Hypoxic-Ischemic EncephalopathyPhase 1NCT06429007
A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury
A Phase 1 study testing Metformin in people with Hypoxic-Ischemic Encephalopathy and HIE, run by Boston Children's Hospital at 1 site in United States.
Trial summary
Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. Read more about this study
- Who is it for?
- Ages 3 to 6 months
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy, HIE, Neurodevelopment
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2025to 1 Mar 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- <6 months old at time of enrollment, and able to initiate study drug between 3 and 6 months old.
- Born > 35 weeks gestational age with a clinical diagnosis of HIE at birth, who receive therapeutic hypothermia.
- Post-hypothermia brain MRI with evidence of hypoxic-ischemic brain injury, based on the neuroradiology clinical report. Specifically, participants must have had evidence of a lactate peak by magnetic resonance spectroscopy and/or signal abnormalities by conventional (T1 and/or T2) or diffusion-weighted images consistent with hypoxic-ischemic pattern of injury.
- English- or Spanish-speaking families, as the parents/guardians will be responsible for documenting dose administrations and adverse events.
Who cannot join
- Known genetic or chromosomal disorder, and in the presence of congenital or acquired liver or kidney disease that might, in the opinion of the Principal Investigator (PI) or delegate, affect drug metabolism.
- Maternal use of metformin while actively breastfeeding.
- Infant weight below the 10th percentile based on WHO growth charts at the time of study drug initiation.
- Normal post-hypothermia brain MRI, without evidence of ischemic brain injury, based on the neuroradiology clinical report.
- Concomitant use of the following drugs: anti-diabetic drugs (insulin, sulfonylureas), steroids, diuretics (furosemide, chlorothiazide, spironolactone), diazoxide, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers (including nifedipine), phenytoin, valproic acid, topiramate, cimetidine, corticosteroids, thyroid medications, sympathomimetics, carbonic anhydrase inhibitors, or any antibiotics.
- Any condition or diagnosis, that could in the opinion of the PI 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE.
- Being tested
- Metformin
- Keywords
- HIE, metformin, Hypoxic-Ischemic Encephalopathy, Pharmacokinetic modeling, Neonates, Brain Injury
- Medical subject headings
- Hypoxia-Ischemia, Brain, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Metformin will be initiated at 25% of the target dose (4 mg/kg administered twice daily, total daily dose 8 mg/kg) for three weeks. In the absence of adverse effects, metformin dose will be escalated to 50% of the target dose (8 mg/kg administered twice daily for a total daily dose of 16mg/kg) for remaining 3 weeks to minimize potential gastrointestinal upset at higher doses. Parents will be documenting adverse events and performing glucometer checks twice a day for 3 days post dose escalation.
Parents will then receive a 6-week supply of metformin at the target dose (16 mg/kg administered twice daily, total daily dose 32 mg/kg). Adverse events will be documented and glucometer checks will be performed twice a day for 3 days following dose escalation.
| Study group | Role | What they receive |
|---|---|---|
| Metformin Intervention | Experimental | Participants will complete a pre-study visit with baseline bloodwork including a complete blood count (CBC), liver and renal function, basic chemistry, glucose, and lactate. At this visit, parents will be taught how to administer metformin and given a 6-week supply (at 25% \& 50% of the target dose for three weeks each) to minimize potential gastrointestinal upset. Parents will be educated on adverse effects and receive a diary to log dose administration and side effects. They will also be asked to perform at-home glucometer checks twice daily for 3 days post the dose escalation. After six weeks, participants will return for a study visit with repeat labs including assessing the levels of vitamin B12 and plasma metformin for measurement of pharmacokinetics. Parents will then receive a 6-week supply of metformin at the full dose (~32mg/kg) for 6 weeks. A final study visit will then occur following 12-weeks of metformin therapy, with repeat labs including plasma metformin levels. Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety profile of kidney function
A renal function panel (chem 10 with renal function) will be performed prior to the initiation of therapy and at all subsequent study visits.
Measured: 12 weeks
Safety profile of liver function
A liver function test (LFT) will be performed prior to the initiation of therapy and at all subsequent study visits.
Measured: 12 weeks
Recruitment feasibility
To assess feasibility, the number of eligible patients will be compared to the number of patients who consent to participate in the study.
Measured: 12 weeks
Secondary outcomes (1)
Validity of neonatal model of metformin pharmacokinetics
Plasma metformin levels will be analyzed by investigators with whole blood obtained at study visits.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2024
- Study start1 Oct 2025
- Primary completion1 Jan 2028 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Kalish, Boston Children's Hospital
- Investigators
- Brian Kalish, MD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06429007
- Sponsor's protocol ID
- IRB-P00048370
- Status last verified
- Feb 2026
- First submitted
- 7 May 2024
- Last updated
- 17 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hutchinson AM, Pais R, Endginton AN, Pilon B, MacDonald JM, MacDonald ME, Lewis T, Offringa M, Kalish BT. Safety and feasibility trial protocol of metformin in infants after perinatal brain injury. BMJ Paediatr Open. 2025 Aug 24;9(1):e002784. doi: 10.1136/bmjpo-2024-002784.
