Caffeine for Hypoxic-Ischemic Encephalopathy

• Status: Recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Thrasher Research Fund
• Treatments: Caffeine; Caffeine citrate; Citric Acid; Sodium Citrate

Criteria

Inclusion Criteria:

• Documented informed consent from parent or guardian

• ≥ 36 weeks gestational age at birth

• Receiving therapeutic hypothermia for a diagnosis of HIE

• Intravenous (IV) access

• Postnatal age < 24 hours

Exclusion Criteria:

• Receiving > 1 anti-epileptic drug for seizures

• Sustained (>4 hours) heart rate > 180 beats per minute

• Known major congenital anomaly

• Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study