At Hope for HIE, we are constantly working to bridge families with the latest research, emerging therapies, and the experts who are pushing the field forward. Recently, we sat down with Dr. Brian Kalish, neonatologist, neuroscientist, and Vice Chair of Hope for HIE’s Medical Advisory Board, to learn about a new clinical trial he’s leading at Boston Children’s Hospital.
This study explores the use of metformin—a widely used and well-understood medication—to support brain development and plasticity in infants with HIE. While metformin has been around for decades as a treatment for diabetes, new research suggests it might also help the brain heal and adapt after injury.
Dr. Kalish walked us through the “why,” the “how,” and the hope behind this work.
Missed the live Q&A? No worries. Like any good partner, we took notes and are willing to share!
For Dr. Kalish, the drive to study HIE stems from a deep desire shared by many in the neonatal field: moving beyond survival toward long-term thriving.
“We’ve gotten so much better at saving even our sickest babies,” he shared. “Now we need to ensure they can thrive long after they leave the NICU.”
Even with therapeutic hypothermia—the current standard treatment—many infants with HIE still face challenges in long-term neurodevelopment. Dr. Kalish’s research focuses on finding additional therapies that can support the brain not only in the first hours of life, but also during the critical weeks and months of plasticity that follow.
This belief—that healing continues long after the NICU—is foundational to his work.
Metformin may seem like an unexpected candidate for neonatal brain injury, but it has several qualities that make it promising:
| A long safety history. |
Metformin has been used for over 50 years. Its safety profile in adults, teens, and older children is well understood.
| Growing evidence in brain injury. |
Adults with stroke who were on metformin have shown better outcomes, sparking more research.
| Preclinical studies are encouraging. |
Animal models have shown that metformin may:
| Early pediatric research. |
Previous studies in older children exposed to brain injury (like cranial radiation) found signals that metformin may help improve outcomes.
Seeing these threads weave together, Dr. Kalish began to ask the question: Could metformin help promote brain plasticity and resilience for infants with HIE?
Most HIE therapies focus on the immediate hours and days after birth. Dr. Kalish’s study is different.
Its aim is to support the brain during the longer window of plasticity—the time when babies are home, growing, learning, and adapting.
This is the first study to give metformin to young infants, beginning between 3–6 months of age, with the goal of enhancing the brain’s ability to repair and rewire after injury.
“Ultimately, what happens in the weeks to months after a baby goes home is at least as important as what happens in the NICU,” Dr. Kalish emphasized.
Safety is the cornerstone of this trial. Several safeguards are built in:
Hope for HIE leadership and parents with lived experience were involved early in designing the study to ensure it was family-friendly, feasible, and sensitive to the needs of our community.
The trial is regulated and approved by the FDA, requiring detailed monitoring plans and regular reporting.
Dr. Kalish’s team spent a full year using advanced pharmacokinetic modeling to calculate a dose safe for infants.
Families receive:
While metformin is not expected to cause low blood sugar or lab abnormalities in this population, these checks help ensure safety every step of the way.
The trial is currently enrolling at Boston Children’s Hospital. Families from anywhere can participate if they’re able to travel to Boston for three in-person visits.
Infants take metformin for 12 weeks, beginning at a low dose and gradually increasing to a full target dose.
Families come to Boston Children’s Hospital for three study visits:
The main goals of this stage of research are to determine:
With this foundation, future studies could begin earlier in life and follow children longer.
Dr. Kalish emphasizes that no single medication is likely to be a “cure” for HIE. Instead, he imagines a future where infants receive a cocktail of interventions across multiple time points—from the NICU through early infancy—to maximize developmental potential.
Metformin, he hopes, may become one of the tools available to support babies during a period of extraordinary brain growth.
And while this study is beginning at one site, success here could lead to multi-center trials across the country and eventually the world.
Families interested in the study can reach out directly to Dr. Kalish (email: Brian.Kalish@childrens.harvard.edu), who welcomes questions and conversations with parents exploring whether participation might be right for their child.
Dr. Kalish also created a short YouTube video explaining the study to families interested in participating.
The full clinical trial overview can be found here.
Dr. Kalish left us with a message of both realism and optimism:
“We're not looking for a silver bullet. But we hope this becomes one more arrow in the quiver—one more way we can help children with HIE thrive.”
At Hope for HIE, we are grateful for researchers like Dr. Kalish who tirelessly pursue new avenues of support and healing for our families. We will continue to update our community as this important work progresses.
To watch the full Q&A with Dr. Kalish or to read our key takeaways at a glance, click the buttons below!
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