Neonatal Congenital Heart DiseaseCHD BrainNCT00932633
Magnetic Resonance Imaging (MRI) to Evaluate Brain Injury in Congenital Heart Disease
An observational study of Neonatal Congenital Heart Disease, run by Emory University at 1 site in United States.
Trial summary
Infants with congenital heart disease (CHD) requiring surgery frequently have brain injury seen on magnetic resonance imaging (MRI). This occurs in approximately 40% of these newborns, and even though these are full-term infants, the injury seen closely resembles the same form of brain injury that can be seen in… Read more about this study
- Who is it for?
- Ages Up to 30 days
- Conditions the study is for
- Neonatal Congenital Heart Disease
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Jan 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Up to 30 days
- All sexes
- No healthy volunteers
- Child
Study population: newborns with congenital heart disease requiring surgery during the first 30 days of life
Who may be able to join
- Term or near-term (> 35 week gestation) neonates with CHD presenting for cardiac surgery
- Less than 30 days old
- No patient will be excluded because of race or ethnicity
- Parental or legal guardian consent will be obtained for all patients prior to enrollment
Who cannot join
- Newborns with multiple organ abnormalities in addition to their heart defect such as diaphragmatic hernia, tracheo-esophageal fistula, and congenital syndromes will be excluded from participation
- Newborns with either genetic syndromes or congenital infections that are associated with developmental delay will also be excluded
- Newborns with perinatal depression as defined by a cord blood gas pH < 7.0 or a 5 minute Apgar score < 5, will be excluded
- Patients with multiple organ failure, syndromes, and perinatal depression have other causes for neurodevelopmental abnormalities
- Those patients unable to return for postoperative follow-up and neurodevelopmental testing will also be excluded from participation
- Parent or legal guardian unable or unwilling to consent
- Non-English speaking families
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
About this study
Official title: Role of Inflammatory Response in Brain Injury Following Neonatal Cardiac Surgery
Infants with congenital heart disease (CHD) requiring surgery frequently have brain injury seen on magnetic resonance imaging (MRI). This occurs in approximately 40% of these newborns, and even though these are full-term infants, the injury seen closely resembles the same form of brain injury that can be seen in premature babies. Much like premature newborns, infants with CHD also have long-term neurodevelopmental problems (in over 50%).
The investigators do not know why infants with CHD get this specific form of brain injury. One risk factor is felt to be the inflammation that occurs in response to heart-lung bypass (cardiopulmonary bypass, or CPB), a necessary feature of open-heart surgery. Newborns have a stronger inflammatory reaction to CPB than older children or adults. The investigators do know from animal experiments and other human data that inflammation can be harmful to the developing brain.
Read more
The investigators hypothesize that children with CHD requiring surgery as a newborn have brain injury due to toxicity from the inflammatory response. The investigators will test this by enrolling newborns undergoing heart surgery to measure markers of inflammation, measure brain injury by MRI, and then test their developmental outcome at 1 and 2 years of age.
An association between inflammation and injury might impact what medicines are chosen to protect the brain in future studies, even in other populations such as preterm infants.
Read the detailed description
Term infants with congenital heart disease (CHD) requiring neonatal surgery have an unusual susceptibility to white matter injury (WMI), a neuropathology typically seen in preterm infants. The mechanism of this brain injury is unclear. Newborns with CHD may experience a dramatic peri-operative inflammatory response during critical periods of neurodevelopment. Experimental models suggest certain pro-inflammatory cytokines can be toxic to developing oligodendrocytes, resulting in white matter pathology. The consequence of exposure to the systemic inflammatory response (SIR) in this group of patients is unknown; however, neuroimaging abnormalities (seen in approximately 40%) and neurodevelopmental impairment (noted in approximately 50%) are both well established in children with CHD. We hypothesize that term newborns with complex CHD requiring neonatal surgery have WMI due to neurotoxicity from the profound peri-operative inflammatory response. These hypotheses will be tested in a prospective longitudinal study that will characterize the SIR (Aim 1) in a heterogeneous group of congenital lesions/surgeries, assess brain injury in the post-operative period (Aim 2), asses neurodevelopment outcomes at 1 and 2 years (Aim 3), and determine whether inflammation plays a mechanistic role (Aim 2a, 3a).
