Mesenchymal Stem Cells for Lupus

Recruiting at 8 trial locations

Overseen By Gary Gilkeson

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

Must be taking: Mycophenolate, Cyclophosphamide, Azathioprine

Must not be taking: Belimumab, Rituximab, Corticosteroids

Disqualifiers: Active CNS lupus, Dialysis, HIV, others

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

Compensation: Varies

Number of Visits: 13

Duration: 24 weeks

81 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of mesenchymal stem cells (MSCs) obtained from umbilical cords for the treatment of adults with systemic lupus erythematosus (SLE). The goal of this study is to determine if patients receiving an MSC infusion plus standard of care respond better than patients receiving placebo infusion plus standard of care.

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you must stop all current medications. However, you cannot change or add to your immunosuppressant regimen within 3 months of the Baseline visit, and you must not have used prednisone >0.5 mg/kg/day within 1 month of the Baseline visit. Also, you should not have received certain biologic therapies like belimumab within 2 months or rituximab within 6 months of the Baseline visit.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop all current medications, but it does mention that you should not have changes or additions to your immunosuppressant regimen within 3 months of the start, except for corticosteroids. Also, you should not have used certain medications like belimumab or rituximab within specific time frames before the trial.

What data supports the idea that Mesenchymal Stem Cells for Lupus is an effective treatment?

The available research shows that umbilical cord-derived mesenchymal stem cells (MSCs) have been tested in patients with severe and difficult-to-treat lupus. These studies found that MSCs were safe and had positive effects on the condition. For example, one study reported clinical improvements in patients who had not responded to other treatments for at least six months. Another study highlighted the potential of MSCs to help regulate the immune system, which is important in managing lupus. Overall, these findings suggest that MSCs could be a promising option for people with lupus who have not had success with other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of this treatment for lupus?

Research shows that umbilical cord-derived mesenchymal stem cells (MSCs) have been effective in treating severe and hard-to-treat cases of lupus, with studies indicating improvements in patients who did not respond to other treatments. ^{1 2 3 4 5}

What safety data is available for mesenchymal stem cell treatment in lupus?

The long-term safety of umbilical cord-derived mesenchymal stem cells (UC MSCs) for treating systemic lupus erythematosus (SLE) has been demonstrated in a 6-year follow-up study. In this study, nine patients with refractory SLE received UC MSCs infusions and were monitored for adverse events and changes in health markers. Only one patient experienced mild dizziness and warmth shortly after infusion, which resolved quickly. No other adverse events were reported, and there were no significant changes in blood counts, liver function, electrocardiogram, chest radiography, or serum tumor markers over the 6-year period. This suggests a good safety profile for UC MSCs in SLE patients. ^{1 4 5 6 7}

Is it safe to use umbilical cord-derived mesenchymal stem cells for lupus?

Research shows that umbilical cord-derived mesenchymal stem cells have a good safety profile in patients with lupus, with only mild and temporary side effects like dizziness reported. Long-term studies found no significant adverse effects over six years, indicating they are generally safe for human use. ^{1 4 5 6 7}

Is the treatment using Mesenchymal Stem Cells (MSCs) promising for lupus?

Yes, the treatment using Mesenchymal Stem Cells (MSCs) is promising for lupus. Studies show that these cells, derived from umbilical cords, have a good safety profile and can help improve symptoms in patients with severe and hard-to-treat lupus. They have shown positive effects in regulating the immune system, which is beneficial for managing lupus. ^{1 2 3 4 5}

How is the mesenchymal stem cell treatment for lupus different from other treatments?

This treatment uses umbilical cord-derived mesenchymal stem cells (MSCs), which are unique because they can potentially renew themselves and transform into different cell types, offering a novel approach for patients with severe and treatment-resistant lupus. Unlike traditional therapies, MSCs may help regulate the immune system by balancing specific immune cells, providing a new option for those who haven't responded to standard treatments. ^{1 2 3 4 5}

Research Team

Gary S. Gilkeson, MD

Principal Investigator

Medical University of South Carolina

Diane L. Kamen, MD, MSCR

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

Adults aged 18-65 with active Systemic Lupus Erythematosus (SLE), evidenced by specific antibody tests and a minimum SLEDAI score, can join. They must have been on standard therapy for lupus nephritis if present. Exclusions include severe kidney issues, certain infections like HIV or TB, recent cancer (except some skin cancers/cervical carcinoma in situ), pregnancy/breastfeeding without contraception use, major organ transplants, unstable medical conditions, high steroid use recently or changes in immunosuppressants.

Inclusion Criteria

Historical presence of at least 4 of 11 of the ACR Classification Criteria

My lupus is active despite treatment, as shown by specific lupus activity scores.

I have completed 6 months of treatment for kidney inflammation.

Exclusion Criteria

I have lupus affecting my kidneys and need dialysis.

I haven't had cancer in the last 5 years, except for certain skin cancers or cervical pre-cancer.

My lupus affects my brain and thinking.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a low or high dose of mesenchymal stem cells or placebo through a single IV infusion, along with standard of care

24 weeks

1 visit (in-person) for infusion, regular follow-up visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at Weeks 12, 24, and 52

28 weeks

Regular follow-up visits at Weeks 12, 24, and 52

Treatment Details

Interventions

• High Dose Mesenchymal Stem Cells (MSCs)
• Low Dose Mesenchymal Stem Cells (MSCs)
• Placebo Infusion

Trial Overview The trial is testing the effectiveness of two different doses of Mesenchymal Stem Cells from umbilical cords against a placebo. All participants will continue their standard lupus treatments. The main goal is to see if those who get the stem cells show more improvement than those who get the placebo.

