MSCs Infusion for Kidney Transplant

Overseen By Linda W Moore, MS,RDN,LD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Methodist Hospital Research Institute

Must be taking: Immunosuppressants

Disqualifiers: Multiple organ transplant, Hepatitis, HIV, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether infusing mesenchymal stromal stem cells (MSCs) can help kidney transplant patients reduce the immune suppression needed to maintain kidney function. It compares MSC infusion with a placebo (saline solution) to determine which better supports kidney function post-transplant. Individuals planning to receive a first-time kidney transplant from a living donor, without certain immune markers, might qualify for this study. Participants will continue to receive standard care, including medications like basiliximab and tacrolimus, to prevent kidney rejection. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancements in kidney transplant care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, all participants will receive specific medications as part of the study, including basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using mesenchymal stromal stem cells (MSCs) in kidney transplant patients is generally safe. Studies have found that patients usually tolerate MSC infusions well, with effects on the immune system similar to traditional treatments. In previous trials, patients received MSCs without major safety issues. One report mentioned a heart-related problem, but it was unclear if the MSC treatment caused it. Overall, MSC infusions appear promising and safe for kidney transplant patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for kidney transplant patients, like immunosuppressants such as Tacrolimus and Mycophenolate Mofetil, work by suppressing the immune system to prevent organ rejection. However, mesenchymal stromal stem cells (MSCs) infusion works differently. This innovative approach uses stem cells, which are believed to have regenerative and immunomodulatory properties, potentially reducing the risk of rejection and promoting healing. Researchers are excited about MSCs because they could offer a more targeted way to improve transplant outcomes, possibly reducing the side effects associated with traditional immunosuppressive drugs. This could mean better long-term health and quality of life for kidney transplant recipients.

What evidence suggests that mesenchymal stromal stem cells infusion might be an effective treatment for kidney transplant recipients?

Research has shown that mesenchymal stromal stem cells (MSCs) can benefit individuals who have undergone a kidney transplant. In this trial, some participants will receive an MSC infusion, which studies have found can enhance kidney function and reduce the risk of rejection. In certain cases, patients may even reduce or skip some anti-rejection medications. For instance, MSCs have demonstrated effectiveness similar to traditional treatments in managing the immune response post-transplant. This suggests that MSCs might help the body accept the new kidney more easily and maintain its function. ^{2 3 6 7 8}

Who Is on the Research Team?

Ahmed O Gaber, MD

Principal Investigator

Houston Methodist Physicians Organization

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 planning to receive their first kidney transplant from a living donor, with low immune risk and no history of certain antibodies or high risk for blood clots. Women must not be pregnant, agree to use two forms of birth control, and cannot breastfeed. Participants should not have HIV, active infections or cancer (except treated skin cancer), and must not have been in another study recently.

Inclusion Criteria

Planned to receive a primary kidney transplant from a living donor

Low immunologic risk defined as

No history of current or historical antidonor human leukocyte antigen (HLA) antibodies (DSA)

Exclusion Criteria

History of HIV infection

Currently participating in or has participated in an investigational drug or medical device study within 30 days or five half-lives, whichever is longer, prior to enrollment into this study

Concurrent sepsis or active bacterial infection

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mesenchymal stromal stem cells or placebo infusion at surgery and day 4 post-transplant, along with routine care including basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids

4 days

2 visits (in-person)

Safety Evaluation

Safety analyses conducted after each group of 4 subjects completes 30-90 days post-transplant to assess inflammatory response and adverse events

30-90 days

Follow-up

Participants are monitored for safety and effectiveness, including assessment of acute rejection, graft loss, or death

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Mesenchymal Stromal Stem Cells (MSCs) Infusion
• Normal Saline (Placebo) Infusion

Trial Overview The trial is testing the safety and effectiveness of mesenchymal stromal stem cells (MSCs) infusion versus saline (a placebo) in reducing the need for anti-rejection drugs after a kidney transplant. All participants will also get standard care including basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids.

How Is the Trial Designed?

