Perinatal Arterial Stroke Treated With Stromal Cells Intranasally (PASSIoN)

UMC Utrecht

Status and phase: Completed; Phase 2; Phase 1

Conditions: Perinatal Arterial Ischemic Stroke; Neonatal Stroke

Treatments: Biological: Mesenchymal Stem Cells

Study type: Interventional

Funder types: Other

Identifiers

NCT03356821

NL59265.000.16

Details and patient eligibility

About

This study will assess safety and feasibility of bone marrow-derived allogeneic MSCs, administered by the nasal route, in neonates who suffered from PAIS.

Full description

Perinatal arterial ischemic stroke (PAIS) is an important perinatal cause of long-lasting neurodevelopmental problems. Recent studies report an incidence of PAIS of 1 per 2300 full-term infants born alive. Adverse consequences of PAIS include hemiplegia, cognitive dysfunction, epilepsy and speech problems. In 50-75% of infants, neonatal stroke leads to abnormal neuromotor and -developmental outcome or epilepsy. The estimated annual mortality rate of neonatal stroke is 3.49/100,000 annually. Current treatment options for PAIS mainly focus on controlling convulsions and associated infections. There is no treatment available that leads to reduction of neonatal brain damage in this severely affected group of infants. This leads to life-long consequences of PAIS and forms a large burden for patients and society. The overall aim of this project is to meet this need by developing a cell based treatment strategy. Animal models of neonatal brain injury provide evidence for the feasibility and efficacy of intranasal mesenchymal stromal cell (MSC) application in the treatment of PAIS. Additionally, results from human trials with MSCs in the treatment of adult stroke or other pathologic conditions provide evidence that MSC treatment is safe. This project aims at making the first step towards clinical application of MSCs to treat PAIS. Successful completion of this project will provide the first evidence of the safety and feasibility of MSCs to treat brain damage in newborn infants. This study will assess safety and feasibility of bone marrow-derived allogeneic MSCs, administered by the nasal route, in neonates who suffered from PAIS.

Enrollment: 10 patients

Sex: All

Ages: Under 10 days old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• (Near-)Term infants, ≥36+0 weeks of gestation, admitted to one of the Dutch Neonatal Intensive Care Units, diagnosed with PAIS, confirmed by MRI within 3 days after presentation with clinical symptoms.
• PAIS as characterized by a predominantly unilateral ischemic lesion within the territory of the middle cerebral artery, with involvement of the corticospinal tracts, cortex, white matter and basal ganglia.
• Written informed consent from custodial parent(s).

Exclusion criteria

• Any proven or suspected congenital anomaly, chromosomal disorder, metabolic disorder.
• Presence of an infection of the central nervous system.
• No realistic prospect of survival, (e.g. severe brain injury), at the discretion of the attending physician.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Mesenchymal Stem Cells

Experimental group

Description:

All (near-)term newborns ≥36 weeks of gestation with or without clinical symptoms of PAIS but with a magnetic resonance imaging (MRI) confirmed PAIS (in the Middle Cerebral Artery region) will be eligible for this study. Following written parental consent, 10 patients will be included in our study.

Treatment:

Biological: Mesenchymal Stem Cells