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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test whether the drug metformin can improve brain development in infants with hypoxic-ischemic encephalopathy (HIE), a specific type of brain injury. Although typically used for diabetes, metformin might aid in brain repair. The study will focus on infants under 6 months old who showed signs of brain injury on an MRI scan after receiving cooling treatment at birth. Participants must have been born after 35 weeks of pregnancy and must have specific patterns of brain injury visible on their MRI. This trial will determine if metformin is safe and practical for these infants. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that metformin is likely to be safe for infants?

Previous studies have found that metformin can help repair the brain. Although typically used to treat diabetes, metformin has not been administered to infants before. As a result, these studies do not provide safety information for infants.

This trial is in an early stage and aims to determine if metformin is safe for infants. Early-stage trials typically involve small groups and focus on identifying any side effects. While metformin is generally safe for other age groups, this trial seeks to ensure its safety for infants with brain injury.

If metformin were already approved for other uses, it would suggest some level of safety. However, since this is the first time it is being tested in infants, the study closely monitors for any signs of harm or side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for infant brain injury, which often focus on supportive care and managing symptoms, metformin offers a novel approach by potentially enhancing brain repair mechanisms. Metformin is traditionally a diabetes medication, but researchers believe it might aid in neuroprotection and neuroregeneration by activating pathways involved in brain cell recovery. This new application is exciting because it could lead to improved outcomes in brain repair, offering hope for more effective therapies for infants with brain injuries.

What evidence suggests that metformin might be an effective treatment for infant brain injury?

Research has shown that metformin, initially used for diabetes, may aid brain healing after injury. Studies have found that metformin can reduce brain damage, such as swelling and tissue loss, shortly after an injury. It also appears to aid in the recovery of movement and cognitive skills when used later. In this trial, participants will receive metformin to evaluate its potential benefits for infants with hypoxic-ischemic encephalopathy (HIE), as it has not been widely tested in babies yet. These findings suggest it might improve brain health in this population. ^{2 3 4 6 7}

Who Is on the Research Team?

Brian Kalish, MD

Principal Investigator

Boston Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. bmjpaedsopen.bmj.com bmjpaedsopen.bmj.com/content/9/1/e002784

Safety and feasibility trial protocol of metformin in infants ... Metformin is an antidiabetic drug that has shown promise to promote recovery after brain injury, but it has not been widely used in infants or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5650422/

Metformin treatment after the hypoxia-ischemia attenuates ... Here, we found that metformin treatment remarkably attenuated brain infarct volumes and brain edema at 24 h after HI injury, and the neuroprotection of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05590676

Metformin Treatment in Infants After Perinatal Brain Injury It identifies the role of the intervention that participants receive. Types of arms include experimental arm, active comparator arm, placebo comparator arm, ...

4. medrxiv.org medrxiv.org/content/10.1101/2024.05.26.24307924v1

A Safety and Feasibility Trial Protocol of Metformin in ... Metformin is an anti-diabetic drug that has shown promise to promote recovery after brain injury, but it has not been widely used in infants or ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666354620300843

Subacute metformin treatment reduces inflammation and ... Our data indicate that delaying metformin treatment to the subacute stage post-injury results in motor and cognitive recovery. Further, metformin treatment ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40850908/

Safety and feasibility trial protocol of metformin in infants ... The antidiabetic drug metformin has recently been recognised as a neurorestorative agent, but, to date, has not been used in infants.

7. ctv.veeva.com ctv.veeva.com/study/a-safety-and-feasibility-trial-protocol-of-metformin-in-infants-after-perinatal-brain-injury

A Safety and Feasibility Trial Protocol of Metformin in Infants ... Infants with hypoxic-ischemic encephalopathy (HIE) are at high risk for neurodevelopmental impairment, despite current standards of care.