Metformin Treatment in Infants After Perinatal Brain Injury

NCT ID: NCT05590676

Last Updated: 2024-03-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-02
• Study Completion Date: 2024-02-22

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

Conditions

Hypoxic Ischemic Encephalopathy of Newborn; Premature Birth

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HIE: 20 mg/kg

Group Type: EXPERIMENTAL

Metformin Hydrochloride

Intervention Type: DRUG

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.

HIE: 25 mg/kg

Group Type: EXPERIMENTAL

Metformin Hydrochloride

Intervention Type: DRUG

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.

Preterm: 15 mg/kg

Group Type: EXPERIMENTAL

Metformin Hydrochloride

Intervention Type: DRUG

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.

Preterm: 20 mg/kg

Group Type: EXPERIMENTAL

Metformin Hydrochloride

Intervention Type: DRUG

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.

Interventions

Metformin 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Maximum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Waterloo

OTHER

Sponsor Role: collaborator

University of Alberta

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: lead

Responsible Party

Brian Kalish

Staff Neonatologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian T Kalish, MD

Role: PRINCIPAL_INVESTIGATOR

The Hospital for Sick Children

Locations

The Hospital for Sick Children

Toronto, Ontartio, Canada

Countries

Canada

Other Identifiers

3987

Identifier Type: -

Identifier Source: org_study_id