Infusion of Allogeneic Mesenchymal Stem Cells in Patients With Diffuse Cutaneous Systemic Sclerosis With Refractory Pulmonary Involvement

Pulmonary Hypertension Clinical Trial

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

Status Available

Clinical Trial Summary

Progressive SSc is an entity with limited therapeutic alternatives and with asurvival rate of less than 45% in the first 3 to 5 years. The disease causessevere limitation in quality of life ranging from functional limitation to depression. Up to 20% of patients will be refractory to conventional treatment with diseasemodifying anti-rheumatic drugs (DMARDs) and cyclophosphamide therapy.This favors the progression to visceral involvement including gastrointestinal,lung and pulmonary hypertension. The latter being a poor prognostic factor,increases mortality in this group of patients and drastically affects their qualityof life. For this reason, different therapeutic options have been considered including cell transplantation and Stem Cell use. Among the options that have been studied so far are stromal mesenchymal cells from Wharton ́s jelly. These have been used in intravenous infusion or direct application in different disease scenarios ranging from vascular involvement to interstitial lung involvement and cases of pulmonary hypertension, with promising results in terms of clinical progression,improvement in quality of life and prognostic indices. This therapy has proven to have a significant margin of safety at the time of administration and a low rate of adverse events, a self-limiting fever as the most frequent event. Based on the above and considering the possibility of offering patients without therapeutic alternatives to their disease in addition to palliative options, an intravenous infusion of stromal mesenchymal stem cells from Wharton ́s jellyis proposed for three patients with progressive SSc refractory to conventional therapy with pulmonary involvement due to pulmonary hypertension.

Under this premise the question posed in our work is; What are the effects of the infusion of allogeneic mesenchymal stromal cells from Wharton ́s jellyin 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.

Clinical Trial Description

This study aims to evaluate the therapeutic effects of allogeneic mesenchymal stromal cell infusion as a treatment in patients with systemic sclerosis refractoryto conventional therapy. The group of patients will be collected from the database of families of Stem Regenerative Medicine according to the inclusion and exclusion criteria and verified in the academic committee.

The administration will be intravenously, with 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 ten days after each application of the cyclophosphamide schedule for each patient. To assess safety and therapeutic effects, the occurrence of any adverse event will be described from start of infusion until the conclusion of the trial in six months.

To assess the response, a pre-infusion and sixth-month post-infusion instrument will be applied that includes clinical variables, paraclinical and hemodynamic tests to evaluate skin involvement using the modified RODNAN score, changes in nail capillaroscopy, lung function and structural involvement by high-resolution chest tomography (hrCT), diffusion capacity for carbon monoxide (DLCO) and a 6-minute walk. As part of the cardiovascular assessment, cerebral natriuretic peptide (BNP), transthoracic echocardiogramwill be performed; The Cambridge Pulmonary Hypertension Outcome Review(CAMPHOR) and Sysq will be used as tools for the assessment of pulmonary hypertension. A comparison of these tests before initiation of therapy and after completion of 24 weeks of infusion scheme should be performed. ;

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Fibrosis
• Pulmonary Hypertension
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis Pulmonary

• NCT number: NCT04432545
• Study type: Expanded Access
• Source: Universidad de la Sabana
• Contact: John Londono, MD,PhD
• Phone: +573187114885
• Email: john.londono@unisabana.edu.co
• Status: Available