A Phase I Safety and Feasibility of Metformin Treatment in Infants After Perinatal Brain Injury
Status:
Not yet recruiting
Trial end date:
2024-12-31
Target enrollment:
Participant gender:
Summary
In recent years, the drug metformin has emerged as a promising neuroprotective agent, with
numerous in vitro and in vivo studies demonstrating positive impact on the birth of new
neurons (neurogenesis) and the ability of the brain to adapt after injury (neuroplasticity).
Importantly, in preclinical and clinical studies in older children, metformin can be
administered months after the initial brain injury, as the mechanism of action improves
neural circuit remodeling and recovery. This is important, as metformin can potentially serve
as a neuro-restorative agent after the initial insult during the newborn period. Metformin
has been used as an anti-hyperglycemic drug for over 60 years with very limited safety
concerns. However, metformin has not been administered to children under 2 years, nor has it
been administered to infants after brain injury. Given the unique drug metabolism of infants,
it is critical to establish the safety, maximum tolerated dose, and drug metabolism of
metformin in this population before proceeding to studies of metformin efficacy for
HIE-associated brain injury. Therefore, we propose a Phase I randomized safety and
feasibility trial of metformin in infants affected by HIE, to assess the safety and
feasibility of metformin administration in infants, and to measure the pharmacokinetics and
pharmacodynamics of metformin in infants with HIE.