Clinical Research Directory

Dose Optimization of Caffeine for HIE

This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.

Sildenafil Plus Hypothermia to Treat Neonatal Encephalopathy

The main objective of this study is to assess pharmacokinetics features of IV sildenafil in neonates with hypoxic-ischemic encephalopathy and treated by controlled hypothermia. This phase 2 study will prepare a large phase 3 randomized controlled trial to demonstrate the superiority of a combinatory therapy associating IV sildenafil and controlled hypothermia compared to Placebo and controlled hypothermia, on survival without brain lesions on MRI at discharge, in neonates born after 36 weeks of gestation.

A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury

Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE.

Hydrogen In Neonatal Encephalopathy (HIE) Trial

Despite advances in neonatal care, moderate-to-severe acute perinatal HIE in late preterm and term infants remains a cause of mortality, neurological injury, and long-term neurodevelopmental disability. The current standard of care includes therapeutic hypothermia for 72 hours, but 40-50% of infants will die or suffer significant neurodevelopmental impairment. It has been shown that administration of hydrogen gas (H2) significantly diminishes ischemic injury in swine, and that H2 administration at the dose and duration proposed herein is well-tolerated in healthy adults. The purpose of this project is to test the feasibility and safety of H2 administration as an adjunct to therapeutic hypothermia in infants with HIE. Under exemption from informed consent, infants with severe, acute brain injury at birth will be randomized to standard therapy with or without the administration of 2% hydrogen in gases administered via the ventilator, non-invasive ventilation, or nasal cannula for 72 hours.

Comparative Outcomes Related to Delivery-room Cord Milking In Low-resourced Kountries

The investigators will conduct a study on non-vigorous infants at birth to determine if umbilical cord milking (UCM) results in lower rate of moderate to severe hypoxic ischemic encephalopathy (HIE) or death than early clamping and for infants who are non-vigorous at birth and need immediate resuscitation.

Florida Neonatal Neurologic Network

Create a database with selected medical information on infants born with hypoxic-ischemic encephalopathy (HIE). In addition, the following samples will be collected in a bio-repository for future studies: blood, urine, and buccal samples.

Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy

The NSR-GENE study is a longitudinal cohort study of approximately 300 parent-child trios from the Neonatal Seizure Registry and participating site outpatient clinics that aims to evaluate whether and how genes alter the risk of post-neonatal epilepsy among children with acute provoked neonatal seizures. The researchers aim to develop prediction rules to stratify neonates into low, medium, and high risk for post-neonatal epilepsy based on clinical, electroencephalogram (EEG), magnetic resonance imaging (MRI), and genetic risk factors.

Assess Safety and Efficacy of Sovateltide in Hypoxic-ischemic Encephalopathy

Sovateltide (PMZ-1620; IRL-1620) is targeted to be used as a "Treatment for hypoxic-ischemic encephalopathy in neonates," which is a life-threatening condition. Sovateltide augments neuronal progenitor cell differentiation and better mitochondrial morphology and biogenesis to activate a regenerative response in the central nervous system. The only treatment for HIE is therapeutic hypothermia with limited success, and studies indicate that sovateltide may be beneficial in these patients.

A Study of a Blood Marker in Newborns With Brain Injury Caused by Lack of Oxygen at Birth

Perinatal asphyxia is a significant health problem with an incidence of 1 to 8 per 1,000 live births and can lead to serious morbidity and mortality during the neonatal period. One of its most severe consequences is hypoxic-ischemic encephalopathy (HIE), a condition that causes irreversible damage to the newborn brain due to hypoxia and ischemia. HIE is one of the leading causes of long-term neurological sequelae. Therapeutic hypothermia initiated within the first six hours after birth has been shown to significantly reduce both mortality and neurodevelopmental impairments associated with HIE. However, biomarkers that can reliably predict individual treatment response or objectively demonstrate the severity of brain injury at an early stage remain limited. Neurofilament light chain (NfL) is a protein found within the cytoskeletal structure of myelinated axons. When axonal injury occurs, NfL is released into the interstitial space and subsequently enters the cerebrospinal fluid and systemic circulation, where it can be measured. Increased NfL levels have been identified in a variety of neurological conditions, including neurodegenerative disorders and traumatic brain injury. Recent findings show that both cerebrospinal fluid and serum/plasma NfL levels are elevated in newborns diagnosed with HIE, supporting its potential role as a biochemical marker of axonal injury. The primary aim of this study is to investigate the time-dependent changes in serum NfL levels in newborns diagnosed with HIE and undergoing therapeutic hypothermia, and to evaluate the relationship between these changes, clinical findings, and neuroimaging results. For this purpose, serum NfL levels were measured at four specific time points: within the first six hours after birth (preferably cord blood), upon reaching the target cooling temperature (approximately 12-24 hours), during the rewarming phase (72-96 hours), and on the day of magnetic resonance imaging (preferably day seven). The results are expected to provide insights into the prognostic utility of NfL in HIE and contribute to determining the optimal timing for clinical sampling. The secondary objective of the study is to compare NfL levels of newborns diagnosed with HIE to those of a control group without HIE, thereby identifying potential cut-off values that may help distinguish between affected and unaffected infants.