- Conditions
- Neonatal Congenital Heart Disease
- Keywords
- neonatal brain injury, congenital heart disease, magnetic resonance imaging, cardiopulmonary bypass, neurodevelopmental outcome
- Medical subject headings
- Heart Defects, Congenital
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be a measure of the association of pro-inflammatory cytokines with WMI score
Measured: 5 years
Secondary outcomes (2)
Association between inflammatory response and neurodevelopmental testing
Measured: 5 years
Association of neuroimaging abnormalities with neurodevelopmental testing
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2009 (estimated)
- Study startAug 2009
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neonatal Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Responsible party
- Principal investigator, William T. Mahle, MD, Emory University
- Investigators
- William T Mahle, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00932633
- Sponsor's protocol ID
- IRB00017965
- Other IDs
- 17965
- Acronym
- CHD Brain
- Status last verified
- Feb 2016
- First submitted
- 1 Jul 2009
- Last updated
- 10 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Inflammatory Response in Brain Injury Following Neonatal Cardiac Surgery
- ClinicalTrials.gov ID
- NCT00932633
- Acronym / sponsor ID
- CHD Brain / IRB00017965
- Conditions
- Neonatal Congenital Heart Disease
- Keywords
- neonatal brain injury, congenital heart disease, magnetic resonance imaging, cardiopulmonary bypass, neurodevelopmental outcome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Children's Healthcare of Atlanta
- Study start
- Aug 2009
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 3 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infants with congenital heart disease (CHD) requiring surgery frequently have brain injury seen on magnetic resonance imaging (MRI). This occurs in approximately 40% of these newborns, and even though these are full-term infants, the injury seen closely resembles the same form of brain injury that can be seen in premature babies. Much like premature newborns, infants with CHD also have long-term neurodevelopmental problems (in over 50%).
The investigators do not know why infants with CHD get this specific form of brain injury. One risk factor is felt to be the inflammation that occurs in response to heart-lung bypass (cardiopulmonary bypass, or CPB), a necessary feature of open-heart surgery. Newborns have a stronger inflammatory reaction to CPB than older children or adults. The investigators do know from animal experiments and other human data that inflammation can be harmful to the developing brain.
The investigators hypothesize that children with CHD requiring surgery as a newborn have brain injury due to toxicity from the inflammatory response. The investigators will test this by enrolling newborns undergoing heart surgery to measure markers of inflammation, measure brain injury by MRI, and then test their developmental outcome at 1 and 2 years of age.
An association between inflammation and injury might impact what medicines are chosen to protect the brain in future studies, even in other populations such as preterm infants.
Detailed description
Term infants with congenital heart disease (CHD) requiring neonatal surgery have an unusual susceptibility to white matter injury (WMI), a neuropathology typically seen in preterm infants. The mechanism of this brain injury is unclear. Newborns with CHD may experience a dramatic peri-operative inflammatory response during critical periods of neurodevelopment. Experimental models suggest certain pro-inflammatory cytokines can be toxic to developing oligodendrocytes, resulting in white matter pathology. The consequence of exposure to the systemic inflammatory response (SIR) in this group of patients is unknown; however, neuroimaging abnormalities (seen in approximately 40%) and neurodevelopmental impairment (noted in approximately 50%) are both well established in children with CHD. We hypothesize that term newborns with complex CHD requiring neonatal surgery have WMI due to neurotoxicity from the profound peri-operative inflammatory response. These hypotheses will be tested in a prospective longitudinal study that will characterize the SIR (Aim 1) in a heterogeneous group of congenital lesions/surgeries, assess brain injury in the post-operative period (Aim 2), asses neurodevelopment outcomes at 1 and 2 years (Aim 3), and determine whether inflammation plays a mechanistic role (Aim 2a, 3a).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- Up to 30 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- newborns with congenital heart disease requiring surgery during the first 30 days of life
Key inclusion criteria (4 listed)
- Term or near-term (> 35 week gestation) neonates with CHD presenting for cardiac surgery
- Less than 30 days old
- No patient will be excluded because of race or ethnicity
- Parental or legal guardian consent will be obtained for all patients prior to enrollment
Key exclusion criteria (7 listed)
- Newborns with multiple organ abnormalities in addition to their heart defect such as diaphragmatic hernia, tracheo-esophageal fistula, and congenital syndromes will be excluded from participation
- Newborns with either genetic syndromes or congenital infections that are associated with developmental delay will also be excluded
- Newborns with perinatal depression as defined by a cord blood gas pH < 7.0 or a 5 minute Apgar score < 5, will be excluded
- Patients with multiple organ failure, syndromes, and perinatal depression have other causes for neurodevelopmental abnormalities
- Those patients unable to return for postoperative follow-up and neurodevelopmental testing will also be excluded from participation
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
The primary outcome will be a measure of the association of pro-inflammatory cytokines with WMI score
Time frame: 5 years
2 secondary outcomes
Association between inflammatory response and neurodevelopmental testing
Time frame: 5 years
Association of neuroimaging abnormalities with neurodevelopmental testing
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
- Individual participant dataSharing planned: Undecided
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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.
William T Mahle, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neonatal Congenital Heart Disease, run by Emory University at 1 site 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 4 inclusion and 7 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 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary outcome will be a measure of the association of pro-inflammatory cytokines with WMI score (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Feb 2016.