Headed up by Professor Nikki Robertson, we are a team of Doctors, Midwives and Medical staff - Committed to improving the outcomes for babies born with HIE.
Hypoxic-Ischaemic Encephalopathy (HIE) is a condition that occurs when a baby suffered from a lack of oxygen (hypoxic) or reduced blood flow (ischaemic) impacting the brain (encephalopathy) around the time of birth.
The only treatment currently available to protect the brain after injury is cooling (also called therapeutic hypothermia). Cooling has been shown to reduce further brain injury from HIE. While cooling can reduce the injury caused by HIE, some babies still have long-term problems. The long-term effects of brain injury may include delay in reaching developmental milestones, and difficulties with learning, thinking, speaking and moving (sometimes called cerebral palsy). To improve outcomes for babies with HIE, it is important to explore other treatments that can work alongside cooling.
We are researching a new treatment – melatonin, to treat babies with HIE. The ACUMEN study is a first-in-human, multi-centre study to understand the best and safest dose of melatonin we should give babies for HIE. However, babies with HIE might not absorb melatonin well if taken by mouth and melatonin needs to be given through a vein. This will be the first time we will be giving this melatonin preparation to babies alongside cooling for HIE.
Melatonin is a natural hormone our body makes to help regulate sleep. It is safe and is used in children to treat sleep problems when taken by mouth. However, since babies with HIE might not absorb melatonin well if taken by mouth, we need to give melatonin directly into the bloodstream through the vein (intravenous - IV).
Melatonin is a potential new treatment for HIE. Multiple research studies in animals have demonstrated that high doses of melatonin alongside cooling can provide better brain protection compared to cooling alone. Results from these studies show that, for melatonin to work well, high levels of melatonin in the blood (15-30mg/L) are needed within 6-8h of baby being born. These levels are much higher than the natural levels of melatonin the body makes (about 10,000 times higher). However, its effectiveness in babies is not yet known, and this study aims to find out whether melatonin can be safely given to newborns and whether it reaches the levels in the blood that were found to be beneficial in multiple animal studies.
To make melatonin into a liquid form, we needed to add a chemical that helps melatonin dissolve (called an excipient). In this melatonin preparation, a small amount of ethanol (alcohol) is used. This is already found in other common medicines used in newborn care (e.g., furosemide, iron, phenobarbital). Preclinical research shows that ethanol can also help protect the brain, which is why it is included as an “adjuvant” (helpful) excipient. After each dose of the study drug, your baby’s blood alcohol levels will be checked alongside melatonin levels to ensure they stay below a limit deemed to be safe (below 0.25 g/L).
Babies will receive the same standard clinical care for all babies with HIE (including standard cooling). As part of the ACUMEN study, babies will also receive 6 doses of melatonin during cooling. Melatonin is given through the vein (intravenously) and the first dose needs to be given within 6 hours of birth over 2 hours. The next 5 doses will be given every 12 hours from 24 hours. Babies are initially given a small amount of melatonin. Over the duration of the full research study, we will be increasing the dose until we find the best dose of melatonin to give for HIE.
Babies will receive detailed monitoring of the brain (as part of their standard care) including monitoring of the brain activity (using EEG - Electroencephalography), brain tissue oxygen levels (using NIRS - near infrared spectroscopy), and detailed brain scan (MRI scan) which will also measure the chemical changes in the brain after HIE (MRS - Magnetic Resonance Spectroscopy).
As part of the study, there will be additional blood tests to measuring melatonin and ethanol levels as well as an optional "biomarker study". This biomarker study will help us understand HIE better and develop new tests for this condition. Participation in this exploratory biomarker research is optional and will not affect participation in the rest of the study.
Your baby will be followed up for 3-months as part of the ACUMEN study.
Babies may be eligible to take part in the ACUMEN trial if they have been diagnosed with moderate-severe HIE within the first six hours after birth. Our expert clinical teams at participating hospitals will carefully assess each baby to see if they meet the criteria for the trial. If your baby is eligible, a member of the research team will explain everything you need to know, answer your questions, and discuss whether participation is right for your baby. Even if your baby is eligible, deciding to participate is completely up to you, and our team is here to guide and support you through the process.
You can change your mind about your baby’s participation in the study at any time and without giving a reason. Your study doctor can advise you about any concerns you may have. A decision to stop taking part at any time will not affect the standard of care your baby receives.
If you have any questions about the trial, please contact the ACUMEN trial team at University College London Comprehensive Clinical Trials unit by emailing: cctu.acumen@ucl.ac.uk
