Metformin Treatment in Infants After Perinatal Brain Injury

Study Overview
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Brief Summary
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A phase I study to test the feasibility and safety of treatment with metformin in infants affected by hypoxic ischemic encephalopathy (HIE) or prematurity-related brain injury

Official Title
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A Phase I Safety and Feasibility of Metformin Treatment in Infants After Perinatal Brain Injury

Conditions
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Hypoxic Ischemic Encephalopathy of Newborn, Premature Birth

Intervention / Treatment
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* Drug: Metformin Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIE Patients: > 35 weeks gestation at time of birth ≤3 months at time of consent Clinical diagnosis of HIE Infant received therapeutic hypothermia for the treatment of HIE Family lives within one hour distance of the Hospital for Sick Children (in order to facilitate home visits) Preterm Infants: <32 weeks gestation at time of birth 36-44 weeks corrected (postmenstrual) gestational age at time of metformin administration Clinical team anticipates hospitalization at SickKids for at least 1 week after study enrollment Exclusion Criteria: Have a known genetic or chromosomal disorder. Congenital or acquired liver or kidney disease that might, in the opinion of the Principal Investigator or delegate, affect drug metabolism. History of hypoglycemia in the newborn period requiring glucose infusion rate > 10 mg/kg/min or treatment with glucagon or diazoxide. 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 >3 months of age at the time of enrollment (term HIE patients only) Weight <10%ile based on WHO growth charts at time of initiation of study drug (term HIE patients only). Maternal use of metformin while actively breastfeeding.

Ages Eligible for Study
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Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIE: 20 mg/kg<br> | Drug: Metformin Hydrochloride<br>* Infants will receive 14 consecutive doses, once daily, of metformin, with two dose cohorts. Arm 1: Five infants with HIE will be enrolled on the first dose cohort of 20 mg/kg. Once complete, another five infants will be enrolled on the second dose cohort of 25 mg/kg. Arm 2: Five preterm infants will be enrolled on the first dose cohort of 15 mg/kg. Once complete, another five preterm infants will be enrolled on the second dose cohort of 20 mg/kg.<br>|
| Experimental: HIE: 25 mg/kg<br> | Drug: Metformin Hydrochloride<br>* Infants will receive 14 consecutive doses, once daily, of metformin, with two dose cohorts. Arm 1: Five infants with HIE will be enrolled on the first dose cohort of 20 mg/kg. Once complete, another five infants will be enrolled on the second dose cohort of 25 mg/kg. Arm 2: Five preterm infants will be enrolled on the first dose cohort of 15 mg/kg. Once complete, another five preterm infants will be enrolled on the second dose cohort of 20 mg/kg.<br>|
| Experimental: Preterm: 15 mg/kg<br> | Drug: Metformin Hydrochloride<br>* Infants will receive 14 consecutive doses, once daily, of metformin, with two dose cohorts. Arm 1: Five infants with HIE will be enrolled on the first dose cohort of 20 mg/kg. Once complete, another five infants will be enrolled on the second dose cohort of 25 mg/kg. Arm 2: Five preterm infants will be enrolled on the first dose cohort of 15 mg/kg. Once complete, another five preterm infants will be enrolled on the second dose cohort of 20 mg/kg.<br>|
| Experimental: Preterm: 20 mg/kg<br> | Drug: Metformin Hydrochloride<br>* Infants will receive 14 consecutive doses, once daily, of metformin, with two dose cohorts. Arm 1: Five infants with HIE will be enrolled on the first dose cohort of 20 mg/kg. Once complete, another five infants will be enrolled on the second dose cohort of 25 mg/kg. Arm 2: Five preterm infants will be enrolled on the first dose cohort of 15 mg/kg. Once complete, another five preterm infants will be enrolled on the second dose cohort of 20 mg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with hypoglycemia (serum glucose <3.3mmol/L) | Number of patients with hyperglycemia (glucose>10mmol/L) | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma metformin levels | Pharmacokinetics analysis | 2 weeks | 
| Number of patients who complete study | Feasibility of study intervention administration | 2 weeks | 
| Number of patients who complete all study procedures | Feasibility of executing study operations | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxic Ischemic Encephalopathy, Newborn, Metformin, Prematurity