NCT05590676

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

Trial Health

57
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2023

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 18, 2022

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 21, 2022

Completed
6 months until next milestone

Study Start

First participant enrolled

May 2, 2023

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 22, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 22, 2024

Completed
Last Updated

March 7, 2024

Status Verified

March 1, 2024

Enrollment Period

10 months

First QC Date

October 18, 2022

Last Update Submit

March 5, 2024

Conditions

Hypoxic Ischemic Encephalopathy of NewbornPremature Birth

Keywords

Hypoxic Ischemic EncephalopathyNewbornMetforminPrematurity

Outcome Measures

Primary Outcomes (1)

  • Number of patients with hypoglycemia (serum glucose <3.3mmol/L)

    Number of patients with hyperglycemia (glucose\>10mmol/L)

    2 weeks

Secondary Outcomes (3)

  • Plasma metformin levels

    2 weeks

  • Number of patients who complete study

    2 weeks

  • Number of patients who complete all study procedures

    2 weeks

Study Arms (4)

HIE: 20 mg/kg

EXPERIMENTAL
Drug: Metformin Hydrochloride

HIE: 25 mg/kg

EXPERIMENTAL
Drug: Metformin Hydrochloride

Preterm: 15 mg/kg

EXPERIMENTAL
Drug: Metformin Hydrochloride

Preterm: 20 mg/kg

EXPERIMENTAL
Drug: Metformin Hydrochloride

Interventions

Metformin HydrochlorideDRUG

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: 20 mg/kgHIE: 25 mg/kgPreterm: 15 mg/kgPreterm: 20 mg/kg

Eligibility Criteria

AgeUp to 3 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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
  • weeks corrected (postmenstrual) gestational age at time of metformin administration
  • Clinical team anticipates hospitalization at SickKids for at least 1 week after study enrollment

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The Hospital for Sick Children

Toronto, Ontartio, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Premature BirthHypoxia-Ischemia, Brain

Interventions

Metformin

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesBrain IschemiaCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesHypoxia, BrainVascular DiseasesCardiovascular DiseasesHypoxiaSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Study Officials

  • Brian T Kalish, MD

    The Hospital for Sick Children

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Staff Neonatologist

Study Record Dates

First Submitted

October 18, 2022

First Posted

October 21, 2022

Study Start

May 2, 2023

Primary Completion

February 22, 2024

Study Completion

February 22, 2024

Last Updated

March 7, 2024

Record last verified: 2024-03

Locations

CA(1)