In this research study, researchers are evaluating an experimental treatment for very preterm infants with intraventricular hemorrhage (IVH). In this study we want to find out if high doses of Melatonin in combination with Erythropoietin (EPO) are safe for preterm babies.

Background and Goals

The goal of this research study is to see if high doses of melatonin and erythropoietin (EPO) are safely tolerated by preterm babies born before 32 weeks gestation with significant 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.

Study Stages

Step 1 - Completed

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 doses 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 in this trial, then future studies would be needed to see if the drug cocktail is effective. Step 1 of this study was completed.

Step 2 - Current Stage

All infants in Step 2 of this study will be randomized to receive either the study drugs, Melatonin and EPO, or placebo (sterile saline). Three babies will receive Melatonin and EPO for each baby that will receive the placebo. Babies will receive the Melatonin and EPO or placebo from enrollment through the equivalent of 33 weeks gestation.

Standard of Care

All babies who enroll in this study will receive everything we routinely do to optimize a baby’s outcome, which is called the standard of care. 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, 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).

Study Overview

• Study name: Safety of Combined Therapy with Erythropoietin and Melatonin for Very Preterm Infants with Intraventricular Hemorrhage (SCEMPI)
• Study ID: IRB00301237 // NCT 05617833
• Principal investigator: Shenandoah Robinson, M.D.
• Trial phase: Phase 1
• Eligibility criteria: This study is for infants born after 22 weeks and before 32 weeks gestation who have significant brain bleeds known as intraventricular hemorrhage (at least grade II on one side of the brain).
• Clinic location: Neonatal Intensive Care Unit (NICU)s at Johns Hopkins Children's Center and Johns Hopkins Bayview Medical Center in Baltimore, MD and at Johns Hopkins All Children’s Hospital in St. Petersburg, FL.
• Total participants: 53
• How to participate: email [email protected]
• Learn more on ClinicalTrials.gov

What to Expect if Your Child is Selected

The first part of the study will last several weeks after birth while your baby is in the hospital. Your baby will receive the study drugs from enrollment up through 33 weeks gestation. The melatonin (or placebo) is an oral medication. The EPO (or placebo) is given through your baby’s IV line or as an injection through a tiny needle.

Your infant will then be followed for any safety issues for another 4 weeks while they are still in the hospital or at inpatient rehabilitation. This is until your infant has reached almost full term, or around 37 weeks 6 days gestational age. After this time, the study team will call you when your infant is about 6 months old (corrected age) to see if a ventriculoperitoneal shunt has been placed.

While your baby is in the hospital, we will follow the routine weekly bloodwork that is standard for babies born very preterm. We may also collect urine, stool, and blood samples while your baby is receiving the study drug or placebo. Whenever possible we will use leftover blood collected from the routine blood work.

Your infant will be followed as part of routine clinical care in the Infant Neurodevelopment Clinic. Information for the evaluations performed during the clinic visit after two years (corrected) will also be collected for this study. Your infant’s study participation will end following the two-year (corrected) follow-up visit.

Who Can Participate:

A participant must meet these initial criteria:

• Born after 22 weeks gestation and before 32 weeks gestation.
• Have significant intraventricular hemorrhage in the brain found by day of life 21.
• Meet medical criteria and have approval of the neonatologist caring for the baby.

View additional eligibility criteria. This study is not recruiting healthy volunteers.

Benefits and Risks

We cannot guarantee any benefits as a result of taking part in this research study. The study team will discuss the risks associated with taking part in this study.