61 Clinical Trials for Various Conditions
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.
A phase 1 study investigating the tolerability and pharmacokinetics of caffeine citrate in neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia. This study is an essential first step to develop caffeine as a kidney protective medication in this in this vulnerable group of newborns.
The purpose of this study is to evaluate the feasibility and begin to evaluate the effect of a sensorimotor intervention (SMI) provided in the first 6 months of life for infants with hypoxic-ischemic encephalopathy.
This study aims to determine the safety of HB-adMSC infusion and treatment effects of HB-adMSC infusion on brain structure, neurocognitive/functional outcomes, and neuroinflammation after subacute and chronic neurological injury in adults.
Hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia is common and often fatal. Therapeutic hypothermia reduces mortality and morbidity in infants with HIE. Even with the widespread use of therapeutic hypothermia, \~60% of infants with HIE die or have neurodevelopmental impairment. As a result, there is an urgent, unmet public health need to develop adjuvant therapies to improve survival and neurodevelopmental outcomes in this population. Caffeine may offer neuroprotection for infants with HIE by blocking adenosine receptors in the brain and reducing neuronal cell death. In animal models of HIE, caffeine reduces white matter brain injury. Drugs in the same class as caffeine (i.e., methylxanthines) have been shown to be protective against acute kidney injury in the setting of HIE. However, their safety and efficacy have not been studied in the setting of therapeutic hypothermia and their effect on neurological outcomes is not known. Since these drugs reduce injury to the kidney in infants with HIE, they may also reduce injury to the brain. This phase I study will evaluate the pharmacokinetics, safety, and preliminary effectiveness of caffeine as an adjuvant therapy to improve neurodevelopmental outcomes in infants with HIE.
A longitudinal study evaluating the predictive ability of near infrared spectroscopy to predict brain injury in infants with hypoxic ischemic encephalopathy. Data will be analyzed at two different time periods, at discharge and again at 2 years of age.
The purpose of this study is to develop a novel noninvasive bedside optical coherence tomography (OCT) imaging technique in newborn infants with HIE that improves our ability to assess the range of retinal effects from HIE and to diagnose and monitor treatments of HIE.
Controlled Hypothermia has become the standard of care for neonates with moderate to severe HIE. Ampicillin and aminoglycosides are drugs that are universally used for the treatment of suspected neonatal sepsis, which may or may not be responsible for the etiology of HIE. Currently, medication dosage regimens are not altered in the setting of CH. A better understanding of the effects of our interventions on this unique population may help us tailor our therapy to the specific circumstances of the patient
This study will test the safety and efficacy of an infusion of a baby's own (autologous) umbilical cord blood as compared with placebo in babies born with history and signs of hypoxic-ischemic brain injury.
The purpose of this study is to investigate the safety and effectiveness of autologous human placental-derived stem cells (HPDSC) in combination with autologous cord blood in neonates with severe hypoxic-ischemic encephalopathy.
Hypoxic-ischemic encephalopathy (HIE) is a serious birth complication due to systemic asphyxia which occurs in about 20 of 1,000 full-term infants and nearly 60% of premature newborns. Between 10-60% of babies who exhibit HIE die during the newborn period and up to 25% of the HIE survivors have permanent neurodevelopmental handicaps in the form of cerebral palsy, mental retardation, learning disabilities, or epilepsy. HIE also has a significant financial impact on the health care system. In the state of Florida, the total cost for initial hospitalization is $161,000 per HIE patient admitted, but those costs don't take into account the life-long costs. Current monitoring and evaluation of HIE, outcome prediction, and efficacy of hypothermia treatment rely on a combination of a neurological exam, ultrasound, magnetic resonance imaging (MRI) and electroencephalography (EEG). However, these methods do a poor job in identifying non-responders to hypothermia. MRI requires transport of the neonate with a requisite 40-45 min scan, which is not appropriate for unstable neonates. Moreover, the amplitude integrated EEG (aEEG), a common bedside monitoring technique currently used in these patients to assess candidates and predict outcomes prior to hypothermia, can be adversely affected by hypothermia itself and the patient may not appear to improve until re-warming. Consequently, the development of a simple, inexpensive, non-invasive, rapid biochemical test is essential to identify candidates for therapeutic hypothermia, to distinguish responders from non-responders and to assess outcome. This research is the first step needed to treat neonates with HIE employing a personalized medical approach using serum proteins GFAP and UCH-L1 as biomarkers and by monitoring neonates responses to therapeutic hypothermia. These biomarkers will aid in the direct care by providing a rapid test to predict outcomes and select candidates who are likely to benefit from therapeutic hypothermia and gauge a response to the neuroprotective intervention.
