Neonatal hypoxic ischemic (HI) injury is an unpredictable neurologic injury with devastating,
long term consequences for parents who are expecting a normal child. Hypothermia for 72 hr
within 6 hrs of birth improves the combined outcome of death or severe disability, and
hypothermia is now standard of care in tertiary centers throughout the world. However,
approximately 50% of infants with hypoxic ischemic encephalopathy (HIE) treated with
hypothermia still have adverse neurologic outcomes, due to ongoing neuroinflammation and
oxidative stress in spite of hypothermia. Further, the majority of HIE infants are
insufficient or deficient in a critical neurosteroid, 25(OH)vitamin D, which has been shown
to adversely affect outcome after adult stroke. By adding vitamin D to N-acetylcysteine
(NAC), an antioxidant, the investigators hypothesized that both drugs would increase
glutathione (GSH) concentrations in critical brain areas, mitigate continuing oxidative
stress after injury during hypothermia and after rewarming, and improve neurodevelopmental
outcomes.
This is an open-label, non-randomized, escalating dose, pilot trial to evaluate the
disposition and safety of NAC in combination with active vitamin D in neonates who present
within 6 hrs of hypoxia ischemia/asphyxial event and received moderate hypothermia to 33
degrees C for 72 hours per routine protocol.
Phase:
Early Phase 1
Details
Lead Sponsor:
Medical University of South Carolina
Collaborators:
Carlos III Health Institute National Institute for Health Research, United Kingdom National Institute of Neurological Disorders and Stroke (NINDS)