Metformin Treatment in Infants After Perinatal Brain Injury
Primary Purpose
Hypoxic Ischemic Encephalopathy of Newborn, Premature Birth
Status
Not yet recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Metformin Hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Hypoxic Ischemic Encephalopathy of Newborn focused on measuring Hypoxic Ischemic Encephalopathy, Newborn, Metformin, Prematurity
Eligibility Criteria
Inclusion Criteria:
- > 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)
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
- Weight <10%ile based on WHO growth charts at time of initiation of study drug.
Sites / Locations
- The Hospital for Sick Children
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
HIE: 20 mg/kg
HIE: 25 mg/kg
Preterm: 15 mg/kg
Preterm: 20 mg/kg
Arm Description
Outcomes
Primary Outcome Measures
Number of patients with hypoglycemia (serum glucose <3.3mmol/L)
Number of patients with hyperglycemia (glucose>10mmol/L)
Secondary Outcome Measures
Plasma metformin levels
Pharmacokinetics analysis
Number of patients who complete study
Feasibility of study intervention administration
Number of patients who complete all study procedures
Feasibility of executing study operations
Full Information
NCT ID
NCT05590676
First Posted
October 18, 2022
Last Updated
March 31, 2023
Sponsor
The Hospital for Sick Children
Collaborators
University of Waterloo, University of Alberta
1. Study Identification
Unique Protocol Identification Number
NCT05590676
Brief Title
Metformin Treatment in Infants After Perinatal Brain Injury
Official Title
A Phase I Safety and Feasibility of Metformin Treatment in Infants After Perinatal Brain Injury
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 10, 2023 (Anticipated)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Hospital for Sick Children
Collaborators
University of Waterloo, University of Alberta
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxic Ischemic Encephalopathy of Newborn, Premature Birth
Keywords
Hypoxic Ischemic Encephalopathy, Newborn, Metformin, Prematurity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HIE: 20 mg/kg
Arm Type
Experimental
Arm Title
HIE: 25 mg/kg
Arm Type
Experimental
Arm Title
Preterm: 15 mg/kg
Arm Type
Experimental
Arm Title
Preterm: 20 mg/kg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Metformin Hydrochloride
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of patients with hypoglycemia (serum glucose <3.3mmol/L)
Description
Number of patients with hyperglycemia (glucose>10mmol/L)
Time Frame
2 weeks
Secondary Outcome Measure Information:
Title
Plasma metformin levels
Description
Pharmacokinetics analysis
Time Frame
2 weeks
Title
Number of patients who complete study
Description
Feasibility of study intervention administration
Time Frame
2 weeks
Title
Number of patients who complete all study procedures
Description
Feasibility of executing study operations
Time Frame
2 weeks
10. Eligibility
Sex
All
Maximum Age & Unit of Time
3 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Brian T Kalish, MD
Phone
416-813-7654
Ext
301433
Email
brian.kalish@sickkids.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Rosanna Yankanah, MSc
Phone
416-813-7654
Ext
202919
Email
rosanna.yankanah@sickkids.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brian T Kalish, MD
Organizational Affiliation
The Hospital for Sick Children
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontartio
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian T Kalish, MD
Phone
416-813-7654
Ext
301433
Email
brian.kalish@sickkids.ca
12. IPD Sharing Statement
Learn more about this trial
Metformin Treatment in Infants After Perinatal Brain Injury
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