A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures

The main purpose of this study is to determine the maximum safe tolerated dose of LEV in the treatment of neonatal seizures. Our hypothesis is that optimal dosing of Levetiracetam (LEV) to treat neonatal seizures is significantly greater than 60mg/kg. This study will be an open label dose-escalation, preliminary safety and efficacy study. There will be a randomized control treatment component. Infants recognized as having neonatal seizures or as being at risk of developing seizures will be recruited and started on continuous video EEG monitoring (CEEG). Eligibility will be confirmed and consent will be obtained. In the first 2 phases of the study, neurologists will identify neonates with mild-moderate seizure burden (less than 8 minutes cumulative seizure activity per hour), appropriate for study with LEV, and exclude patients with higher seizure burden where treatment with PHB is more appropriate. Phase 3 of the dose escalation will only proceed if additional efficacy of LEV has been demonstrated in phases 1 and 2. In Phase 3 we will recruit neonates with seizures of greater severity up to 30 minute seizure burden/hour. This will make the final results of study more generalizable. If seizures are confirmed, enrolled subjects will receive 60mg/kg of LEV. Subjects whose seizures persist or recur 15 minutes after the first infusion is complete, subjects will then be randomized in the dose escalation study. Patients in the dose escalation study will be randomly assigned to receive either higher dose LEV or treatment with the control drug PHB in a 3:1 allocation ratio, stratified by site. Funding Source- FDA OOPD

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of RLS-0071 in Newborns With Moderate or Severe Hypoxic-Ischemic Encephalopathy Undergoing Therapeutic Hypothermia

Hypoxic-ischemic encephalopathy (HIE) affects approximately 4,000 to 12,000 persons annually in the United States. Mortality from HIE has been reported up to 60%, with at least 25% of survivors left with significant neurocognitive disability. Despite this vital unmet medical need, no pharmacological adjunct or alternative therapy has proven beneficial in improving outcomes in neonatal HIE. RLS-0071 is a novel peptide being developed for the treatment of neonatal HIE. This study is designed to evaluate the safety and tolerability of RLS-0071 in the treatment of newborns with moderate or severe HIE.

Prognostic Factors to Regain Consciousness

The study aims to identify factors that predict the medium and long-term outcome of patients with disorders of consciousness (DOC) undergoing early neurological rehabilitation. In this prospective, observational study, 130 DOC patients are going to be included (36 months). At study entry, different routine data, disease severity and functional status are documented for each patient. In addition, MRI, EEG and evoked potentials are measured within the first week. The level of consciousness is recorded with the Coma-Recovery-Scale-Revised and serves as the primary outcome parameter. Complications, comorbidities, functional status and leve of consciousness are assessed weekly. After eight weeks, the measurement of the MRI, the EEG and the evoked potentials are repeated. After 3, 6 and 12 months, the Glasgow Outcome Scale-Revised is used to followed up the current status of the patients.

Spinal Stimulation and Mobility Devices

This research study will combine non-invasive spinal stimulation with mobility devices to examine the acute impact of the individual and combined effects of these innovative techniques on mobility in children with cerebral palsy.

Nephroprotection Following Perinatal Asphyxia: Randomized Controlled Trial

The aim of this study is to determine the value of Pentoxifylline for nephroprotection in these neonates with perinatal asphyxia, using cystatin C, regional oxygenation measured near infrared spectroscopy and renal Doppler sonography.

Comparative Outcomes Related to Delivery-room Cord Milking In Low-resourced Kountries Developmental Follow Up

An extension of the CORDMILK trial, the CORDMILK follow-up trial will evaluate the neurodevelopmental outcomes at 22-26 months age of term/late preterm infants who were non-vigorous at birth and received umbilical cord milking (UCM) or early cord clamping (ECC).

Predicting Mortality in Patients With Return of Spontaneous Circulation After Cardiac Arrest

This observational study aims to identify early predictors of in-hospital mortality in adult patients who achieved return of spontaneous circulation (ROSC) after cardiac arrest. The study prospectively enrolls patients admitted to the intensive care unit at a tertiary care hospital in Turkey. Various clinical, biochemical, and resuscitation-related parameters will be recorded within the first 24 hours of ICU admission. The primary goal is to determine which factors are most strongly associated with mortality within 30 days. The findings are expected to improve clinical decision-making and risk stratification in the management of post-cardiac arrest patients.

