Hypoxic Ischemic Encephalopathy of Newborn, Premature Birth
Conditions
Keywords
Hypoxic Ischemic Encephalopathy, Newborn, Metformin, Prematurity
Brief summary
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
Interventions
DRUGMetformin Hydrochloride
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.
Sponsors
University of Waterloo
University of Alberta
The Hospital for Sick Children
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 3 Months
Healthy volunteers
No
Inclusion criteria
HIE Patients: 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) Preterm Infants: 1. \<32 weeks gestation at time of birth 2. 36-44 weeks corrected (postmenstrual) gestational age at time of metformin administration 3. Clinical team anticipates hospitalization at SickKids for at least 1 week after study enrollment
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 (term HIE patients only) 6. Weight \<10%ile based on WHO growth charts at time of initiation of study drug (term HIE patients only). 7. Maternal use of metformin while actively breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with hypoglycemia (serum glucose <3.3mmol/L) | 2 weeks | Number of patients with hyperglycemia (glucose\>10mmol/L) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma metformin levels | 2 weeks | Pharmacokinetics analysis |
| Number of patients who complete study | 2 weeks | Feasibility of study intervention administration |
| Number of patients who complete all study procedures | 2 weeks | Feasibility of executing study operations |
Countries
Canada
Outcome results
None listed