PubMed 40850908
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Feasibility Trial Protocol of Metformin in Infants After Perinatal Brain Injury
- ClinicalTrials.gov ID
- NCT06429007
- Acronym / sponsor ID
- IRB-P00048370
- Keywords
- HIE, metformin, Hypoxic-Ischemic Encephalopathy, Pharmacokinetic modeling, Neonates, Brain Injury
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- 1 Oct 2025 (actual)
- Primary completion
- 1 Jan 2028 (estimated)
- Study completion
- 1 Mar 2029 (estimated)
- First posted
- 24 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care. Adjunctive treatments to promote brain repair are needed. The antidiabetic drug metformin has recently been recognized as a neurorestorative agent, but, to date, has not been used in infants. Herein, the investigator describes a clinical trial with the aim of demonstrating the safety and feasibility of metformin use to improve neurodevelopmental outcomes in infants with HIE.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metformin Intervention | Experimental | Drug: MetforminParticipants will complete a pre-study visit with baseline bloodwork including a complete blood count (CBC), liver and renal function, basic chemistry, glucose, and lactate. At this visit, parents will be taught how to administer metformin and given a 6-week supply (at 25% \& 50% of the target dose for three weeks each) to minimize potential gastrointestinal upset. Parents will be educated on adverse effects and receive a diary to log dose administration and side effects. They will also be asked to perform at-home glucometer checks twice daily for 3 days post the dose escalation. After six weeks, participants will return for a study visit with repeat labs including assessing the levels of vitamin B12 and plasma metformin for measurement of pharmacokinetics. Parents will then receive a 6-week supply of metformin at the full dose (~32mg/kg) for 6 weeks. A final study visit will then occur following 12-weeks of metformin therapy, with repeat labs including plasma metformin levels. |
Who may qualify
- Ages
- 3 to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- <6 months old at time of enrollment, and able to initiate study drug between 3 and 6 months old.
- Born > 35 weeks gestational age with a clinical diagnosis of HIE at birth, who receive therapeutic hypothermia.
- Post-hypothermia brain MRI with evidence of hypoxic-ischemic brain injury, based on the neuroradiology clinical report. Specifically, participants must have had evidence of a lactate peak by magnetic resonance spectroscopy and/or signal abnormalities by conventional (T1 and/or T2) or diffusion-weighted images consistent with hypoxic-ischemic pattern of injury.
- English- or Spanish-speaking families, as the parents/guardians will be responsible for documenting dose administrations and adverse events.
Key exclusion criteria (6 listed)
- Known genetic or chromosomal disorder, and in the presence of congenital or acquired liver or kidney disease that might, in the opinion of the Principal Investigator (PI) or delegate, affect drug metabolism.
- Maternal use of metformin while actively breastfeeding.
- Infant weight below the 10th percentile based on WHO growth charts at the time of study drug initiation.
- Normal post-hypothermia brain MRI, without evidence of ischemic brain injury, based on the neuroradiology clinical report.
- Concomitant use of the following drugs: anti-diabetic drugs (insulin, sulfonylureas), steroids, diuretics (furosemide, chlorothiazide, spironolactone), diazoxide, beta blockers, ACE inhibitors, angiotensin II blockers, calcium channel blockers (including nifedipine), phenytoin, valproic acid, topiramate, cimetidine, corticosteroids, thyroid medications, sympathomimetics, carbonic anhydrase inhibitors, or any antibiotics.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminMetformin will be initiated at 25% of the target dose (4 mg/kg administered twice daily, total daily dose 8 mg/kg) for three weeks. In the absence of adverse effects, metformin dose will be escalated to 50% of the target dose (8 mg/kg administered twice daily for a total daily dose of 16mg/kg) for remaining 3 weeks to minimize potential gastrointestinal upset at higher doses. Parents will be documenting adverse events and performing glucometer checks twice a day for 3 days post dose escalation. Parents will then receive a 6-week supply of metformin at the target dose (16 mg/kg administered twice daily, total daily dose 32 mg/kg). Adverse events will be documented and glucometer checks will be performed twice a day for 3 days following dose escalation. | Drug | Metformin Intervention |
Primary outcome
Safety profile of kidney function
Time frame: 12 weeks
A renal function panel (chem 10 with renal function) will be performed prior to the initiation of therapy and at all subsequent study visits.
Safety profile of liver function
Time frame: 12 weeks
A liver function test (LFT) will be performed prior to the initiation of therapy and at all subsequent study visits.
Recruitment feasibility
Time frame: 12 weeks
To assess feasibility, the number of eligible patients will be compared to the number of patients who consent to participate in the study.
1 secondary outcome
Validity of neonatal model of metformin pharmacokinetics
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2026.
- Derived from this study: PubMed 40850908Hutchinson AM, Pais R, Endginton AN, Pilon B, MacDonald JM, MacDonald ME, Lewis T, Offringa M, Kalish BT. Safety and feasibility trial protocol of metformin in infants after perinatal brain injury. BMJ Paediatr Open. 2025 Aug 24;9(1):e002784. doi: 10.1136/bmjpo-2024-002784.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Brian Kalish, MD principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin in people with Hypoxic-Ischemic Encephalopathy and HIE, run by Boston Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety profile of kidney function (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06429007, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.