PrematurityBRITENCT01207778
Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin
An observational study of Prematurity, run by University of New Mexico at 3 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 36 to 72 monthsHealthy volunteers can take part
- Conditions the study is for
- Prematurity
- How many people
- 77 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2010to 31 Dec 2020
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 36 to 72 months
- All sexes
- Healthy volunteers accepted
- Child
Study population: All infants previously enrolled in NCT00334737, a randomized masked study of darbepoetin administration in preterm infants, are eligible for the study. In addition we will enroll term infants matched for age, gender and ethnicity to the preterm group to serve as healthy controls.
Who may be able to join
- 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
- Former term born infants will be eligible if they have not experienced any episodes of hypoxia, hypoglycemia, hyperbilirubinemia, prenatal drug exposure, or sepsis.
Who cannot join
- 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
Show all 10Show fewer
- 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
- hypoxia, hypoglycemia, hyperbilirubinemia, prenatal drug exposure, or sepsis
Trial locations and contacts
3 sites in 1 country.
United States3 sites
MIND Research Network
Albuquerque, New Mexico, 87131
UNM
Albuquerque, New Mexico, 87131
University of Utah
Salt Lake City, Utah, 84108
About this study
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.
Read the 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:
- 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.
- Conditions
- Prematurity
- Keywords
- brain, development, erythropoietin, neuroprotection, MRI
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| preterm ESA recipients | Former preterm 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 | Former preterm infants 500-1250 grams who received placebo (sham dosing), from first week of life through 35 weeks corrected gestation | |
| term controls | Former term infants with normal delivery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 42-48 months and 66-72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2010 (estimated)
- Study startMar 2010
- Primary completion31 Dec 2016
- Study completion31 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of New Mexico
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Robin K Ohls, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01207778
- Sponsor's protocol ID
- 10-153
- Other IDs
- R01HD059856
- Acronym
- BRITE
- Status last verified
- May 2022
- First submitted
- 21 Sep 2010
- Last updated
- 4 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Plan to submit data if possible for meta analyses
Publications
Lowe JR, Rieger RE, Moss NC, Yeo RA, Winter S, Patel S, Phillips J, Campbell R, Baker S, Gonzales S, Ohls RK. Impact of Erythropoiesis-Stimulating Agents on Behavioral Measures in Children Born Preterm. J Pediatr. 2017 May;184:75-80.e1. doi: 10.1016/j.jpeds.2017.01.020. Epub 2017 Feb 6.
PubMed 28185625Ohls 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.
PubMed 26908704
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Brain Imaging and Developmental Follow up of Infants Treated With Erythropoietin
- ClinicalTrials.gov ID
- NCT01207778
- Acronym / sponsor ID
- BRITE / 10-153
- Conditions
- Prematurity
- Keywords
- brain, development, erythropoietin, neuroprotection, MRI
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- University of New MexicoUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Mar 2010
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 31 Dec 2020 (actual)
- First posted
- 23 Sep 2010 (estimated)
- Results
- Posted 4 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| preterm ESA recipients | – | –Former preterm 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 | – | –Former preterm infants 500-1250 grams who received placebo (sham dosing), from first week of life through 35 weeks corrected gestation |
| term controls | – | –Former term infants with normal delivery |
Who may qualify
- Ages
- 36 to 72 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- All infants previously enrolled in NCT00334737, a randomized masked study of darbepoetin administration in preterm infants, are eligible for the study. In addition we will enroll term infants matched for age, gender and ethnicity to the preterm group to serve as healthy controls.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Full Scale IQ, Performance IQ, Verbal IQ, Executive Function
Time frame: 42-48 months and 66-72 months
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28185625Lowe JR, Rieger RE, Moss NC, Yeo RA, Winter S, Patel S, Phillips J, Campbell R, Baker S, Gonzales S, Ohls RK. Impact of Erythropoiesis-Stimulating Agents on Behavioral Measures in Children Born Preterm. J Pediatr. 2017 May;184:75-80.e1. doi: 10.1016/j.jpeds.2017.01.020. Epub 2017 Feb 6.
- Derived from this study: PubMed 26908704Ohls 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.
- Individual participant dataSharing planned: Undecided. Plan to submit data if possible for meta analyses
Related trials for Prematurity
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Optimization of Saturation Targets And Resuscitation Trial (OptiSTART)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robin K Ohls, MD principal investigator
University of Utah
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prematurity, run by University of New Mexico at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Full Scale IQ, Performance IQ, Verbal IQ, Executive Function (time frame: 42-48 months and 66-72 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01207778, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.