Effects of a Physical Therapy Intervention on Motor Delay in Infants Admitted to a Neonatal Intensive Care Unit

Study Aims Pilot study: Due to the large recruitment goal and length of the project, the study team/PIs will evaluate the first cohort of 6-10 participants to refine study procedures and study-related materials. If no major modifications are made to the protocol as a result of this evaluation, data from these participants will be included for analysis. Aim 1: Evaluate the efficacy of an early, evidence-based, clinical experience-based therapeutic intervention (from the NICU to 12-months corrected age) on improving motor function and reducing severity of motor delays in infants at 12-months corrected age. The investigators hypothesize that the intervention group will demonstrate an average 8-point difference (0.5 standard deviation) compared to the standard of care group. \[an 8-point difference is considered a clinically meaningful difference\] Aim 2: Evaluate the early effects (i.e., before 12 months) of a therapeutic intervention, provided from NICU to 12-months corrected age, on motor function and severity of motor delay. The Investigators hypothesize that a statistically significant higher percentage of infants in the intervention group will demonstrate improved motor function and reduced severity of motor delays, compared to the standard of care group-assessed using sensors, the NSMDA and TIMP-as early as 3-months corrected age. Aim 3: Evaluate whether an early intervention that focuses on caregiver engagement improves caregiver well-being. The invetigators hypothesize that an intervention that focuses on supporting and addressing the individual needs of the caregiver will improve caregiver well-being. The investigators will evaluate these effects using the PedsQL (Family Impact Module).

Healthy Little Eyes

The purpose of this research study is to gather more information on how eye injury is related to a baby's future development and see if eye function and brain test results can be used, along with current measures, to better diagnose and treat babies with hypoxic-ischemic encephalopathy (HIE). Participants will undergo up to two eye exam sessions, involving both Visual Evoked Potential (VEP) and Electroretinogram (ERG) exams.

Neuromotor Development and Motor Related Health Care in Children with a High Risk Neonatal Period

The overall aim of the study is to evaluate the prevalence of motor- and neurological disorders (cerebral pares and other less severe motor disorders) in Swedish infants with a high-risk neonatal period and to elucidate whether these children receive motor related health care (MRHC) at 2 and or 5,5 years of age.

Efficacy Evaluation of UCB-MNCs in the Treatment of Refractory Neonatal Diseases

Hypoxic-ischemic encephalopathy (HIE), bronchopulmonary dysplasia (BPD), short bowel syndrome (SBS) are refractory in clinical treatment. Thus, how to better prevent such diseases is currently a key research topic in the international field. The use of cord blood-derived mononuclear cells may promote to save lives and improve patient outcomes.

Systemic Biomarkers of Brain Injury From Hyperammonemia

Ammonia is a waste product of protein and amino acid catabolism and is also a potent neurotoxin. High blood ammonia levels on the brain can manifest as cytotoxic brain edema and vascular compromise leading to intellectual and developmental disabilities. The following aims are proposed: Aim 1 of this study will be to determine the chronology of biomarkers of brain injury in response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic disorder. Aim 2 will be to determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn errors of metabolism, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1).

Hydrocortisone Therapy Optimization During Hypothermia Treatment in Asphyxiated Neonates

This is a prospective, single center, pharmacokinetic study of intravenous hydrocortisone therapy for systemic low blood pressure during hypothermia treatment in asphyxiated newborns. Patients will be allocated to hydrocortisone supplementation while receiving conventional inotropic therapy as needed. The hypothesis is that a detailed study of hydrocortisone pharmacokinetics during therapeutic hypothermia would help to personalize steroid supplementation in asphyxiated neonates. As the overall metabolic rate decreases with lower body temperature, drug metabolism is likely to be reduced as well, and lower doses, or less frequent dosing will be sufficient to achieve the targeted steroid range and biological effects in asphyxiated neonates with relative adrenal insufficiency. Thus, the investigators are planning to measure initial, baseline serum cortisol levels and serial serum cortisol levels after hydrocortisone supplementation in cooled asphyxiated neonates.

Early Virtual Intervention for Infants With CP Following HIE Diagnosis

This will be a five year study that will be a prospective, randomized, controlled trial (RCT) to assess the effect of a virtual early intervention care delivery model in the provision of therapy to enhance the neurodevelopmental trajectory of infants with brain injury. In addition, the investigators will enhance understanding of the social and parental contributors to outcomes and the early health economic impact of a virtual clinic. The results of this study will help inform the design of a larger, multi-center randomized controlled trial.