Trugraf®/TRAC Monitoring (RIOT Trial): A Prospective, Randomized, Multicenter Trial. (RIOT)

Reduced Immunosuppression in Older Renal Transplant Recipients With Trugraf® Monitoring (RIOT Trial): A Prospective, Randomized, Multicenter Trial.

The purpose of this research is to determine the safety and efficacy of withdrawing MMF (Mycophenolate Mofetil) in kidney transplant recipients who are 55 years or older at the time of receiving a kidney transplant. We are comparing them to patients who receive the standard of care Mycophenolate Mofetil.

Study Overview

• Status: Recruiting
• Conditions: Kidney Transplantation; Mycophenolate Mofetil
• Intervention / Treatment: Drug: Mycophenolate Mofetil (MMF) Maintenance Group; Drug: Mycophenolate Mofetil (MMF) Withdrawal Group

Detailed Description

Participation will be two years and it involves blood collection, collection of medical information and images from standard of care kidney biopsies. Subjects will be asked to complete questionnaires for the study at 12 and 24 months after kidney transplant. The research blood tests that are being collected for the study are called Trugraf®, Eurofins TRAC®, Trac-ID and Immunophenotyping and Single Cell RNA -sequencing. The principal investigator is using this test to see if they can predict and monitor rejection and viral infections in our kidney transplant patients. Immunophenotyping and single cell RNA sequencing tests are being done to identify unique gene expression profiles and their functions in different immune cells.

At the time of the 4 month standard of care follow up visit, if participants have not experienced any rejection episodes or formed any donor specific antibodies (dnDSA) and are still eligible, randomization will occur. Participants will be put into 1 of 2 groups: Mycophenolate Mofetil Maintenance group where the subject would continue on current medication, or the subject will be placed into the MMF Withdrawal group which means they would slowly be withdrawn from this medication. If the subject is not eligible to be randomized, they will remain in the study and placed into the Non-Randomized group and continue to have study related visits and procedures like the MMF Maintenance group.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nong Yowe Braaten, LPN; Phone Number: 507-266-6893; Email: braaten.nong@mayo.edu
• Study Contact Backup: Name: Esma Kesik, M.D.; Phone Number: 507-284-4562; Email: kesik.esma@mayo.edu

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Sami Alasfar, MD
      • Contact: Xavier Lopez; Phone Number: 480-574-4258; Email: lopez.xavier@mayo.edu
      • Contact: Fady Khorany; Phone Number: 480-574-1323; Email: khorany.fady@mayo.edu
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic
      • Contact: David A. Legaspi; Phone Number: 904-953-4990; Email: legaspi.david@mayo.edu
      • Contact: Jessica Toukmehji; Phone Number: 904-953-8722; Email: toukmehji.jessica@mayo.edu
      • Principal Investigator: Hani M Wadei, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Mark D Stegall, M.D.
      • Contact: Nong Yowe Braaten, L.P.N.; Phone Number: 507-266-6893; Email: braaten.nong@mayo.edu
      • Contact: Esma Kesik, M.D; Phone Number: 507-284-4562; Email: kesik.esma@mayo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Solitary kidney transplant recipient >55 years of age. At most 1 prior solitary kidney transplant.
• No other solid organ transplant though recipients of autologous stem cell transplants are eligible.
• HIV negative.
• Subjects must be on tacrolimus and mycophenolate mofetil or Myfortic at the time of consent. Prednisone at the time of consent is optional and is per local standard of care. Patients randomized to MMF withdrawal will be placed on prednisone 5mg/d at 4 months. Use of other immunosuppression medications for maintenance (cyclosporine, azathioprine, belatacept, sirolimus) is excluded.

Exclusion Criteria:

Time of Transplant Exclusion Criteria:

• The results of the most recent DSA testing indicate DSA with an MFI >2000.

• The results of the most recent cPRA testing indicate cPRA is above >80% (based on MFI >2000).

  4-Month Exclusion Criteria:

