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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University of New Mexico
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of New Mexico
ClinicalTrials.gov Identifier:
NCT01207778
First received: September 21, 2010
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

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.


Condition
Prematurity

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin

Resource links provided by NLM:


Further study details as provided by University of New Mexico:

Primary Outcome Measures:
  • neurocognition [ Time Frame: 42-48 months and 66-72 months ] [ Designated as safety issue: No ]
    Infants who received ESAs during their initial hospitalization will perform significantly better on measures of general cognition, executive function, language, and visual motor skills


Secondary Outcome Measures:
  • Brain imaging [ Time Frame: 42-48 months and 66-72 months ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 136
Study Start Date: March 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

Detailed 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 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.

  Eligibility

Ages Eligible for Study:   6 Months to 47 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

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.

Criteria

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 PDA are not excluded

Exclusion criteria (term):

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01207778

Contacts
Contact: Robin K Ohls, MD 505-272-6410 rohls@salud.unm.edu
Contact: Sean Gonzales 505-272-6837 sgonzales@mrn.org

Locations
United States, New Mexico
MIND Research Network Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Sarah Peceny    505-272-6837    speceny@mrn.org   
Principal Investigator: John Phillips, MD         
UNM Recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Jean Lowe, PhD    505-272-6752    jrlowe@unm.edu   
Sub-Investigator: Jean Lowe, PhD         
United States, Utah
PCMC/University of Utah Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Susan Wiedmeier, MD    801-213-3298    susan.wiedmeier@imail.org   
Contact: Karen Osborne, RN    801-213-3298    karen.osborne@hsc.utah.edu   
Principal Investigator: Susan Wiedmeier, MD         
Sponsors and Collaborators
University of New Mexico
Investigators
Principal Investigator: Robin K Ohls, MD University of New Mexico
  More Information

No publications provided

Responsible Party: University of New Mexico
ClinicalTrials.gov Identifier: NCT01207778     History of Changes
Other Study ID Numbers: 10-153, R01HD059856
Study First Received: September 21, 2010
Last Updated: September 9, 2014
Health Authority: United States: UNM Institutional Review Board

Keywords provided by University of New Mexico:
brain
development
erythropoietin
neuroprotection
MRI

Additional relevant MeSH terms:
Epoetin alfa
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014