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Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin (BRITE)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
University of New Mexico
ClinicalTrials.gov Identifier:
NCT01207778
First received: September 21, 2010
Last updated: January 30, 2017
Last verified: January 2017

September 21, 2010
January 30, 2017
March 2010
December 31, 2016   (Final data collection date for primary outcome measure)
neurocognition [ Time Frame: 42-48 months and 66-72 months ]
Infants who received ESAs during their initial hospitalization will perform significantly better on measures of general cognition, executive function, language, and visual motor skills
Same as current
Complete list of historical versions of study NCT01207778 on ClinicalTrials.gov Archive Site
Brain imaging [ Time Frame: 42-48 months and 66-72 months ]
Compared to former VLBW children who did not receive ESA therapy, VLBW children who did receive ESA therapy will demonstrate lower total cerebral gray/white ratios as determined by morphometric MR analysis, reduced regional cerebral blood flow in the right dorsolateral frontal cortex as determined by arterial spin labeling (ASL), and increased glutamate/glutamine (Glx) in the anterior cingulate gyrus with increased creatine in the left frontal white matter as measured by magnetic resonance spectroscopy
Same as current
Not Provided
Not Provided
 
Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin
Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin
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.

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.

Observational
Observational Model: Case-Control
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:
saliva collected for DNA
Non-Probability Sample
All infants previously enrolled in NCT00334737, a randomized masked study of darbepoetin administration in preterm infants, are eligible for the study. We anticipate enrolling 75 of the original 102 infants from that study. In addition we will enroll 25 preterm infants who did not receive Epo treatment during hospitalization, and 36 term infants matched for age, gender and ethnicity to the preterm group.
Prematurity
Not Provided
  • preterm ESA recipients
    infants 500-1250 grams who received erythropoietin (400 units/kg 3x/week) or darbepoetin (10 micrograms/kg 1x/week), from the first week of life through 35 weeks corrected gestation
  • preterm controls
    preterm infants 500-1250 grams who received placebo (sham dosing), from first week of life through 35 weeks corrected gestation
  • term controls
    Term infants with normal delivery
Ohls RK, Cannon DC, Phillips J, Caprihan A, Patel S, Winter S, Steffen M, Yeo RA, Campbell R, Wiedmeier S, Baker S, Gonzales S, Lowe J. Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin. Pediatrics. 2016 Mar;137(3):e20153859. doi: 10.1542/peds.2015-3859. Epub 2016 Feb 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
105
December 2018
December 31, 2016   (Final data collection date for primary outcome measure)

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):

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

Exclusion Criteria (preterm):

  • 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

Sexes Eligible for Study: All
6 Months to 47 Months   (Child)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01207778
10-153
R01HD059856 ( US NIH Grant/Contract Award Number )
No
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Undecided
Plan to submit data to data and specimen hub (DASH)
University of New Mexico
University of New Mexico
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Robin K Ohls, MD University of New Mexico
University of New Mexico
January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP