Safety of Combined Therapy with Erythropoietin and Melatonin for Preterm Infants with Intraventricular Hemorrhage (SCEMPI)

Location

Johns Hopkins Children’s Center and Johns Hopkins Bayview Medical Center Neonatal Intensive Care Units (NICUs)

Baltimore, Maryland

Background

The Hydrocephalus Association invites you to participate in an NIH-sponsored study currently being conducted by Shenandoah “Dody” Robinson, MD, Professor of Neurosurgery, Neurology and Pediatrics at Johns Hopkins University and the SCEMPI Clinical Trials team, in collaboration with the Johns Hopkins Neurosciences Intensive Care Nursery (NICN). This is the first intervention trial for very preterm newborns with a severe brain bleed (intraventricular hemorrhage) to test the safety of a new 2-drug regimen. The Hydrocephalus Association supported part of the preclinical laboratory work that led to this NIH-funded clinical trial.

Why is this research being done?

The goal of this study is to see if high doses of melatonin and erythropoietin (EPO) are safely tolerated by preterm babies born before 32 weeks gestation with severe brain bleeds.  Both melatonin and EPO are natural hormones essential for healthy brain development.  Prior to birth, the fetus receives melatonin through the placenta.  When born too early, a baby no longer has access to this melatonin supply.  Melatonin in children and adults is best known for regulating the sleep cycle.  Melatonin is also necessary for sustaining basic energy processes in cells, especially during periods of rapid growth and illness like a preterm baby may experience.  Erythropoietin is best known for driving the maturation of red blood cells in the bone marrow.  EPO also is extremely important for guiding the development and maturation of cells in the brain.  Importantly, melatonin and EPO work closely together.  Without an adequate supply of melatonin, EPO is unable to work effectively.  By replacing melatonin and EPO for preterm babies, we hope to support the natural growth and repair processes in the developing brain.  If melatonin and EPO act together, then they may promote healing in the brain, including for the cells that control the flow of cerebrospinal fluid (CSF).  Our eventual goal is to see if this drug combination can reduce the dependence on a shunt to divert the CSF flow.

As a first step, we need to study whether high doses of melatonin and EPO are safe to give preterm babies while the brain is recovering from a brain bleed.  This clinical trial is to learn whether preterm babies can safely tolerate high d

oses of melatonin and EPO when given over several weeks.  This study will not look at whether high doses of melatonin and EPO help babies with brain bleeds recover better- this study is primarily focused on safety. If high doses of melatonin and EPO are found to be safe, then future studies would be needed to see if the drug cocktail is effective.

Study Participants

Who is eligible to participate in this study?

This study is for babies born preterm before 32 weeks gestation who also have a recent significant brain bleed called a high-grade intraventricular hemorrhage (IVH).  To be eligible, a baby needs to meet the following requirements:

Be born after 22 weeks and before 32 weeks.  Babies born before 23 weeks are not eligible.

Be less than 21 days old.

Have a severe brain bleed seen on a head ultrasound that was done within the past 5 days. For this clinical trial, a severe bleed is defined as at least a grade III IVH on at least one side of the brain.

Meet other medical requirements and have the approval of your baby’s primary doctor in the neonatal intensive care unit.

Study Components

What should study participants expect after enrollment?

There is no cost to the patient/family for participating in the study—all costs are covered by the clinical trial or are part of routine clinical care in the neonatal intensive care unit (NICU).  To participate in this clinical trial, a baby must be cared for in the NICU at Johns Hopkins Children’s Center or the NICU at Johns Hopkins Bayview Medical Center.  The same clinical group provides care for babies in both of these Hopkins NICUs.  In some instances, babies in other NICUs in the mid-Atlantic region may be transferred to one of the NICUs at Johns Hopkins to participate in the clinical trial.

Participation is completely voluntary and will not affect the other medical care your baby will receive. You may decide to have your baby stop participating at any time.

The babies in the clinical trial will receive the same routine clinical care as other babies who are born preterm and have a significant brain bleed.  In the Johns Hopkins NICUs in Baltimore, this care includes the following:

• Routine medical care in the NICU.
• Weekly blood tests as needed.
• Repeat head ultrasounds to follow the brain’s recovery.
• Neurodevelopmental examinations typically at 34 and 36 weeks gestation, and as needed.
• A neonatal Brain MRI near term-equivalent age (when the baby was due to be born).

In addition to the above routine clinical care, babies in the study will receive the study drugs melatonin and erythropoietin (EPO).  In the first part of the study, all babies will receive the drugs from enrollment up to 34 weeks gestation.  In the second part of the study, babies will be randomized to receive either melatonin and EPO or a placebo. The placebo is a special form of water (saline) without the drug present.  The study has been designed so that 3 babies will receive the study drug combination for every 1 baby that receives the placebo.  The second part of the clinical trial will allow us to tell if any side effects that are observed are really due to the drugs or not.

The melatonin is a liquid medicine that will be given each evening. To receive the melatonin, your baby will need to tolerate at least partial feeding via the gut. If the feedings are held, the melatonin will be held too, and then restarted once feedings resume.

The EPO is given by injection.  The first 10 doses of EPO will be given every 48 hours.  After the first 10 doses, the EPO will be given every Monday, Wednesday and Friday.

For babies enrolled in the study, we will collect small blood samples to test for melatonin and EPO blood levels.  Whenever possible, we will use leftover blood that was collected for routine blood tests. When available, we will also collect occasional urine samples to match with the information obtained from the blood samples.

The study drug (melatonin and EPO) will be given from enrollment through 33 weeks gestation and then stop.  From 34 weeks through 37 weeks gestation, the study team will monitor your baby for any potential side effects.  The main part of your baby’s participation ends at that time.

When your baby is 6 months old (corrected for preterm birth), the study team will check if your baby has a permanent shunt. This may be by chart review or a phone call.  Babies born before 32 weeks, especially those with brain bleeds, are typically followed by a special team that monitors the baby’s neurodevelopmental milestones.  The team recommends extra therapies, such as physical and speech therapy, if needed. If your baby participates in this clinical trial, we will offer a neurodevelopmental examination at two years (corrected for preterm birth) to evaluate your baby’s progress in meeting their milestones.

Sign Up!

To participate or get more information, visit the Johns Hopkins SCEMPI Clinical Trial page at : www.hopkinsmedicine.org/SCEMPI

If you have any additional questions, you can also email us at: SCEMPIstudy@jhmi.edu.

For interested patients or families, the research staff will then provide more information including consent documents and further instructions.

Additional Information

Study PI: Shenandoah (Dody) Robinson, MD
Study Coordinator: Kathryn (Katie) Lowe
SCEMPI opened in January 2024.  NCT05617833