Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin

Prematurity Clinical Trial

— BRITE  

Official title:

Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01207778
• Other study ID #: 10-153
• Secondary ID: R01HD059856
• Status: Completed
• Start date: March 2010
• Est. completion date: December 31, 2020

Study information

• Verified date: May 2022
• Source: University of New Mexico
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Approximately 60,000 premature infants are born each year who weigh less than 1,500 grams,many of whom sustain brain damage because of their prematurity. This study is designed to evaluate the long-term developmental effects of one promising neuroprotective treatment,erythropoietin (Epo), when given in the neonatal period. Using detailed neurodevelopmental testing and state-of-the-art brain imaging, we hope to determine whether this is an effective treatment to prevent brain injury associated with prematurity, and to lay the groundwork for further studies to improve the developmental outcome of infants delivered prematurely.

Description:

Over twelve percent of infants born less than 1,500 grams (VLBW) sustain brain injury with subsequent developmental delay. Although various neuroprotective strategies have been evaluated, none have been successful. One promising intervention is the use of recombinant erythropoietin (Epo, also known as an erythropoiesis stimulating agent, or ESA). In addition to stimulating red cell production, Epo has been shown to be protective in the developing brain in animal models. We have preliminary data suggesting its efficacy when used in VLBW infants, who are at risk of requiring transfusions, and who are also at risk for brain hemorrhage, hypoxicischemic brain injury, and developmental delay. We are currently performing a multicentered study evaluating hematopoietic and short term developmental effects of ESAs in preterm infants randomized to receive Epo, Darbepoetin alfa (a longer acting ESA), or placebo/ control for the first 10 weeks of age (NCT00334737). The first enrolled infants will reach 42-48 months in January, 2010. While that study evaluates the safety and general short-term developmental effects of ESAs, there is an unprecedented opportunity to study long term effects of ESA in significant detail, including evaluating the long term developmental effects and the underlying mechanism of neurologic improvement with state of the art neuroimaging. This proposal seeks to evaluate longitudinal, long-term developmental effects and underlying neurologic mechanisms of ESAs administered to VLBW infants in the first 10 weeks of life. Our specific hypotheses are:

1) ESAs administered to preterm infants during the neonatal period improve long-term neurodevelopmental outcome, 2) ESAs affect regional brain structure, neurochemistry and neurologic organization as reflected in magnetic resonance (MR) imaging, and 3) the blood level of ESA correlates with MR imaging and neurodevelopmental outcome. To test these hypotheses, neurodevelopmental outcome will be assessed through a comprehensive neurodevelopmental assessment at two time points: 42-48 months, and 66-72 months (WPSSI III, Early Child Assessment, Executive Categorization Battery). Brain imaging will be performed concurrent with developmental assessments and includes measures of volume (high resolution volumetric analysis), neurochemistry (magnetic resonance spectroscopy) and regional cerebral blood flow (arterial spin labeling). This study is highly clinically relevant due to the long-term developmental and imaging follow up studies that are part of the design, significantly increasing our ability to determine if developmental, functional and anatomical differences exist in infants randomized to ESAs, a relatively new interventional strategy used in preterm infants. This proposal addresses our long-term goal of developing effective treatment strategies for disorders associated with prematurity through an improved understanding of brain-behavioral relationships.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 36 Months to 72 Months

Eligibility

Inclusion Criteria (preterm):

• birth weight 500-1,250 grams, gestational age =32 weeks

• hematocrit =55%

• =48 hours of age

• expected to survive greater than 72 hours

• consent signed by parent or guardian

Inclusion Criteria (term):

Former term born infants will be eligible if they have not experienced any episodes of hypoxia, hypoglycemia, hyperbilirubinemia, prenatal drug exposure, or sepsis.

Exclusion Criteria (former preterms):

• hemorrhagic or hemolytic disease

• major congenital anomalies (such as trisomy 13, 18 or 21)

• major neurologic abnormality such as hydrocephalus or meningomyelocele

• complex congenital heart disease

• receiving Epo or are enrolled in an Epo study

• evidence of disseminated intravascular coagulation

• clinical seizures are present

• congenital thrombotic disease is suspected

• systolic blood pressures >100 mm Hg (while not on pressor support) Infants with minor anomalies such as clinodactyly, single umbilical vessel or patent ductus are not excluded

Exclusion criteria (term):

hypoxia, hypoglycemia, hyperbilirubinemia, prenatal drug exposure, or sepsis

Related Conditions & MeSH terms

• Premature Birth
• Prematurity

Locations

Country	Name	City	State
United States	MIND Research Network	Albuquerque	New Mexico
United States	UNM	Albuquerque	New Mexico
United States	University of Utah	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
University of New Mexico	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Full Scale IQ, Performance IQ, Verbal IQ, Executive Function	Infants who received ESAs during their initial hospitalization will perform significantly better on measures of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) full scale IQ, performance IQ, verbal IQ, and executive function. Scores are standardized, 100 is an average score with a standard deviation of 15. Higher scores are better. Test scores range from 41 to 160.	42-48 months and 66-72 months