In this research study – Safety of Combined Therapy with Erythropoietin and Melatonin for Very Preterm Infants with Intraventricular Hemorrhage (SCEMPI) – 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.

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. 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 research study 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.

All infants in Step 1 of this study will receive the study drugs, Melatonin and EPO in combination from enrollment up through the equivalent of 33 weeks gestation.

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 research study 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).

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
• Total participants: 53
• How to participate: please email [email protected]
• Learn more on ClinicalTrials.gov

What to Expect if Your Child is Selected

The first part of the study with drug dosing will last several weeks after birth while your baby is in the hospital. 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 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.

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 infants study participation will end following the two-year (corrected) follow-up visit.

Overall, you may expect 1 follow-up phone call (6 months corrected age)

Who Can Participate:

A participant must meet all four initial criteria:

• born after 22 weeks gestation
• born before 32 weeks gestation
• be less than 21 days old
• have significant intraventricular hemorrhage in the brain found within the previous 18 days

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.