What side effects are associated with this type of intervention?

Common treatments for kidney failure that involve inhibition of the RhoA and mTOR pathways, such as Fingolimod, often include immunosuppressive agents like calcineurin inhibitors (e.g., cyclosporine, tacrolimus) and mTOR inhibitors (e.g., sirolimus, everolimus). Known side effects of these treatments can include increased risk of infections, nephrotoxicity, hypertension, hyperlipidemia, and diabetes. Specific to mTOR inhibitors, patients may experience mouth ulcers, delayed wound healing, and pneumonitis. Fingolimod itself may cause bradycardia, macular edema, and elevated liver enzymes.

What prior FDA approvals exist?

FDA-approved treatments for kidney failure, particularly in the context of kidney transplantation, include mechanistic target of rapamycin (mTOR) inhibitors such as sirolimus and everolimus. These drugs are used to prevent organ rejection by inhibiting the mTOR pathway, which is crucial for cell growth and proliferation. Fingolimod, which is being studied for its potential to inhibit both the RhoA and mTOR pathways, aims to reduce interstitial fibrosis and tubular atrophy in transplanted kidneys, potentially improving graft survival and function.

What other types of research exist?

Promising novel alternatives to Fingolimod for kidney failure patients in 2024 include: <ol> <li>TRF-budesonide: This drug has shown efficacy in reducing proteinuria and stabilizing eGFR in patients with IgA nephropathy, although it has a high rate of glucocorticoid-related adverse events.</li> <li></li> </ol> Calcineurin Inhibitors (CNIs) such as cyclosporine and tacrolimus: These have been investigated for their potential to achieve higher rates of complete remission of proteinuria in combination with glucocorticoids. 3. Emerging angiogenesis inhibitors and HIF-2 antagonists: These target key pathways involved in kidney damage and have shown potential in clinical trials for renal cell carcinoma, which may translate to benefits in preventing kidney failure.

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Immunosuppressant

Fingolimod for Kidney Transplant Rejection

Phase 2

Waitlist Available

Research Sponsored by The Methodist Hospital Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Receiving a first or second kidney transplant

Able to take oral medication

Must not have

Diagnosed with severe liver disease, including abnormal liver enzymes or total bilirubin greater than three times upper limit of normal

Known macular degeneration

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 3 months after kidney transplant, 1 year after kidney transplant

Awards & highlights

All Individual Drugs Already Approved

Summary

This trial tests if fingolimod can help new kidney transplant patients by preventing kidney damage and improving transplant success. Fingolimod works by blocking harmful pathways in the body. The study aims to see if this treatment is safe and effective over time. Fingolimod has been used in multiple sclerosis treatment and is known for its immunomodulating effects, but it has significant potential side effects.

Who is the study for?

Adults aged 18-65 who are receiving their first or second kidney transplant can join this trial. They must be able to take oral medication, have a low level of antibodies, and agree to use two forms of birth control if applicable. People with heart issues, severe liver disease, recent strokes, certain infections or cancers (except some skin cancers), or those on anticoagulants cannot participate.

What is being tested?

The trial is testing whether Fingolimod added to standard immunosuppression can prevent damage in transplanted kidneys by stopping fibrosis from developing. Participants will either receive Fingolimod or a placebo without knowing which one they're getting.

What are the potential side effects?

Fingolimod may cause side effects like slow heart rate, increased risk of infections due to its immune system effects, potential liver problems, and possibly vision issues such as macular degeneration.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am getting my first or second kidney transplant.

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I can take medicine by mouth.

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I am between 18 and 65 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe liver disease with high liver enzyme or bilirubin levels.

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I have been diagnosed with macular degeneration.

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I am allergic to Gilenya® or its ingredients like fingolimod.

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I have been taking ketoconazole for more than 2 weeks.

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I am a woman able to have children and am currently breastfeeding.

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I have a blood clotting disorder or need long-term blood thinners that would make biopsies difficult.

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I have a serious heart rhythm problem or take specific heart rhythm medications.

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I have been diagnosed with a sudden lung condition.

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I have had an organ transplant, but it was not a kidney.

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I haven't had any major heart problems in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 3 months after kidney transplant, 1 year after kidney transplant

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 3 months after kidney transplant, 1 year after kidney transplant

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 3 months after kidney transplant, 1 year after kidney transplant for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Emergent and Adverse Events

Secondary study objectives

BMP-7 Protein Biomarker

Biopsy-Proven Acute Rejection

Causes of End-Stage Renal Disease

+10 more

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: FingolimodActive Control1 Intervention

Participants will take a 0.5 mg fingolimod capsule each day for 3 months. The fingolimod capsule will be placed inside an opaque closed gelatin capsule without transformation of the manufacteror's fingolimod capsule. The fingolimod blinded product and the placebo capsule will be identical in size, color, appearance, and weight.

Group II: PlaceboPlacebo Group1 Intervention

Participants will take a placebo capsule daily for 3 months. Placebo will be methylcellulose encapsulated into an opaque closed gelatin capsule for blinding. Capsules will be placed in a labeled bottle, with the contents only identifiable by a code on the package label and only the compounding pharmacy and the unblinded pharmacist at Houston Methodist Investigational Drug Service will know the code definition.

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for kidney failure often target specific molecular pathways to prevent further damage and promote recovery. Fingolimod, for example, inhibits the RhoA and mTOR pathways, which are involved in cellular growth, fibrosis, and inflammation. By blocking these pathways, Fingolimod aims to reduce structural damage and fibrosis in the kidneys, potentially improving graft survival and function. This is crucial for kidney failure patients as it addresses the underlying mechanisms of disease progression, offering a targeted approach to preserve kidney function and delay the need for dialysis or transplantation.

Molecular targeting of renal inflammation using drug delivery technology to inhibit NF-κB improves renal recovery in chronic kidney disease.New targets for treatment of diabetic nephropathy: what we have learned from animal models.