NVD in Hypothermic HIE Neonates

• Status: Completed
• Trial end date: 2020-03-01
• Target enrollment: 0
• Participant gender: All

Summary

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
• Accepts Healthy Volunteers?: No

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)
• Treatments: Acetylcysteine; Calcitriol; N-monoacetylcystine

Criteria

Inclusion Criteria:

• Neonates > 34 weeks, > 2000 grams, within 6h of birth with moderate to severe HIE receiving therapeutic hypothermia

Exclusion Criteria:

• Evidence of a congenital CNS malformation if known prior to enrollment

• Evidence of neuromuscular disorder by family history

• More than 6 hours from birth or known insult

• Suspected genetic abnormality