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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment using cells from umbilical cords (known as UCMSC) for individuals with Systemic Sclerosis, a disease that hardens and tightens the skin and other organs. Participants will receive either one or two infusions of the UCMSC treatment or a placebo (a harmless substance with no therapeutic effect) to assess its impact on their condition. The trial seeks individuals who have had Systemic Sclerosis for two years or less, experience severe symptoms affecting their organs, and have not responded well to standard treatments like methotrexate or mycophenolate. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research has shown that treatments using cells from umbilical cords, known as Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC), are generally safe. Studies have found that patients with various conditions, including Systemic Sclerosis (SSc), tolerate these cells well, with no major safety issues reported.

In one study, patients received UCMSC infusions without experiencing serious side effects. Some minor side effects, such as mild flu-like symptoms, did occur but were not severe and typically resolved on their own.

Overall, the evidence suggests that UCMSC treatments are safe. However, ongoing research aims to confirm this and better understand any potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for systemic sclerosis, like immunosuppressants or anti-inflammatory drugs, aim to slow disease progression or manage symptoms. But UCMSC, or umbilical cord mesenchymal stem cells, offers a different approach. Researchers are excited about these treatments because UCMSC has the potential to regenerate damaged tissues and modulate the immune response, addressing the root cause rather than just the symptoms. The treatment involves infusing these stem cells directly into the bloodstream, which is a novel delivery method compared to typical oral or topical medications. This innovative approach could potentially lead to more effective and lasting results for patients with systemic sclerosis.

What evidence suggests that UCMSC might be an effective treatment for Systemic Sclerosis?

Research has shown that cells taken from umbilical cords, known as Umbilical Cord-derived Mesenchymal Stromal Cells (UCMSC), might help treat Systemic Sclerosis (SSc). These cells can influence the immune system, potentially reducing inflammation and the thickening and scarring of tissue in people with SSc. UCMSC grow well and typically do not cause strong immune reactions, allowing their use in different individuals. Previous studies in similar conditions have demonstrated that UCMSC can improve symptoms and are safe for patients. In this trial, participants will receive either one or two infusions of UCMSC or placebo infusions to evaluate their effectiveness and safety for SSc. While these results suggest that UCMSC could be helpful for SSc, further research is needed to confirm this. ^{1 2 6 7 8}

Who Is on the Research Team?

Marie Hudson, MD MPH

Principal Investigator

Sir Mortimer B. Davis - Jewish General Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04356287

NCT04356287 | Treatment With Human Umbilical Cord- ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10215673/

Umbilical-Cord-Derived Mesenchymal Stromal Cells ... Umbilical-Cord-Derived Mesenchymal Stromal Cells Modulate 26 Out of 41 T Cell Subsets from Systemic Sclerosis Patients

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8935249/

Efficacy and safety of mesenchymal stem cells in the ... The effective outcome endpoints include at least one of the six aspects of the modified parameters of disease activity in SSc patients based on ...

4. nature.com nature.com/articles/s41392-025-02313-9

Mesenchymal stem cells in treating human diseases Umbilical cord-derived MSCs (UC-MSCs) are known for their enhanced proliferation and lower immunogenicity, making them suitable for allogeneic ...

5. stemcellres.biomedcentral.com stemcellres.biomedcentral.com/articles/10.1186/s13287-021-02222-y

Human umbilical cord-derived mesenchymal stem/stromal ... Wang et al. have reported a long-term safety of UC-MSCs administered in 9 patients with refractory systemic lupus erythematosus (SLE) with no ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10921855/

Human Umbilical Cord–Derived Mesenchymal Stem Cells in ... There has yet to be a consensus on the type and dose of MSC to be used in MS. This work aims to study the safety and efficacy of two treatment ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04356287?cond=Mesenchymal%20Stem%20cell&viewType=Table&rank=9

Study Details | Treatment With Human Umbilical Cord ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S266599132100326X

Safety and preliminary efficacy of allogeneic bone marrow ... A single infusion of allogeneic bone marrow-derived mesenchymal stromal cells was safe in patients with severe diffuse systemic sclerosis.