Group I: Mesenchymal Stromal Stem Cells Infusion Experimental Treatment 1 Intervention

Intervention: Mesenchymal stromal stem cells infusion. This is the active investigational intervention, administered intravenously at surgery and day 4 post-transplant in a dose-escalation fashion beginning as 1x10\^6 cells for the first dose group, 2x10\^6 cells for the second dose group, or 3x10\^6 cells for the last dose group. The infusion set-up will be covered to mask the group assignment. Participants will also receive BASILIXIMAB (Simulect, for all subjects at a standard dose, 20mg reconstituted with normal saline or 5% dextrose) on the day of surgery and day 3 or 4 post-transplant administered by a member of the anesthesia team; TACROLIMUS (Prograf for maintenance therapy), MYCOPHENOLATE MOFETIL (Cellcept for maintenance therapy), and CORTICOSTEROIDS as routine care.

Group II: Placebo Infusion Placebo Group 1 Intervention

Placebo: A normal saline infusion. This is the placebo intervention to occur at surgery and day 4 post-transplant. The infusion set-up will be covered to mask the group assignment. Participants will also receive BASILIXIMAB (Simulect, for all subjects at a standard dose, 20mg reconstituted with normal saline or 5% dextrose) on the day of surgery and day 3 or 4 post-transplant administered by a member of the anesthesia team; TACROLIMUS (Prograf for maintenance therapy), MYCOPHENOLATE MOFETIL (Cellcept for maintenance therapy), and CORTICOSTEROIDS as routine care.

Who Is Running the Clinical Trial?

The Methodist Hospital Research Institute

Lead Sponsor

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

In a phase II clinical trial involving 52 patients with chronic kidney disease (CKD), the infusion of autologous CD34+ cells was found to be safe, with no adverse events reported during the treatment.

The study showed that patients receiving CD34+ cell therapy had significantly lower rates of unfavorable clinical outcomes (like dialysis or death) after one year compared to the control group, indicating potential efficacy in improving long-term outcomes for CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of intrarenal arterial autologous CD34+ cell transfusion in patients with chronic kidney disease: A randomized, open-label, controlled phase II clinical trial. Yang, CC., Sung, PH., Cheng, BC., et al.[2021]

Mesenchymal stromal cells (MSC) have shown promise in kidney transplantation, demonstrating safety and feasibility in initial clinical studies, with potential to reduce the need for immunosuppressive drugs.

Some patients treated with MSC therapy exhibited biomarkers indicating immunomodulation, leading to successful and safe complete discontinuation of immunosuppression in one case, highlighting the potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells in kidney transplantation. Casiraghi, F., Remuzzi, G.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9722440/

Autologous Mesenchymal Stem Cells for Treatment of ... Taken together, the administration of autologous MSCs in the three patients with chronic active AMR did not improve kidney graft function and ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S160061352500262X

Donor-specific mesenchymal stem cell infusion in human ... We report the results of 2 independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) ...

3. stemcellres.biomedcentral.com stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02219-7

Induction therapy with mesenchymal stromal cells in kidney ... Induction therapy with MSCs is safe and has similar immune response modulation effects to those of traditional regimens in the short term in KT recipients.

4. frontiersin.org frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1436194/full

Allogeneic mesenchymal stromal cell therapy in kidney ... In this study, we performed in-depth analyses of two cohorts (n = 20) that received third-party MSC therapy after kidney transplantation.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4391704/

Mesenchymal Stromal (Stem) Cells to Improve Solid Organ ... The use of MSC in recipients of living donor kidney transplantation (LDKT) was associated with improved graft function, reduced rejection, ability to omit ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4518147/

Safety and Efficacy Endpoints for Mesenchymal Stromal ... The first clinical trials with MSCs in renal transplantation showed safety and feasibility and displayed promising results.

7. frontierspartnerships.org frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10772/full

Autologous Mesenchymal Stem Cells for Treatment of Chronic ... The aim of this study was to evaluate the safety and efficacy of autologous MSCs in combination with standard therapy in KTRs with biopsy-proven chronic active ...

8. kidney-international.org kidney-international.org/article/S0085-2538(18)30712-9/fulltext

Infusion of third-party mesenchymal stromal cells after ... A single infusion of third-party MSC following kidney transplantation appears to be safe, with one cardiac event of unclear relationship to the ...