UCMSC for Systemic Sclerosis

(CARE-SSc Trial)

Overseen By Marie Hudson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Marie Hudson, MD

Disqualifiers: Age < 18, Pregnancy, Neoplasms, others

Compensation: Varies

Number of Visits: 8

Duration: 3 months

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety and efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC) for the treatment of Systemic Sclerosis (SSc).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have an inadequate response or adverse events from standard therapy, which usually includes methotrexate and mycophenolate mofetil.

What data supports the effectiveness of the treatment UCMSC for Systemic Sclerosis?

Research shows that umbilical cord-derived mesenchymal stem cells (UC-MSCs) have been effective in reducing fibrosis (thickening and scarring of tissue) and autoimmune activity in animal models of systemic scleroderma, and have shown therapeutic benefits in patients with systemic lupus erythematosus, another autoimmune disease. ^{1 2 3 4 5}

Is UCMSC treatment safe for humans?

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have shown a good safety profile in clinical studies for conditions like systemic lupus erythematosus and rheumatoid arthritis, suggesting they are generally safe for human use. ^{1 2 5 6 7}

How is the UCMSC treatment different from other treatments for systemic sclerosis?

The UCMSC treatment is unique because it uses umbilical cord-derived mesenchymal stem cells, which have shown potential to reduce fibrosis (thickening and scarring of connective tissue) and modulate the immune system, offering a novel approach for systemic sclerosis, a condition with limited treatment options. ^{1 2 4 5 6}

Research Team

Marie Hudson, MD MPH

Principal Investigator

Sir Mortimer B. Davis - Jewish General Hospital

Eligibility Criteria

Adults with Systemic Sclerosis who haven't responded well to or can't tolerate standard treatments like methotrexate and mycophenolate mofetil. They should have severe disease symptoms, but not life-threatening organ damage or other serious health issues like uncontrolled infections, malnutrition, or heart failure.

Inclusion Criteria

I have severe SSc with major organ involvement or high disease activity.

I am not eligible for or do not want a stem cell transplant using my own cells.

I have been diagnosed with systemic sclerosis according to ACR/EULAR 2013 criteria.

Exclusion Criteria

Concurrent enrolment in any other protocol using an investigational drug

My BMI is under 18, indicating significant malnutrition.

You have a history of not following instructions or not taking medication as directed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusions of UCMSC or placebo at month 0 and month 3

3 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Multiple visits (in-person and virtual) at months 6, 9, and 12

Safety Monitoring

Measure of safety one month after first infusion and ongoing safety assessments

1 month

Treatment Details

Interventions

• Placebo
• UCMSC

Trial Overview The trial is testing the safety and effectiveness of Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC) compared to a placebo in treating Systemic Sclerosis. Participants will be randomly assigned to receive either UCMSC or a placebo.

Participant Groups

Group I: Two infusions of UCMSC Experimental Treatment 1 Intervention

Patients receive one intravenous infusion of UCMSC at month 0 and one intravenous infusion of UCMSC at month 3. Each experimental infusion will consist of 1 million UCMSC/kg suspended in 50 ml of PlasmaLyte A.

Group II: One infusion of UCMSC Experimental Treatment 1 Intervention

Patients receive one intravenous infusion of UCMSC at month 0 and one intravenous infusion of placebo at month 3. Each experimental infusion will consist of 1 million UCMSC/kg suspended in 50 ml of PlasmaLyte A. Each placebo infusion will consist of a similar volume of PlasmaLyte A.

Group III: Placebo infusions Placebo Group 1 Intervention

Patients receive intravenous placebo infusions at months 0 and 3. Each placebo infusion will consist of 50 ml of PlasmaLyte A.

Who Is Running the Clinical Trial?

Marie Hudson, MD

Lead Sponsor

Trials

2

Recruited

90+

University Paris 7 - Denis Diderot

Collaborator

Trials

23

Recruited

88,900+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

McGill University Health Centre/Research Institute of the McGill University Health Centre

Collaborator

Trials

476

Recruited

170,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Assistance Publique - Hôpitaux de Paris

Collaborator

Trials

3,369

Recruited

57,400,000+

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborator

Trials

389

Recruited

143,000+

Findings from Research

In a mouse model of systemic scleroderma (SSc), a single transfusion of human umbilical cord mesenchymal stem cells (UC-MSCs) significantly reduced symptoms such as skin and alveolar wall thickening, as well as lymphocyte infiltration, indicating a potential therapeutic effect.

The treatment with UC-MSCs also led to a decrease in collagen accumulation in the skin and lungs, suggesting that UC-MSCs may help prevent fibrosis and regulate the immune response in SSc.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model. Jin, X., Hou, J., Zheng, K., et al.[2022]

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 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]

Hematopoietic stem cell transplantation (HSCT) has shown promising results in treating systemic sclerosis, with a treatment-related mortality rate reduced to 2.5% in recent trials and over one-third of patients achieving sustained remission.

Current studies, including the ASTIS and SCOT trials, are exploring the efficacy of HSCT, which appears to 'reset' autoimmunity in patients, while mesenchymal stem cells from these patients show potential immunomodulatory effects comparable to healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult stem cell treatment of scleroderma. Tyndall, A., Furst, DE.[2022]

Mesenchymal stromal cells (MSC) show promising potential as a stem cell therapy for systemic sclerosis (SSc) due to their pro-angiogenic, immuno-suppressive, and anti-fibrotic properties, which could address the disease's key pathological features.

Preclinical studies in animal models of SSc have demonstrated that MSC infusion can significantly reduce skin and lung fibrosis, and early clinical trials in humans have reported safety and initial efficacy, indicating a positive direction for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells for systemic sclerosis treatment. Farge, D., Loisel, S., Lansiaux, P., et al.[2021]

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]

A study involving 64 rheumatoid arthritis patients showed that treatment with umbilical cord mesenchymal stem cells (UC-MSC) combined with traditional DMARDs led to significant improvements in disease activity and health assessments over 1 and 3 years, indicating long-term efficacy.

Safety assessments revealed no abnormalities in blood tests or organ function after UC-MSC treatment, suggesting that this therapy is safe for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study. Wang, L., Huang, S., Li, S., et al.[2023]

References

1. Korea (South) pubmed.ncbi.nlm.nih.gov

Umbilical Cord Mesenchymal Stem Cells for Inhibiting the Fibrosis and Autoimmune Development in HOCl-Induced Systemic Scleroderma Mouse Model. [2022]

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

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

Adult stem cell treatment of scleroderma. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cells for systemic sclerosis treatment. [2021]

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

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

7. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Umbilical Cord Mesenchymal Stem Cell Therapy for Rheumatoid Arthritis Patients: A Prospective Phase I/II Study. [2023]