Infusion of Allogeneic Stromal Mesenchymal Stem Cells From Wharton´s Jelly in Patients With Diffuse Cutaneous Systemic Sclerosis With Refractory Pulmonary Involvement to Treatment

NCT07542067 | Completed Phase 1

• 1 other identifier: 80-14-10-2019
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Progressive SSc is an entity with limited therapeutic alternatives and a survival rate of less than 45% within the first 3 to 5 years. The disease causes severe limitations in quality of life, ranging from functional impairment to depression. Up to 20% of patients become refractory to conventional treatment with disease-modifying anti-rheumatic drugs (DMARDs) and cyclophosphamide therapy. This condition favors progression to visceral involvement, including gastrointestinal, pulmonary, and pulmonary hypertension manifestations. The latter, considered a poor prognostic factor, increases mortality in this patient population and drastically affects quality of life. For this reason, different therapeutic options have been considered, including cell transplantation and stem cell use. Among the options studied to date are stromal mesenchymal cells derived from Wharton's jelly. These cells have been administered via intravenous infusion or direct application in various disease scenarios, ranging from vascular involvement to interstitial lung disease and pulmonary hypertension, with promising results in terms of clinical progression, quality of life improvement, and prognostic indices. This therapy has demonstrated a favorable safety profile at the time of administration and a low rate of adverse events, with self-limiting fever being the most frequent event. Based on the above and considering the possibility of offering patients without therapeutic alternatives for the disease, in addition to palliative options, an intravenous infusion of stromal mesenchymal stem cells derived from Wharton's jelly is proposed for three patients with progressive SSc refractory to conventional therapy, with pulmonary involvement due to pulmonary hypertension. Under this premise, the research question posed in this study is: What are the effects of the infusion of allogeneic mesenchymal stromal cells derived from Wharton's jelly in patients with systemic sclerosis refractory to conventional treatment with methotrexate or cyclophosphamide, in a population of three patients with severe pulmonary involvement due to pulmonary hypertension?

Conditions

Systemic Sclerosis Pulmonary; Pulmonary Hypertension; Pulmonary Fibrosis

Keywords

refractory systemic sclerosis; systemic sclerosis; pulmonary hypertension; mesenchymal stem cells

Outcome Measures

Primary Outcomes (11)

• pulmonary function

  forced vital capacity measured by forced spirometry.

  before and after 6 months treatment

• pulmonary function

  forced expiratory volume in one second. measured by forced spirometry.

  before and after 6 months treatment

• lung capacity for gas transfer

  DLCO: diffusing capacity for carbon monoxide

  before and after 6 months treatment

• submaximal excersice capacity

  Submaximal exercise capacity will be assessed using the 6-minute walk test (6MWT), performed according to American Thoracic Society (ATS) guidelines. The test measures the total distance walked in six minutes on a flat surface and is expressed in meters. This assessment is used to quantify functional limitation and prognosis associated with pulmonary hypertension. The primary outcome will be the change in distance walked between baseline and 6 months. A clinically significant improvement is defined as an increase of more than 10% from the baseline distance.

  before and after 6 months treatment

• cardiopulmonary hemodinamycs

  Pulmonary vascular resistance (PVR) will be measured by right heart catheterization and expressed in Wood units. This parameter is used to assess pulmonary vascular involvement in pulmonary hypertension, previously confirmed by standard hemodynamic criteria. The outcome will be the change in PVR between baseline and 6 months after intervention.

  before and after 6 months treatment

• cardiopulmonary hemodynamics

  Systolic pulmonary artery pressure (sPAP) will be measured by right heart catheterization and expressed in mmHg. This parameter is used to assess the severity of pulmonary hypertension. Measurements will be obtained prior to mesenchymal stromal cell infusion and repeated at 6 months after intervention. The outcome will be the change in sPAP between baseline and 6 months.

