| Registry | NCT07831746, acronym iSTOP-CP |
|---|---|
| Status | Not yet recruiting |
| Phase | Phase 2 / Phase 3 |
| Study type | Interventional; randomized, parallel, masking: quadruple, treatment |
| Enrollment | 162 (Estimated) |
| Sponsor | UMC Utrecht (Other) |
| Conditions | Perinatal Arterial Ischemic Stroke, Perinatal Asphyxia, Hypoxic-Ischemic Brain Injury, PAIS, HIE - Hypoxic - Ischemic Encephalopathy |
| Interventions | MSC, marrow, Placebo (Drug) |
| Dates | start 2027-04-01 (estimated), primary completion 2032-09-01 (estimated), completion 2032-09-01 (estimated), first posted 2026-09-21, last updated 2026-09-21 |
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All trials for Perinatal Arterial Ischemic Stroke All trials for Perinatal Asphyxia All trials of MSC, marrow All trials of Placebo
Hypoxic-ischemic brain injury (HIBI) is a leading cause of death and lifelong disability in near-term and term infants, most often caused by perinatal arterial ischemic stroke (PAIS, incidence approximately 1:5000 live births) or perinatal asphyxia (PA, incidence 1-2:1000 live births). No treatment currently exists to repair or limit HIBI, and many affected infants go on to develop cerebral palsy, cognitive impairment, epilepsy, or visual or hearing deficits. Intranasally administered bone marrow-derived mesenchymal stromal cells (IN-MSC) are a candidate regenerative therapy for HIBI. Preclinical studies show that IN-MSC migrate to injured brain regions, dampen neuroinflammation, and stimulate endogenous neural repair, improving both structural and functional outcomes in animal models of HIBI. A first-in-human phase I trial (PASSIoN) in 10 neonates with PAIS showed that intranasal MSC administration was feasible and well tolerated, with no serious adverse events and promising early efficacy signals at 2-year follow-up. iSTOP-CP is a phase II, single-center (UMC Utrecht, the Netherlands), double-blind, randomized, placebo-controlled trial evaluating whether IN-MSC therapy can prevent or reduce motor and other disabilities in infants with MRI-confirmed HIBI due to PAIS or PA. Eligible infants are born at 35.0 weeks of gestation or later, have HIBI confirmed on brain MRI or MRS in predefined brain regions predictive of poor outcome, and are diagnosed with PAIS or PA, with or without prior therapeutic hypothermia. A total of 162 infants will be randomized 1:1 to IN-MSC or matching placebo, stratified by the cause of HIBI and, within the PAIS group, by stroke territory. Infants with suspected chromosomal, metabolic, or congenital central nervous system anomalies, intracranial hemorrhage as the main injury, or contraindications to intranasal administration are excluded, as are infants for whom the clinical team has decided to withdraw intensive care. Participants receive a single intranasal dose of bone marrow-derived MSC or a visually indistinguishable placebo within 7 days after birth. Participants are followed for 24 months, with neurodevelopmental follow-up visits at 3-4, 6, 9-12, and 24 months of age and a brain MRI at 52 weeks postmenstrual age. The primary endpoint is the motor composite score of the Dutch version of the Bayley Scales of Infant and Toddler Development, 4th edition (Bayley-IV-NL), assessed at 24 months corrected age. Key secondary endpoints include cognitive development, the incidence of sensorineural disability, neuroregenerative imaging biomarkers, safety, health-related quality of life for infants and their parents, and the cost-effectiveness of IN-MSC treatment, evaluated through a health technology assessment.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo | Administration fluid (=physiological saline (0.9% NaCl; RVG 051680) with 10% Human Serum Albumin (RVG 103594)) |
| MSC, marrow | Experimental | Drug: MSC, marrow | Bone-marrow derived mesenchymal stromal cells (BM-MSCs) intranasally administered once within 7 days after birth. |
Sex: All, ages: 0 Days to 8 Days
Inclusion Criteria: * Neonates with a gestational age ≥35.0 weeks at birth * Diagnosed with HIBI on MRI, caused either by PAIS (ORPHA 439175) or PA (ORPHA 137577) diagnosis (will be randomized separately) o PAIS: a neurologic condition characterized by focal cerebral ischemia and infarction following blockage of a brain artery with impairment of blood supply and oxygenation of brain tissue, clinically characterized by seizures (clinical or subclinical), respiratory difficulties, or both (unilateral or bilateral). o PA: defined as at least one out of the following: 5-min Apgar score ≤ 5 * Resuscitation * Mechanical ventilation following resuscitation ≥ 10 minutes after birth * pH <7.0, BE <-16 mmol/L, or lactate > 10.0 mmol/L in umbilical cord blood sample, or in arterial, venous or capillary blood gas sample obtained within 1 hour after birth * Showing signs of hypoxic-ischemic injury in one or more of the following predefined brain areas (indicated by DWI restriction and/or abnormal ADC values and/or 1H-MRS lactate/N-acetyl aspartate (NAA) and/or NAA/Choline ratio abnormalities): * Central gray matter (basal ganglia and/or thalami), and/or * Posterior limb of the internal capsule (PLIC), and/or * Cerebral peduncles, and/or * White matter injury with corticospinal tract (CST) involvement, and/or * Rolandic cortex * Written informed consent from custodial parent(s) Exclusion Criteria: * Suspicion of chromosomal anomaly, metabolic disorder, genetic syndrome, congenital central nervous system (CNS) malformation, congenital CNS infection and main injury intracranial haemorrhage. * Once a clinical team decides on withdrawal of Neonatal Intensive Care Unit (NICU) care, the patient is not eligible for inclusion: infants with very severe brain injury on MRI and need for ventilation support (not breathing independently), who have a prognosis of severe multiple handicaps and/or no realistic prospect of survival at the discretion of the infant's clinical care team in the NICU, will not be eligible for iSTOP-CP, to avoid unnecessary suffering and an unacceptable quality of life. * Contraindications for intranasal administration of medication, nasal obstruction caused by e.g. choanal atresia, nasal septal abnormalities, nasal trauma, epistaxis, excessive nasal mucus or blood, and intranasal obstructive damage.
NIH grants: 2025