Metformin for Infant Brain Injury

Overseen By Kate Eident, BS

Age: < 18

Sex: Any

Trial Phase: Phase 1

Sponsor: Boston Children's Hospital

Must not be taking: Antidiabetics, Steroids, Diuretics, others

Disqualifiers: Genetic disorders, Liver disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

Yes, if your infant is taking any of the listed medications such as anti-diabetic drugs, steroids, diuretics, or certain heart medications, they will need to stop taking them to participate in the trial.

What evidence supports the effectiveness of the drug metformin for infant brain injury?

Research shows that metformin can help repair brain injuries in infants by activating the brain's own repair cells, reducing brain swelling, and improving motor and cognitive functions. It has been effective in animal studies for conditions like hypoxic-ischemic brain injury, which is similar to the type of brain injury being studied in infants. ^{1 2 3 4 5}

Is metformin generally safe for use in humans?

Metformin, commonly used to treat type II diabetes, has been studied for its safety in various conditions, including brain injuries. Research shows it can reduce inflammation and improve brain function in animal models, suggesting it is generally safe for use in humans. ^{1 2 4 6 7}

How does the drug metformin differ from other treatments for infant brain injury?

Metformin is unique because it not only reduces inflammation and brain swelling but also activates the brain's own repair cells, called neural precursor cells, to help heal the brain after injury. Unlike other treatments, it has shown potential to improve both motor and cognitive functions by promoting brain repair and reducing damage in animal models. ^{1 2 3 4 8}

Research Team

Brian Kalish, MD

Principal Investigator

Boston Children's Hospital

Eligibility Criteria

This trial is for infants born after more than 35 weeks of pregnancy who have been diagnosed with hypoxic-ischemic encephalopathy (HIE) and received cooling therapy. It's not suitable for those who don't meet these specific conditions.

Inclusion Criteria

My MRI shows brain injury from lack of oxygen.

My child is under 6 months old and can start the study drug between 3 to 6 months old.

I was born after 35 weeks of pregnancy and received cooling therapy for HIE at birth.

Exclusion Criteria

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.

My brain MRI after cooling treatment shows no signs of damage.

I am currently taking medication for diabetes, blood pressure, seizures, or thyroid issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive metformin with dose escalation over 6 weeks, followed by full dose for another 6 weeks

12 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Metformin

Trial Overview The trial is testing the safety and feasibility of using Metformin, a drug commonly used to treat diabetes, as a potential treatment to improve brain repair and development in infants with HIE.

Participant Groups

Group I: Metformin Intervention Experimental Treatment 1 Intervention

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 (\~25mg/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 Is Running the Clinical Trial?

Boston Children's Hospital

Lead Sponsor

Trials

801

Recruited

5,584,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Delayed metformin treatment improves functional recovery following traumatic brain injury via central AMPK-dependent brain tissue repair. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Subacute metformin treatment reduces inflammation and improves functional outcome following neonatal hypoxia ischemia. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Metformin pretreatment rescues olfactory memory associated with subependymal zone neurogenesis in a juvenile model of cranial irradiation. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

A randomized controlled trial on the efficacy, safety, and pharmacokinetics of metformin in severe traumatic brain injury. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Metformin Reduces Repeat Mild Concussive Injury Pathophysiology. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke. [2022]