Reduced Immunosuppression for Older Kidney Transplant Recipients

(RIOT Trial)

Recruiting at 2 trial locations

Overseen By Nong Yowe Braaten

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Mayo Clinic

Must not be taking: MMF

Disqualifiers: Acute rejection, DSA MFI >500, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

350 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of reducing Mycophenolate Mofetil (MMF), an immunosuppressant, in individuals aged 55 or older who have received a kidney transplant. Researchers will compare patients who stop taking MMF with those who continue to determine if reducing the medication is advisable. The trial targets individuals who have had a single kidney transplant without experiencing organ rejection. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader patient population.

Will I have to stop taking my current medications?

The trial involves withdrawing Mycophenolate Mofetil (MMF) for some participants, but it does not specify if you need to stop other medications. It's best to discuss your current medications with the trial team.

What is the safety track record for Mycophenolate Mofetil (MMF)?

Research shows that Mycophenolate Mofetil (MMF) is generally safe for kidney transplant recipients. Studies have found that MMF lowers the risk of the body rejecting the new kidney, which is crucial for transplant patients.

Evidence also suggests that reducing the dose of MMF can prevent infections without increasing the risk of kidney rejection. Nearly half of kidney transplant patients were on a lower dose of MMF after one year, and this number grew over time. Importantly, their health outcomes remained the same whether on a low or standard dose.

However, no high-quality studies have determined the best long-term dose for MMF, leaving some questions about the safest dose over time unanswered.

In summary, MMF is generally well-tolerated, and lowering the dose might help avoid some side effects. It is important to discuss any treatment decisions with a healthcare provider. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for kidney transplant recipients involve long-term immunosuppression to prevent organ rejection, typically using drugs like Mycophenolate Mofetil (MMF). However, researchers are excited about exploring reduced immunosuppression, especially for older patients, because it could minimize long-term side effects and improve quality of life. The idea is to reduce dependency on MMF, a common immunosuppressant, and observe if patients can still maintain transplant health with less medication. This approach could potentially lead to fewer complications like infections or cancers, which are risks associated with prolonged immunosuppression.

What evidence suggests that withdrawing MMF could be effective for older kidney transplant recipients?

Research has shown that Mycophenolate Mofetil (MMF) lowers the risk of kidney rejection in transplant patients. Studies have found that MMF improves the survival of the transplanted kidney by preventing rejection episodes. In this trial, participants in the MMF Maintenance Group will continue their MMF treatment to maintain transplant health. Meanwhile, those in the MMF Withdrawal Group will gradually stop MMF from Month 4 to Month 10 post-transplant to assess the effects of reduced immunosuppression. Overall, MMF is well-regarded for helping kidney transplant recipients maintain their new kidney's function over time. ^{1 2 6 7 8}

Who Is on the Research Team?

Mark Stegall, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for kidney transplant recipients aged 55 or older. It's not specified who can't join, but typically those with additional serious health issues or incompatible medications would be excluded.

Inclusion Criteria

HIV negative

I have not had any organ transplants, but I may have had a stem cell transplant using my own cells.

I am over 55 and have had one or two kidney transplants.

Exclusion Criteria

This criterion does not apply to me as it lacks specific information.

De novo DSA

4-Month Exclusion Criteria:

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment

Participants receive standard immunosuppression medication including Mycophenolate Mofetil

4 months

Regular visits for monitoring and standard of care kidney biopsy

Randomization and Treatment Adjustment

Participants are randomized into either MMF Maintenance or MMF Withdrawal groups, or continue in the Non-Randomized group

6 months

Regular visits for monitoring and adjustment of medication

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of graft function and rejection

2 years

Visits at 12 and 24 months post-transplant for questionnaires and assessments

What Are the Treatments Tested in This Trial?

Interventions

• Mycophenolate Mofetil (MMF)

Trial Overview The study is testing the safety and effectiveness of stopping Mycophenolate Mofetil (MMF), a common post-transplant medication, compared to continuing it as standard care in older kidney transplant patients.

How Is the Trial Designed?

Group I: MMF Withdrawal Group Experimental Treatment 1 Intervention

Individuals randomized to the MMF Maintenance Group will be withdrawn from their MMF immunosuppression medication from Month 4 to Month 10 post-transplant.

Group II: MMF Maintenance Group Active Control 1 Intervention

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.

Group III: Non-Randomized Group Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Transplant Genomics, Inc.

Industry Sponsor

Trials

16

Recruited

4,800+

Eurofins

Industry Sponsor

Trials

20

Recruited

8,100+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2697521/

Mycophenolate mofetil: safety and efficacy in the ... Clinical trials in kidney transplant recipients have shown the efficacy of MMF in reducing the incidence and severity of acute rejection episodes.

2. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2025.13790/full

Indications and Long-Term Outcomes of Using ... Mycophenolate mofetil monotherapy (MMF-MT) is currently considered a good measure in recipients with chronic kidney disease (CKD) and other CNI-related adverse ...

3. journals.lww.com journals.lww.com/transplantjournal/abstract/2018/07001/correlation_between_mycophenolate_dosage_and.949.aspx

Correlation between Mycophenolate Dosage and ... Mycophenolate mofetil (MMF) is effective in improvement of graft survival and prevention of acute rejection after kidney transplantation.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0041134524002811

Safety and Efficacy of Mycophenolate Mofetil Associated ... TAC+MMF was associated with a lower risk of rejection than MMF monotherapy (RD: -0.24; 95%CI -0.46; -0.02). Comparing TAC+MMF with the other regimens, no ...

5. nature.com nature.com/articles/s41598-020-76379-6

Initial mycophenolate dose in tacrolimus treated renal ... Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to ...

6. journals.lww.com journals.lww.com/transplantationdirect/fulltext/2024/09000/safety_and_efficacy_of_a_preemptive_mycophenolate.14.aspx

Safety and Efficacy of a Preemptive Mycophenolate Mofetil... There are no high-quality data to guide long-term mycophenolate mofetil (MMF) dosing in kidney transplant recipients (KTRs) to balance the long-term risks of ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0041134524005748

Physician-Directed Mycophenolate Mofetil Dose Reduction ... Almost 50% of KT recipients were on low dose MMF at 1 year and this percentage increased by 5 years. We did not observe a difference in outcomes between those ...

8. leoriella.com leoriella.com/safety-and-efficacy-of-a-preemptive-mycophenolate-mofetil-dose-reduction-strategy-in-kidney-transplant-recipients/

Safety and Efficacy of a Preemptive Mycophenolate Mofetil ... Conclusions: Preemptive MMF dose reduction in KTRs may be an effective strategy to prevent infections without increasing the risk of allograft rejection.