• Acute rejection episode either clinical or on biopsy (greater than borderline). Subjects must not experience any type of rejection episodes from the time of transplant and must not show any signs of rejection (Cellular or Antibody mediated rejection, excluding borderline) at their 4-month biopsy (If obtained per standard of care). Subjects experiencing rejection will not be eligible for randomization and MMF withdrawal.
• De novo DSA
• Subjects who are not on tacrolimus at the time of randomization will be placed in the non-randomized group.
• Subjects who at the time of or prior to randomization were maintained on mycophenolate mofetil or Myfortic and have had their medication held or temporarily discontinued due to clinical indications (toxicity to the medication, polyoma virus infections, cancer, etc.) remain eligible for randomization.
• Has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings which, in the opinion of the investigator, would make study participation not in the participants best interest (e.g., compromise the well-being) or that could prevent, or limit the protocol-specified assessment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Non-Randomized Group; Individuals who do not meet eligibility for randomization will continue in the study and continue to follow study related visits. Individuals will continue with their current immunosuppression medication.
Active Comparator: MMF Maintenance Group; Individuals randomized to the MMF Maintenance Group will not be withdrawn from their MMF and will continue to follow their standard of care immunosuppression medications.	Drug: Mycophenolate Mofetil (MMF) Maintenance Group; Mycophenolate Mofetil (MMF), administered orally as standard of care post kidney transplant as part of their immunosuppression regimen. Maintenance in Immunosuppression medication.; Other Names: CellCept
Experimental: MMF Withdrawal Group; Individuals randomized to the MMF Maintenance Group will be withdrawn from their MMF immunosuppression medication from Month 4 to Month 10 post-transplant.	Drug: Mycophenolate Mofetil (MMF) Withdrawal Group; Mycophenolate Mofetil (MMF), administered orally as standard of care post kidney transplant as part of their immunosuppression regimen. Withdrawal of MMF immunosuppression medication.; Other Names: CellCept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Rejection	Total number of subjects to experience acute rejection of the renal transplant	4 to 24 months post transplant.
Patient Deaths	Total number of subject deaths from 4-24 months post transplant.	4 to 24 months post transplant.
Graft Failure	Total number of subjects to experience graft failure from the renal transplant	4 to 24 months post transplant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious Adverse Events (SAE)	The total number of subjects to experience SAE's. Defined as subjects experience any one of the following: acute cellular or antibody medicated rejection, borderline rejection or dnDSA (De novo donor-specific antibodies)	1 and 2 years post transplant.
eGFR (estimated glomerular filtration rate)	eGFR is calculated from a lab blood test using a formula that measures the level of creatinine. In this test a higher number is better. An eGFR value lower than 60 is a sign that the kidneys may not be working properly. Measured as mL/min/1	2 years post transplant
Single antigen beads (SAB) for donor-specific antibodies	Single antigen bead (SAB) assay is a lab blood test used to detect human leukocyte antigen antibodies (HLA) and assessing the immunological risk for organ transplant. For HLA-DRβ1/3/4/5 the single molecule mismatches can range from 0-22 and for HLA-DQα1/β1 the single molecule mismatches range from 0-31. Measured as pg/mL.	Baseline, 1 year post transplant and 2 years post transplant
BANFF scores	The Banff 2018 classification involves scoring numerous characteristics of renal biopsy specimens. The scores can take values of 0, 1, 2, or 3 for each characteristic, indicating increasing severity of disease as the scores increase.	2 years post transplant.
Absolute lymphocyte counts	An absolute lymphocytes count is determined by multiplying the total number of white blood cells by the percentage of white blood cells that are lymphocytes. The normal range for lymphocytes is between 800 and 5000 (0.8-5.0) lymphocytes per mL of blood. A normal lymphocytes percentage is 18-45% of total white blood cells. Measured as cells per microliter (cells/µL)	1 year post transplant and 2 years post transplant
Transplant Related Symptom (CIRS) Questionnaire	The CIRS questionnaire is a 36-item questionnaire that contains statements that rate transplant symptoms on a scale of 1(None) to 5 (Very Severe). Total scores range from 36-180, lower scores indicate less severe symptoms, higher scores indicate more severe symptoms.	2 years post transplant.
Albumin/Creatinine Ratio (Microalbumin) Urine	The urine albumin-creatinine ratio (uACR) test measures the amount of two different substances in urine - albumin (a protein) and creatinine. A value of 30 or higher suggests a higher risk for kidney failure. Measured as mg/g	2 years post transplant

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: Transplant Genomics, Inc.; Eurofins
• Investigators: Principal Investigator: Mark D Stegall, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2025
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): March 31, 2031

Study Registration Dates

• First Submitted: August 21, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 23, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Kidney Transplant
• Additional Relevant MeSH Terms: Organic Chemicals; Fatty Acids; Lipids; Acids, Acyclic; Carboxylic Acids; Caproates; Mycophenolic Acid
• Other Study ID Numbers: 24-002574

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Plans for data sharing may include data summaries consisting of tables, charts, and figures. Data included will be anonymous and could include demographics, clinical data collected during the study and correlations with Trugraf and Viracor results. Aggregate data for demographics, Subject ID, etc. will only be shared for involving of milestones.

The clinical study final report and paper submitted for any publication will also be submitted.

• IPD Sharing Time Frame: Ongoing data analysis will be performed throughout the study. After completion of all study subjects' visits, final data will be cleaned, reviewed and analyzed by study staff. A clinical summary report would be expected to be delivered to TGI-Eurofins within a year of subject completed visits. We would expect a paper to be written and submitted to a journal for review and acceptance within 2 years of final study completion.
• IPD Sharing Access Criteria: Data sharing with TGI- Eurofins and study staff.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No