Use of Mesenchymal Stem Cells in Pre-term Patients With Bronchopulmonary Dysplasia.

Clinical Trial to Stablish the Security of Using Allogeneic Fetal Stem Mesenchymal Cells From Umbilical Cord, Expanded in Pre-term Patients Suffering of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a disease that affects preterm newborn patients, preventing their lungs from developing properly. Allogeneic fetal stem mesenchymal cells from umbilical cord could reduce the prevalence of BPD in this patients.

Study Overview

• Status: Recruiting
• Conditions: Bronchopulmonary Dysplasia
• Intervention / Treatment: Biological: Control; Biological: Allogenic fetal mesenchymal stem cells from umbilical cord - three infusions; Biological: Allogenic fetal mesenchymal stem cells from umbilical cord - six infusions

Detailed Description

Bronchopulmonary dysplasia (BPD) is a disease that affects preterm newborn patients, preventing their lungs from developing properly, and it is a disease that is nowadays increasing due to the improvement in the survival of this patients (affecting 15-50% of them).

In the Fase I Clinical Trial, the use of allogeneic fetal stem mesenchymal cells from umbilical cord proved to be safe, with no mortality or Adverse Events reported. The Fase II Clinical Trial is based in the hypothesis that the administation of mesenchymal stem cells is not only safe but feasible and can help reducing the chance of a preterm newborn patient developing BPD.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: María Jesús del Cerro, PhD; Phone Number: 34 91 36 8000; Email: majecerro@yahoo.es
• Study Contact Backup: Name: María Álvarez, MD; Phone Number: 34 9 336 8000; Email: mery1812@hotmail.com

Study Locations

• Spain
  • La Coruña, Spain
    • Recruiting
    • Complejo Hospitalario La Coruña
    • Contact: Alejandro Dávila
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Paloma Lopez
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: Luis Arruza
  • Málaga, Spain
    • Recruiting
    • Hospital Universitario Carlos Haya
    • Contact: Tomás Sánchez Tamayo
  • Sevilla, Spain
    • Recruiting
    • Hospital Virgen del Rocío
    • Contact: Antonio Pavón Delgado
    • Principal Investigator: María José Moreno Valera
  • Valencia, Spain
    • Recruiting
    • Hospital Universitario y Politecnico La Fe
    • Contact: Máximo Vento
  • Madrid
    • Pozuelo De Alarcón, Madrid, Spain, 28223
      • Recruiting
      • Hospital Quirónsalud Madrid
      • Contact: Fernando Cabañas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Alive newborns weighing ≤ 1250 grams and GA ≤ 28 weeks, who are on mechanical ventilation with a FiO2 ≥0.3 between days 5 and 14 of life, with no immediate extubation foreseeable.

Exclusion Criteria:

• Presence of another concomitant congenital pathology at the time of inclusion: pulmonary malformations with compromised pulmonary function, active pulmonary haemorrhage, severe pulmonary hypoplasia, renal malformations with systemic compromise, congenital heart disease, polymalformative syndromes, chromosomopathies.
• Presence of refractory haemodynamic instability of any cause at the time of inclusion.
• Presence of severe neurological damage at the time of inclusion (HIV grade III or higher).
• Patients who have required major surgery in the 72 hours prior to inclusion.
• Patients who have necrotising enterocolitis (NEC) grades ≥II at the time of inclusion, according to the Bell classification.
• Patients who are children of a mother with HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control; Standard cell therapy (control group)	Biological: Control; Standard treatment
Experimental: Allogenic fetal mesenchymal stem cells from umbilical cord - three infusions; Treatment: three infusions of MSC 5x10^6/Kg	Biological: Allogenic fetal mesenchymal stem cells from umbilical cord - three infusions; 3 doses of 5 million MSC will be administered
Experimental: Allogenic fetal mesenchymal stem cells from umbilical cord - six infusions; Treatment: six infusions of MSC 5x10^6/Kg	Biological: Allogenic fetal mesenchymal stem cells from umbilical cord - six infusions; 6 doses of 5 million MSC will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Security of MSC therapy in very low birth weight preterm babies at risk of developing bronchopulmonary dysplasia	Number of patients with adverse events during the infusion time and during all study; and comorbilities due to preterm birth.	24 months
feasibility variable	Number of days of life from birth to administration of the first dose and number of days of life in successive doses.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of BPD and PH in very low birth weight babies treated with MSC	Status on week 36 of post-menstrual age	24 months
Diagnosis and stage of bronchopulmonary dysplasia on week 36 of post-menstrual age according to Jensen	(No BPD/grade 1/grade 2/garde 3)	24 months
Exitus on week 36 and 40 of post-menstrual age or at hospital discharge	(Yes/No)	24 months
Incidence of comorbidities resulting from prematurity from the time of screening to 40 weeks' EPM, hospital discharge or death.	(sepsis confirmed by blood culture, treated patent ductus arteriosus, non-pharmacological ductal closure, necrotising enterocolitis, isolated bowel perforation, intraventricular haemorrhage ≥ 2, retinopathy ≥ grade 2)	24 months
Biomarker analysis (IL-1beta, IL-6, IL8, TGF beta, TNF alfa, GM-CSF, NLRP3, RAGE, HMGB1, VEGF, HGF, GREMLIN1, sVEGFR1, SP-D, SMPD1, SMPD3, IsoPs, IsoFs, NeuroPs, NeuroFs, miRNAs).	biomarkers will be measured in pg/ml	24 months
Variations in echocardiographic parameters of pulmonary hypertension (PH) before and after mesenchymal cell therapy.	NO PH (type I less 35%), MILD PH (type I-II between 35-50%) , MODERATE PH (type II between 50-70%) and SEVERE PH ( type II-III, more than 70%)	24 months
Changes in modified respirator score during therapy and up to week 36 of port-menstrual age	0 - 13 (min- max value). Higher score means worse outcome.	24 months
Changes in Respiratory Severity Score (RSS) during therapy and up to week 36 of port-menstrual age	0-30 (min- max value). Higher score means worse outcome.	24 months
Date of hospital discharge and respiratory care at discharge.	Date of hospital discharge and respiratory care at discharge.	24 months
Need for supplemental O2 at home discharge and during follow-up (Number if patients that need supplemental O2).	Number if patients that need supplemental O2	24 months
Duration of invasive and non-invasive mechanical ventilation.	Duration of invasive and non-invasive mechanical ventilation.	24 months
Use of postnatal corticosteroids indicated	For the treatment or prevention of BPD	24 months
Respiratory readmission rates.	During the first year	24 months
Bayley Neurodevelopmental Scale at 24 months	Evaluation of cognitive developement, languaje developement and motor developement.	24 months
Date and cause of death.	Date and cause of death.	24 months

Collaborators and Investigators

• Sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
• Investigators: Principal Investigator: María Jesús del Cerro, PhD, IRYCIS. Hospital Universitario Ramón y Cajal. Madrid, Spain.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 16, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 21, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Mesenchymal stem cells; Bronchopulmonary dysplasia; Preterm newbnorn
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Lung Injury; Ventilator-Induced Lung Injury; Hyperplasia; Bronchopulmonary Dysplasia
• Other Study ID Numbers: PULMESCELL-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No