During the birth process certain conditions can cause oxygen delivery and/or blood flow to the baby's brain to become interrupted. This can cause permanent brain damage. Brain damage occurs in two phases. The first occurs at the time of injury when brain cells in the affected area 'die'. There is nothing that can be done about this. The second phase of injury occurs over the next few days. This second phase is caused by inflammation and release of toxic chemicals from the injured site. Cooling the baby to a temperature of 92.5° F, for 3 days has been shown to reduce the second phase of injury and bran death. All babies will receive the benefit of cooling. Although cooling helps it does not completely stop the second phase of injury. Melatonin is a naturally occurring hormone that is produced by the brain, and helps regulate the sleep-wake cycle. It has the potential to stop the second phase of brain injury by inhibiting inflammation and release of toxic chemicals. The reason for this research is to find out if melatonin can or cannot improve the outcome of babies with this kind of brain damage. Every baby enrolled in the study has a 50:50 chance of getting melatonin. A total of six doses of medicine will be given. The baby's brain function will be assessed by an EEG, brain oxygen monitoring, and a neurologic examination at 18 months of life. All of these are routinely used as part of standard care for patients with this kind of problem. The only difference is that half the babies enrolled in the study will get the drug called melatonin and the other half will receive placebo. The dose of melatonin being used in the study is higher than the amount normally produced by the body. No side-effects of this dose have been reported in other research studies using melatonin in newborn and premature babies.
This research is being done to find out the safety of the investigational study drug, Clonidine Hydrochloride ( CLON). , in infants who are undergoing whole body cooling for the treatment of hypoxic ischemic encephalopathy (HIE). The only known and effective treatment for HIE is therapeutic hypothermia or whole body cooling for72 hours. During the cooling process, babies get agitated, shiver and are uncomfortable. To treat these side effects morphine is frequently used. CLON is very effective in decreasing shivering in adults and children. Furthermore, in some preclinical studies, clonidine has been shown to be neuroprotective (safe for the brain in models of brain injury)..This is a Phase I-II to determine if low dose CLON will reduce the incidence of shivering and whether it has short term cardiovascular safety. In this Phase I-II study, the investigators will determine the (i) the maximum tolerated dose of CLON during cooling for HIE, (ii) the effects of CLON on heart rate, blood pressure, core body temperature and cerebral autoregulation (ability to maintain constant blood flow to the brain) and (iii) association between blood levels and changes in the above parameters. In this study the investigators hope to find ways to improve sedation, shivering and agitation in newborn infants with HIE on the cooling protocol. Our ultimate goal is determine the potential neuro-protective properties of clonidine in newborn babies with HIE.
The goal is to see whether topiramate (an anti-epileptic agent) improves the outcome of babies with neonatal hypoxic encephalopathy who are receiving whole body cooling.
The Optimizing Cooling trial will compare four whole-body cooling treatments for infants born at 36 weeks gestational age or later with hypoxic-ischemic encephalopathy: (1) cooling for 72 hours to 33.5°C; (2) cooling for 120 hours to 33.5°C; (3) cooling for 72 hours to 32.0°C; and (4) cooling for 120 hours to 32.0°C. The objective of this study is to evaluate whether whole-body cooling initiated at less than 6 hours of age and continued for 120 hours and/or a depth at 32.0°C in will reduce death and disability at 18-22 months corrected age.
Hundreds of babies in the world are being treated with brain cooling to prevent brain injury after they lose oxygen at birth. This study will use the newly developed information from the magnet resonance image to determine the actual temperature of the brain. This will enable us to determine if the brain is being uniformly cooled and if techniques that provide cooling need to be changed to improve the injury prevention from cooling.
The hypothesis is that premature infants' can have enough cooling applied to cool their brain to decrease CNS injury without cooling their body.
This study is a randomized, placebo-controlled, clinical trial to evaluate whether induced whole-body hypothermia initiated between 6-24 hours of age and continued for 96 hours in infants ≥ 36 weeks gestational age with hypoxic-ischemic encephalopathy will reduce the incidence of death or disability at 18-22 months of age. The study will enroll 168 infants with signs of hypoxic-ischemic encephalopathy at 16 NICHD Neonatal Research Network sites, and randomly assign them to either receive hypothermia or participate in a non-cooled control group.
