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: 0
• Participant gender: All

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.

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

Details

• Lead Sponsor: The Hospital for Sick Children
• Collaborators: University of Alberta; University of Waterloo
• Treatments: Metformin

Criteria

Inclusion Criteria:

1. > 35 weeks gestation at time of birth

2. ≤3 months at time of consent

3. Clinical diagnosis of HIE

4. Infant received therapeutic hypothermia for the treatment of HIE#

5. Family lives within one hour distance of the Hospital for Sick Children (in order to facilitate home visits)

Exclusion Criteria:

1. Have a known genetic or chromosomal disorder.

2. Congenital or acquired liver or kidney disease that might, in the opinion of the Principal Investigator or delegate, affect drug metabolism.

3. History of hypoglycemia in the newborn period requiring glucose infusion rate > 10 mg/kg/min or treatment with glucagon or diazoxide.

4. Any condition or diagnosis, that could in the opinion of the Principal Investigator or delegate, interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk

5. >3 months of age at the time of enrollment

6. Weight <10%ile based on WHO growth charts at time of initiation of study drug.