Clinical Research Directory

Intranasal Stem Cells to Treat Perinatal Brain Injury to Combat Cerebral Palsy

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.

COMPARISON OF OUTCOME OF HYPOXIC ISCHEMIC ENCEPHLOPATHY MANAGED WITH COMBINATION OF MAGNESIUM SULPHATE AND MELATONIN VERSUS MAGNESIUM SULPHATE ALONE

COMPARISON OF OUTCOME OF HYPOXIC ISCHEMIC ENCEPHALOPATHY MANAGED WITH COMBINATION OF MAGNESIUM SULPHATE AND MELATONIN VERSUS MAGNESIUM SULPHATE ALONE Participants of group A will have 3 doses of MgSO4 infusion at rate of 250mg/kg per day intravenous over 1hour on day 0,1,2 Participants of group B will have 5 doses of Melatonin 10mg/kg for 5days along with MgSO4. They will undergo reassessment of arterial PH and serum LDH after completion of therapy. They will be followed for length of hospital stay and time until feed is initiated.

Assessing Intellectual and Motor Outcomes in High-risk Infants

Cerebral palsy (CP) is a condition when a baby has a brain injury that affects their movement and muscle tone. Some people with CP can have other developmental issues, like learning impairments, but many do not and have isolated issues with their motor skills. Some newborns are at higher risk of developing CP, including babies born prematurely, those who have an injury to their brain, and those who have an abnormal neurological examination. However, most babies with a higher risk of CP do not develop CP. The problem is that doctors can't tell early on who will and who will not develop CP, they can only say who has a risk of it. Therefore, these babies are followed up in out-patient clinics to see how they are progressing, usually by a neonatologist (baby doctor), often a physiotherapist, and some may also be referred to services in the community like the Early Intervention Team. If there is a significant concern, doctors will often perform a scan of the baby's brain to provide more information. Even with all this follow-up, it still usually takes at least 12 months, and can be up to 2 years, to diagnose a child as having CP. In this study the aim is to try and reduce the age of diagnosis of CP by assessing children in high-risk out-patient clinics using novel and specific examinations. We would also like to improve our ability to predict who will need help with learning, language or other non-motor outcomes. This study is being conducted at several hospitals in Ireland, including Cork University Maternity Hospital (CUMH), The Rotunda Hospital and the Coombe Women and Infants Hospital. It is being coordinated by the In4kids network and will be conducted in the INFANT Centre/ University College Cork (UCC). The study has been funded by Research Ireland and the Cerebral Palsy Foundation, USA.

Biomarkers Study in Infants With Prior Neonatal Brain Injury

This research focuses on the long-term cognitive development of children, including healthy infants and those who had a perinatal brain injury. As part of this research study, children complete in-person games and assessments at UW-Madison University Hospital. Children will also take part in an EEG assessment. Parents will be asked to fill out questionnaires about their child's behavior and stress in the home.

Treatment of Seizures in Neonate With HIE

Aim of the study To evaluate and compare phenobarbital's and levetiracetam's safety and efficacy for treating seizures in neonates with moderate to severe HIE

Speech of Kids After Neonatal Encephalopathy

The goal of this ambispective cohort study is to reveal the early indicators of delayed language development in children born with hypoxic-ischemic encephalopathy (HIE). We will examine the prognostic accuracy of different biomarkers, with a special focus on the ADC values of the corpus callosum. The main questions it aims to answer are: 1. To what extent does hypoxic-ischemic encephalopathy (HIE) in infancy affect intellectual development (IQ), receptive and expressive language abilities at different levels of the language system, and memory capacities related to language development? 2. What is the relationship between early biomarkers of brain injury-such as blood gas levels, lactate, aEEG, and MRI findings (Weeke scoring system, ADC values of the corpus callosum)-and long-term cognitive developmental outcomes? 3. What is the incidence of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in this high-risk population of infants with HIE? 4. Is there an association between the Weeke Total Score and long-term language developmental outcomes? 5. Can restricted diffusion (ADC values) of the splenium of the corpus callosum serve as an early neuroradiological marker of developmental language disorder (DLD)? Our participants are children born between 2017 and 2023 with moderate to severe HIE, treated with therapeutic hypothermia at Semmelwies University Children's Hospital. During their first days of life, several neonatal measurements were taken (blood gas markers, aEEG etc.), and at day 4-5, they had an MRI scan of their brain. The MRI scans will be reanalyzed, using the Weeke MRI scoring system. These children underwent a neurodevelopmental follow-up at the age of 2 years and currently, they will have another follow-up at the age of 4-7 years.