Participant Groups

Group I: Low Dose Mesenchymal Stem Cells (MSCs) Experimental Treatment 1 Intervention

Mesenchymal Stem Cells (MSCs) 1 x 10\^6 cells/kg in Plasma-Lyte A solution

Group II: High Dose Mesenchymal Stem Cells (MSCs) Experimental Treatment 1 Intervention

Mesenchymal Stem Cells MSCs 5 x 10\^6 cells/kg in Plasma-Lyte A solution

Group III: Plasma Lyte A Solution Placebo Group 1 Intervention

Placebo Infusion (Plasma-Lyte A solution only)

High Dose Mesenchymal Stem Cells (MSCs) is already approved in China, United States for the following indications:

Approved in China as Mesenchymal Stem Cells for:

• Systemic Lupus Erythematosus (SLE)
• Lupus Nephritis

Approved in United States as Umbilical Cord-Derived Mesenchymal Stem Cells for:

• Refractory Systemic Lupus Erythematosus (SLE)

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

Findings from Research

In a multicenter clinical trial involving 40 patients with active and refractory systemic lupus erythematosus (SLE), umbilical cord-derived mesenchymal stem cell transplantation (UC-MSCT) demonstrated a high safety profile with no transplantation-related adverse events and an overall survival rate of 92.5%.

The treatment resulted in significant clinical improvements, with 32.5% of patients achieving a major clinical response and 27.5% achieving a partial clinical response, although some patients experienced disease relapse after 6 months, suggesting the need for potential repeat treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Wang, D., Li, J., Zhang, Y., et al.[2022]

In a phase I trial involving six women with refractory lupus, 83.3% achieved significant clinical improvement after receiving umbilical cord-derived mesenchymal stromal cells (MSCs), indicating potential efficacy of this treatment.

The MSC infusions were found to be very safe, with minimal adverse events, and were associated with notable changes in B cell populations and GARP-TGFβ complexes, suggesting a novel mechanism of action in modulating the immune response in lupus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunological effects and clinical response in a phase I trial of umbilical cord mesenchymal stromal cells in patients with treatment refractory SLE. Kamen, DL., Wallace, C., Li, Z., et al.[2022]

In a study of 37 patients with refractory systemic lupus erythematosus (SLE), those receiving umbilical cord mesenchymal stem cells (UC-MSCs) in addition to standard treatments showed significant improvements in key clinical markers, such as decreased urinary protein excretion and improved serum albumin levels, compared to the control group.

The UC-MSCs group also had a lower rate of positive anti-dsDNA antibodies and recurrence of symptoms, indicating enhanced efficacy of the treatment without any observed complications related to the stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic effects of umbilical cord mesenchymal stem cells transplantation on systemic lupus erythematosus]. Yang, GX., Pan, LP., Zhou, QY., et al.[2018]

In a study involving 16 patients with severe systemic lupus erythematosus (SLE) who did not respond to standard treatments, umbilical cord-derived mesenchymal stem cell transplantation (UC MSCT) led to significant improvements in disease activity and serological markers over a median follow-up of 8.25 months.

The treatment was safe, with no treatment-related deaths or recurrences of disease, and was associated with an increase in regulatory T cells and a balanced cytokine profile, suggesting a potential mechanism for its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Sun, L., Wang, D., Liang, J., et al.[2022]

In a study involving 30 patients with systemic lupus erythematosus (SLE) who received umbilical cord-derived mesenchymal stem cells (UC MSCs), the treatment led to an increase in regulatory T cells (Treg) and a decrease in T helper 17 (Th17) cells over a 12-month period, indicating a potential immunoregulatory effect.

The mechanism of action for UC MSCs involves the regulation of cytokines such as TGF-β and prostaglandin E2 (PGE2), which were found to be crucial for the observed changes in Treg and Th17 cell populations, suggesting a targeted approach for managing SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. Wang, D., Huang, S., Yuan, X., et al.[2022]

In a long-term study involving 9 patients with refractory systemic lupus erythematosus (SLE), allogeneic umbilical cord mesenchymal stem cells (UC MSCs) showed a good safety profile, with only one patient experiencing mild dizziness after infusion, which quickly resolved.

After 6 years of follow-up, there were no significant adverse events or changes in blood counts, liver function, or tumor marker levels, indicating that UC MSC transplantation is safe for SLE patients who do not respond to conventional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study. Wang, D., Niu, L., Feng, X., et al.[2022]

Transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in early-stage lupus model mice significantly reduced harmful B cell populations and inflammatory factors, suggesting a potential therapeutic effect for mild systemic lupus erythematosus (SLE).

The treatment also alleviated kidney injury by decreasing inflammatory cell infiltration and antibody deposition in the kidneys, indicating that hUC-MSCs may offer a new strategy for managing SLE without affecting overall body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages. Guo, F., Pan, Q., Chen, T., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Safety, immunological effects and clinical response in a phase I trial of umbilical cord mesenchymal stromal cells in patients with treatment refractory SLE. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Therapeutic effects of umbilical cord mesenchymal stem cells transplantation on systemic lupus erythematosus]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. [2022]

5. China pubmed.ncbi.nlm.nih.gov

The regulation of the Treg/Th17 balance by mesenchymal stem cells in human systemic lupus erythematosus. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages. [2023]