  before and after 6 months treatment

• cardiopulmonary hemodinamycs

  diastolic pulmonary artery pressure

  before and after 6 months treatment

• cardiopulmonary hemodinamycs

  right and left ventricle ejection fraction.

  before and after 6 months treatment

• quality of life and functional status

  CAMPHOR score

  before and after 6 months treatment

• quality of life and functional status

  Ssq

  before and after 6 months treatment

• parenchymatous pulmonary compromise

  high resolution chest CT

  before and after 6 months treatment

Secondary Outcomes (6)

• cutaneous fibrosis

  before and after 6 months treatment

• adverse events and security profile

  before and after 6 months treatment

• adverse events and security profile

  before and after 6 months treatment

• adverse events and security profile

  before and after 6 months treatment

• adverse events and security profile

  before and after 6 months treatment

Study Arms (1)

Historical control

OTHER

A historical control similar characteristics will be selected to compare to the treated patients.

Biological: Mesenchymal Stem Cells from Wharton´s jelly

Interventions

Mesenchymal Stem Cells from Wharton´s jelly BIOLOGICAL

intravenous infusion of Mesenchymal Stem Cells from Wharton´s jelly

Historical control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age\> 18 years and \<65 years.
• Established diagnosis of systemic sclerosis according to the criteria of the American College of Rheumatology
• SSc of poor prognosis, involving life-threatening severe visceral involvement (cardiac or pulmonary hypertension ), lack of response to conventional immunosuppressive therapy used in severe forms of the disease according to the European recommendations of EUSTAR and EBMT, relying on high doses of IV cyclophosphamide (either in monthly bolus for at least six months); or SSc with life-threatening pulmonary hypertension. Patients may or may not have pulmonary fibrosis.
• Signed informed consent.
• Presence of a consenting MSC donor
• Affiliation to social security.

You may not qualify if:

• Pregnancy or absence of appropriate contraception throughout the study.
• Pulmonary artery systolic pressure (PASP) \>75mmHg (on echocardiography or after right heart catheterization);
• \- Theorical DLCO \<30%
• Calculated creatinine clearance \<30 ml/mn/m2
• Clinical sign of a congestive heart failure refractory ;
• Left ventricular ejection fraction \<35% at myocardial scintigraphy or echocardiography;
• Chronic atrial fibrillation requiring oral anticoagulant therapy;
• Uncontrolled ventricular arrhythmia;
• Pericardial effusion with hemodynamic compromise assessed by echocardiography.
• Hepatic impairment defined as a persistent increase in transaminases or bilirubin to 3 times normal.
• Psychiatric disorders, including drug taking and alcohol abuse.
• Active neoplasia or concomitant myelodysplasia, antecedent of neoplasia.
• Bone marrow failure defined by neutropenia \<0.5 x 109 / L, thrombocytopenia \<50 x 109 / L, anemia \<8 g / dL, CD4 lymphopenia \<200 x 106 / L.
• Uncontrolled systemic hypertension.
• Uncontrolled acute or chronic infection, HIV1, 2 or HTLV-1, 2seropositivity.

Sponsors & Collaborators

• Fundación Neumologica Colombiana: lead
• CryoHoldco LATAM: collaborator
• Universidad de la Sabana: collaborator

Study Sites (1)

Clinica Universidad de La Sabana

Bogotá, Bogota D.C., 110131, Colombia

Location

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Fibrosis; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• John Londono, MD,PhD

  Universidad de la Sabana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: this study is an open-label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The administration of mesenchymal stem cells will be carried out intravenously at a concentration of 2 X 10\^6 mesenchymal cells per kilogram of patient weight. The infusions will be carried out nested at cyclophosphamide application cycles. They will be carried out ten days after each application of the cyclophosphamide schedule for each patient.

Study Record Dates

• First Submitted: May 20, 2025
• First Posted: April 21, 2026
• Study Start: May 15, 2024
• Primary Completion: June 30, 2025
• Study Completion: August 11, 2025
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

CO (1)