This is a pilot study to test feasibility of collection, preparation and infusion of a baby's own (autologous)umbilical cord blood in the first 14 days after birth if the baby is born with signs of brain injury.
This is a research study of head cooling. Its goal is to determine whether cooling babies' heads can reduce or prevent brain damage that may have resulted from temporarily reduced oxygen supply to the brain. In this study, half of the babies (selected at random) will have a special cooling cap with circulating water placed on their head for 72 hours to lower the temperature of their brain. The rest of the baby's body will be maintained at a defined temperature by a standard overhead radiant heater. The study protocol includes the taking and analysis of blood samples, performance of brain wave tests, imaging of the brain by ultrasound, and other tests as clinically indicated. Neurodevelopmental outcome will also be assessed at 18 months of age.
Perinatal hypoxic-ischemic encephalopathy is a rare severe condition in which neonates present with encephalopathy and a clinical history suggestive of prenatal or perinatal hypoxic-ischemic injury. Emerging evidence suggests that genetic conditions are frequently identified in cases of perinatal HIE; however, it is unclear which neonates with this diagnosis warrant genetic testing. This study will offer clinical genome sequencing to neonates with HIE who are undergoing total body cooling (therapeutic hypothermia) and their parents.
The goal of this behavioral-interventional study is to learn if the Abecedarian Approach implemented virtually for children ages 0-5 with a history of Hypoxic Ischaemic Encephalopathy (HIE) and/or premature birth produces the same effects as when administered at in-person facilities.
This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.
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.
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.
The purpose of the research is to determine if the Hepatitis B vaccine after birth provides enough protection after cooling for Hypoxic Ischemic Encephalopathy (HIE). To do this, Hepatitis B titers (blood sample) would be taken before, during, and after administering of the Hepatitis B vaccine series to measure efficacy of the vaccine.
Management of neonatal pain and sedation often includes opioid therapy. A growing body of evidence suggests long-term harm associated with neonatal opioid exposure. Providing optimal sedation while neonates are undergoing therapeutic hypothermia (TH) may be beneficial but also presents therapeutic challenges. While there is evidence from animal models of brain injury and clinical trials in adults to support the safety and neuroprotective properties of dexmedetomidine (DMT), there are no published large clinical trials demonstrating safety and efficacy of DMT use in neonates with hypoxic-ischemic encephalopathy (HIE) during treatment with TH. This study is innovative in proposing a Phase II, 2-arm trial providing the opportunity to evaluate the use of DMT as compared to the use of morphine for sedation and pain management for babies undergoing TH. We propose to confirm optimal DMT dosing by collecting opportunistic pharmacokinetics (PK) data and determine safety of DMT in this population. These data will inform a larger phase III efficacy trial.
To determine effectiveness of therapy to improve neurodevelopmental outcomes in infants with mild HIE. To determine the adverse effects of Therapeutic Hypothermia (TH) in mild HIE on the neonate and his/her family. Determine heterogeneity of the treatment effect across key subgroups obtained in the first 6 hours after birth prior to the decision to initiate therapy.
The TIME study is a randomized, controlled trial to evaluate impact on early measures of neurodevelopment and the safety profile of therapeutic hypothermia in term neonates with Mild Hypoxic-Ischemic Encephalopathy who are \< 6 hours of age. Neurodevelopmental outcome will be assessed at 12-14 months of age. The study will enroll 68 neonates randomized to therapeutic hypothermia or normothermia across 5 centers in California.
This research is being done to try to improve the experience of mothers and babies during therapeutic hypothermia. Currently, mothers are not able to hold their baby during hypothermia treatment. Mothers have reported that not being able to hold their baby during this time is stressful. Additionally, it is known that holding has many benefits for mothers' and babies' psychological and physical health. Therapeutic hypothermia is the standard of care. The experimental interventions of this study are to have mothers hold their babies during this treatment, collect saliva samples from mothers and babies, and test the saliva samples for the hormones cortisol and oxytocin. The investigators will test saliva of infants and their mothers before and after holding. The investigators hope to demonstrate decreased cortisol, a marker for stress, and increased oxytocin, a marker for bonding, in infants and mothers while they are held during therapeutic hypothermia.