Mesenchymal Stem Cell Therapy for Bronchopulmonary Dysplasia in Preterm Babies

Study Overview
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Brief Summary
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Bronchopulmonary Dysplasia (BPD) is the most frequent disease related to a premature birth, 15-50% of very low birth newborns (<1500 gr.) will develop BPD. The prevalence of BPD is increasing due to the advances in neonatology, with a rise in the survival of smaller and more premature babies. The etiology of BPD is multifactorial, in which oxygen, maternal chorioamnionitis, insufficient pulmonary maturation etc. have an important role. These factors lead to a pathological development of the lung and pulmonary vessels, developing secondary Pulmonary Hypertension (PH). Nowadays there is no efficient treatment; this generates a important sanitary burden and a decrease in life quality. Multiple experimental models in mice have studied Mesenchymal Stem Cell (MSC) therapy as prevention of BPD, also recently some clinical trials have tried this therapy on premature newborns with promising results. Hypothesis: MSC therapy in patients at high risk of BPD prevents pulmonary lesions. Methods: The investigators have designed a clinical trial to evaluate the feasibility and security of MSC therapy in patients at high risk of developing BPD.

Official Title
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Clinical Trial: Security and Feasibility of Mesenchymal Stem Cell Therapy in Treatment and Prevention of Bronchopulmonary Dysplasia in Preterm Babies

Conditions
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Bronchopulmonary Dysplasia

Intervention / Treatment
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* Biological: Mesenchymal Stem Cell (MSC) therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm newborns ≤ 28 weeks gestational age Birth Weight <1250 gr. Still on of mechanical ventilation FiO2 > 0,3 at day + 14 Exclusion Criteria: Other congenital pathology (pulmonary malformations, active pulmonary bleeding, renal malformations, CHD, malformative syndromes, chromosomopathies) Severe neurological lesion. HIV infection Cardiovascular instability due to any cause 72 hours after mayor surgery Necrotizing enterocolitis grades II or higher, according to Bell classification, at the time of inclusion.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 28 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stem Cell (MSC) therapy<br>There will only be one treatment arm to evaluate the security of the treatment with MSC. | Biological: Mesenchymal Stem Cell (MSC) therapy<br>* 3 doses of 5 million MSC will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility and security of MSC therapy in very low birth weight preterm babies at risk of developing bronchopulmonary dysplasia (Number of participants with adverse events) | Number of participants with adverse events as a measure of safety and tolerability | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker analysis (IL-1beta, IL-6, IP-10, INF-gamma, TGF beta, NLRP3, RAGE, HMGB1, VEGFA, GREMLIN1, sVEGFR1, IGF, ENDOTHELIN-1, SMPD-1, SP-D, SMPD3. | biomarkers will be measured in pg/ml | 24 months | 
| Changes in the echocardiographic parameters related with PH and preterm birth, in patients treated with MSC (Number of participants with echocardiographic adverse events) | Flattening of the interventricular septum will be the main parameter (tipe I, I-II, II, II-III OR III) | 24 months | 
| Incidence of BPD and PH in very low birth weight babies treated with MSC | Diagnosed at 36 weeks of postmenstrual age | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stem cell therapy, Bronchopulmonary dysplasia, pulmonary hypertension, mesenchymal stem cells, very low weight preterm babies