Metformin Treatment in Infants After Perinatal Brain Injury

Phase 1

Terminated

• Conditions: Hypoxic Ischemic Encephalopathy of Newborn; Premature Birth
• Interventions: Drug: Metformin Hydrochloride

• Registration Number: NCT05590676
• Lead Sponsor: The Hospital for Sick Children

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-10-18
• Study First Submitted QC: 2022-10-18
• Study First Posted: 2022-10-21
• Study Start: 2023-05-02
• Primary Completion: 2024-02-22
• Study Completion: 2024-02-22
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-07

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HIE: 20 mg/kg	Metformin Hydrochloride	-
HIE: 25 mg/kg	Metformin Hydrochloride	-
Preterm: 15 mg/kg	Metformin Hydrochloride	-
Preterm: 20 mg/kg	Metformin Hydrochloride	-

Primary Outcome Measures

Name	Time	Method
Number of patients with hypoglycemia (serum glucose <3.3mmol/L)	2 weeks	Number of patients with hyperglycemia (glucose\>10mmol/L)

Secondary Outcome Measures

Name	Time	Method
Plasma metformin levels	2 weeks	Pharmacokinetics analysis
Number of patients who complete all study procedures	2 weeks	Feasibility of executing study operations
Number of patients who complete study	2 weeks	Feasibility of study intervention administration

Trial Locations

Locations (1)

The Hospital for Sick Children; 🇨🇦 Toronto, Ontartio, Canada