Enrolling by invitation NCT06429007
A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Metformin.
- Who it may be relevant to
- Registry conditions: Hypoxic-Ischemic Encephalopathy, HIE, Neurodevelopment, Infant Development. Basic parameters: 3 months — 6 months · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE.
Interventions
- Drug Metformin
Metformin will be initiated at 25% of the target dose (4 mg/kg administered twice daily, total daily dose 8 mg/kg) for three weeks. In the absence of adverse effects, metformin dose will be escalated to 50% of the target dose (8 mg/kg administered twice daily for a total daily dose of 16mg/kg) for remaining 3 weeks to minimize potential gastrointestinal upset at higher doses. Parents will be documenting adverse events and performing glucometer checks twice a day for 3 days post dose escalation.
Primary outcome measures
- Safety profile of kidney function [Time frame: 12 weeks]
- Safety profile of liver function [Time frame: 12 weeks]
- Recruitment feasibility [Time frame: 12 weeks]
Secondary outcome measures (1)
- Validity of neonatal model of metformin pharmacokinetics [Time frame: 12 weeks]
Eligibility criteria
Inclusion criteria
- <6 months old at time of enrollment, and able to initiate study drug between 3 and 6 months old.
- Born > 35 weeks gestational age with a clinical diagnosis of HIE at birth, who receive therapeutic hypothermia.
- Post-hypothermia brain MRI with evidence of hypoxic-ischemic brain injury, based on the neuroradiology clinical report. Specifically, participants must have had evidence of a lactate peak by magnetic resonance spectroscopy and/or signal abnormalities by conventional (T1 and/or T2) or diffusion-weighted images consistent with hypoxic-ischemic pattern of injury.
- English- or Spanish-speaking families, as the parents/guardians will be responsible for documenting dose administrations and adverse events.
Exclusion criteria
- Known genetic or chromosomal disorder, and in the presence of congenital or acquired liver or kidney disease that might, in the opinion of the Principal Investigator (PI) or delegate, affect drug metabolism.
- Maternal use of metformin while actively breastfeeding.
- Infant weight below the 10th percentile based on WHO growth charts at the time of study drug initiation.
- Normal post-hypothermia brain MRI, without evidence of ischemic brain injury, based on the neuroradiology clinical report.
- Concomitant use of the following drugs: anti-diabetic drugs (insulin, sulfonylureas), steroids, diuretics (furosemide, chlorothiazide, spironolactone), diazoxide, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers (including nifedipine), phenytoin, valproic acid, topiramate, cimetidine, corticosteroids, thyroid medications, sympathomimetics, carbonic anhydrase inhibitors, or any antibiotics.
- Any condition or diagnosis, that could in the opinion of the PI 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Boston Children's Hospital — Boston
Publications
- Hutchinson AM, Pais R, Endginton AN, Pilon B, MacDonald JM, MacDonald ME, Lewis T, Offringa M, Kalish BT. Safety and feasibility trial protocol of metformin in infants after perinatal brain injury. BMJ Paediatr Open. 2025 Aug 24;9(1):e002784. doi: 10.1136/bmjpo-2024-002784. PMID 40850908
Identifiers
NCT: NCT06429007 · IRB-P00048370