An interventional study of Exosomes derived from mesenchymal stromal cells (MSCs) in Premature Birth, Extreme Prematurity and Preterm Intraventricular Hemorrhage, sponsored by Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare. Not yet recruiting at 1 site in Russian Federation. Open to participants aged 1 Day to 3 Days. Per ClinicalTrials.gov, last updated 2022-09-28.
Sponsored by Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare · Not applicable, Interventional, and Prevention
To study the safety and efficacy of intranasal administration of exosomes derived from mesenchymal stromal cells on long-term neurodevelopmental outcome in extremely low birth weight infants born at gestational age 25/0-27/6 weeks.
Surviving extremely low birth weight (ELBW) infants are at risk of severe neurodevelopmental disability. Exosomes or extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) can mediate a variety of different effects, including synaptic plasticity, nutritional metabolic support, nerve regeneration, inflammatory response, anti-stress effect, cellular waste disposal, treating neurological injury, preventing hemorrhagic and ischemic brain lesions, playing an important role in health and neuroprotection in extremely premature newborns during neonatal intensive care.
The proposed blinded randomized controlled trial was designed to compare the effect of intranasal administration of exosomes on long-term neurodevelopmental outcome in ELBW infants.
ELBW infants will be randomized to receive (group 1) and not receive exosomes (control group).
Group 1 - Neonates will receive exosomes (1 dose will be obtained from a daily conditioned culture medium of 120 million MSCs) suspended in 500 µl of phosphate buffer in each nostril at 50 µl with an interval of 2-3 minutes. The therapeutic course will consist of 5 instillations with an interval of 1 days.
The primary outcome measure is the incidence of death, the incidence of survival with any of either severe intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), or brain injury on cranial ultrasound and MRI or major neurodevelopmental impairment determined at 36 months of age corrected for prematurity (where major neurodevelopmental impairment is defined as any of the following: cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Cognitive delay defined as mental developmental index (MDI) score of the Griffiths-II and Bayley Scales of Infant Development (2nd edition) \< 85, cerebral palsy, or severe visual or hearing impairment.
To investigate this outcomes and the mechanisms by which extracellular vesicles (EVs) might effect we will analyze the biomarkers of perinatal brain injury (S-100, NSE, EPO) and mRNA.
Key secondary outcomes are incidences of short term outcomes: individual components of the composite primary outcome, survival with and without major neonatal morbidity including severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC).
Safety analyses will assess the injures or damages of the nasal mucosa, allergic reaction to EVs and any adverse events after intranasal administration of EVs.
The results of this trial may help to improve the quality of life of ELBW infants and reduce long-term health care costs.
Exclusion Criteria:
ELWB newborns who will receive intranasal exosomes
Other: Exosomes derived from mesenchymal stromal cells (MSCs)
ELWB newborns who will not receive intranasal exosomes
Exosomes derived from mesenchymal stromal cells (MSCs) will be administered intranasal in ELBW infants
Occurrence and rate of dose limiting toxicity
Dose limiting toxicity consists of the following events: Death occurring within 24 hours after intranasal administration of EVs; Hypersensitivity / anaphylactic to EVs defined as any severe systemic inflammatory response syndrome with negative blood culture not consistent with the overall clinical course of the infant occurring within 72 hours after intranasal administration of EVs; Any other serious adverse event not expected in this patient population for which there is no alternative explanation but the administration of EVs, occurring within 1 week of injection.
Time frame: Up to 1 week following after intranasal administration of EVs
Rate of death
Rate of death until discharge or 40 weeks corrected gestational age, whichever comes first
Time frame: From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)
Occurrence of Other Severe Complications of Prematurity
* Blood culture-proven sepsis * Patent ductus arteriosus (treated medically or surgically) * Necrotizing enterocolitis * Isolated intestinal perforation * Retinopathy of prematurity requiring treatment * Severe intraventricular hemorrhage (≥ grade 3) * Cystic periventricular leukomalacia * Incidence and Severity of BPD, Measured as mild, moderate, or severe
Time frame: From enrollment until discharge or 40 weeks corrected gestational age (whichever occurs first)
Need for Ventilatory Support
* Time to extubation * Duration of mechanical ventilation * Duration of non-invasive positive pressure respiratory support * Duration of supplemental oxygen
Time frame: From enrollment until discharge, 40 weeks corrected gestational age, or death (whichever occurs first)
Changes in Hemodynamics
Targeted neonatal echocardiography to assess
Time frame: Time Frame: At enrollment, 48 hours following intranasal administration of EVs, 28 days of life, and 36 weeks corrected gestational age
Feasibility: Administration
Successful recruitment and administration of extracellular vesicles to 10 patients in 18 months
Time frame: Day of life 1-10
Feasibility: Recruitment Efficiency
* Proportion of potentially eligible patients that are successfully screened * Proportion of participants successfully screened who do not enroll (reason for failure to enroll will be recorded)
Time frame: Day of life 1-10
Feasibility: Recruitment Timing
* Median time from screening to enrollment * Median time from screening to extracellular vesicles
Time frame: Day of life 1-10
Feasibility: Participant Retainment
* Proportion of patients that do not complete administration of extracellular vesicles * Proportion of patients enrolled that do not undergo scheduled follow-up
Time frame: From enrollment until follow-up at 18-36 months-of-age
Griffiths-II and Bayley Scales of Infant Development (2nd edition)
Assessment of cognitive, language, and motor development. Cognitive delay defined as mental developmental index (MDI) score of the Griffiths-II and Bayley Scales of Infant Development (2nd edition) \< 85, cerebral palsy, or severe visual or hearing impairment.
Time frame: 18-36 months-of-age
Long-term Safety Follow-Up
Participant's overall health will be assessed through a questionnaire administered over the phone, once a year for 3 years
Time frame: 3 years following follow-up visit
Plan to share: No
This study is not yet recruiting, as verified in Sep 2022. You cannot join it, but the record below documents what was studied.
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Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare