Premature BirthNCT03410810
Childhood Outcomes of Preterm Brain Abnormalities
An observational study of Premature Birth and Neurodevelopmental Disorders, run by Children's Hospital Los Angeles at 1 site in United States.
Trial summary
Prematurely born children are at higher risk of cognitive impairments and behavioral disorders than full-term children. There is growing evidence of significant volumetric and shape abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. Read more about this study
- Who is it for?
- Ages Up to 8 yearsHealthy volunteers can take part
- Conditions the study is for
- Premature Birth, Neurodevelopmental Disorders, Brain Development Abnormality
- What is being tested?
- MRI and Neurodevelopmental/Neuropsychological Assessment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2018to 1 Aug 2025
- 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 8 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Our MRI data will consist of two separate neonatal cohorts. Cohort 1 is an existing dataset of neonates scanned in Pittsburgh as part of a separate completed grant. This cohort was scanned at neonatal equivalent age and will be brought back for childhood neurodevelopmental outcomes at 6-8 years of age. Cohort 2 will be a new prospectively recruited cohort that will be scanned in Los Angeles as part of this proposal and will be brought back for infant neurodevelopmental outcome at 9 and 18 months.
Who may be able to join
- Preterm birth (Gestational Age 21-36 weeks)
- English or Spanish speaking families
- PVL and Grade I and II IVH will be considered
Who cannot join
- Shunt
- Intubation, Cpap, Nasal Ventilation
- Chromosomal/Genetic abnormalities
- Mitochondrial/Metabolic Diseases
- Treatment for extracorporeal membrane oxygenation (ECMO)
- Grade III and IV IVH (optional)
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital Los Angeles
Los Angeles, California, 90027
Kayla Guzman, BS, 323-361-6876, kayguzman@chla.usc.edu
About this study
Official title: Predicting the Early Childhood Outcomes of Preterm Brain Shape Abnormalities
Prematurely born children are at higher risk of cognitive impairments and behavioral disorders than full-term children. There is growing evidence of significant volumetric and shape abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. The general objective is to look directly at the long-term neurodevelopmental implications of these neonatal subcortical structures abnormalities. Investigators propose to develop biomarkers of prematurity by comparing the morphological and diffusion properties of subcortical structures between preterm, with and without associated brain injuries, and full-term neonates using brain MRI. By combining subcortical morphological and diffusion properties, investigators hypothesize to be able to: (1) delineate specific correlative relationships between structures regionally and differentially affected by normal maturation and different patterns of white matter injury, and (2) improve the specificity of neuroimaging to predict neurodevelopmental outcomes earlier. The specific aims and general methodology are: 1) Build a new toolbox for neonatal subcortical structures analyses that combine a group lasso-based analysis of significant regions of shape changes, a structural correlation network analysis, a neonatal tractography, and tensor-based analysis on tracts; 2) Ascertain biomarkers of prematurity in neonates with different patterns of abnormalities using correlational and connectivity analysis within and between structures features; 3) Assess the predictive potential of subcortical imaging on neurodevelopmental outcomes by correlating neonatal imaging results with long-term neurodevelopmental scores at 9 and 18 months, and 6-8 years, follow-up. In each of these aims, investigators will use advanced neuroimaging analysis developed by their group and collaborator, including multivariate tensor-based morphometry and multivariate tract-based analysis. This application will provide the first complete subcortical network analysis in both term and preterm neonates. In the first study of its kind for prematurity, investigators will use sparse and multi-task learning to determine which of the biomarkers of prematurity at birth are the best predictors of long-term outcome. Once implemented, these methods will be available to compare subcortical structures for other pathologies in newborns and children.
Read the detailed description
The last months of pregnancy are particularly important for the development of the child's brain, and the consequences of premature birth on its development can be substantial. Prematurely born children are at higher risk of various cognitive impairments and exhibits more behavioral disorders than full-term born children. Thus early detection and management of at risk children are essential. There is growing evidence of significant volumetric abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. Understanding these abnormalities could help elucidate the underlying pathophysiology and enable early determination of at-risk patients, both of which would inform the design of novel treatment strategies. However, to date there is still a lack of sensitive, reliable, and accessible algorithms capable of characterizing the influence of prematurity on the anatomy of neonatal brain subcortical structures. In addition, few studies have looked directly at the long-term neurodevelopmental implications of these neonatal subcortical structures abnormalities. Predicting long-term neurodevelopmental outcomes early on - and preferably at neonatal ages - is likely to have a transformative effect on their outcome. Our preliminary data indicate significant morphological differences in the putamen, ventricles, corpus callosum, and thalamus between preterm and term neonates. Investigators propose to develop biomarkers of prematurity by statistically comparing the morphological and diffusion properties of subcortical structures between preterm and term neonates using brain MRI. These results will further be used in a sparse learning framework to predict long-term neurodevelopmental outcomes of prematurity. Hypotheses: By combining subcortical morphological and diffusion properties, we will be able to: (1) delineate specific correlative relationships between structures regionally and differentially affected by normal maturation and different patterns of white matter injury, and (2) improve the specificity of neuroimaging to predict neurodevelopmental outcomes earlier. Aim 1: Build a new toolbox for neonatal subcortical structures analyses that combine 1) a group lasso-based analysis of significant regions of shape changes, 2) a structural correlation network analysis, 3) a neonatal tractography, and 4) tensor-based analysis on tracts. Aim 2: Ascertain biomarkers of prematurity in neonates with different patterns of abnormalities. Aim 3: Assess the predictive potential of imaging and clinical features on neurodevelopmental outcomes among premature children at 9 and 18 months and 6-8 years of age. Impact: This application will provide the first complete subcortical network analysis in both term and preterm neonates. In the first study of its kind for prematurity, investigators will use sparse and multi-task learning to determine which of the biomarkers of prematurity at birth are the best predictors of long-term outcome. The expected findings could improve the ability to predict these outcomes and enable the design of early treatments - before years of pathological brain development and symptoms occur.
- Conditions
- Premature Birth, Neurodevelopmental Disorders, Brain Development Abnormality, Brain Lesion
- Being tested
- MRI, Neurodevelopmental/Neuropsychological Assessment
- Keywords
- Prematurity, Neuroimaging
- Medical subject headings
- Premature Birth, Neurodevelopmental Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRIDiagnostic test
MRI analysis
Neurodevelopmental/Neuropsychological AssessmentDiagnostic test
Standardized Cognitive and Developmental Tests
| Study group | Role | What they receive |
|---|---|---|
| Infant Control Group | The control arm (term born Infants) will receive an MRI at neonatal age and neurodevelopmental follow-up assessments, investigators will then compare significant morphological and diffusion properties within the brain to those of a Preterm brain. Receives: Diagnostic Test: MRI; Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment | |
| Infant Preterm Group | The experimental group will consist of preterm infants, who will receive an MRI at neonatal age and neurodevelopmental assessments. This groups scans will then be compared to those of the control arm. Significant biomarkers will then be identified. Receives: Diagnostic Test: MRI; Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment | |
| Childhood Control Group | The experimental group will consist of preterm born children aged 6-8 years, who received an MRI at neonatal age and will be called back for a neuropsychological assessment. This groups scans will then be compared to those of the children control arm. Significant biomarkers will then be identified. Receives: Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment | |
| Childhood Preterm Group | The experimental group will consist of term born children aged 6-8 years, who received an MRI at neonatal age and will be called back for a neuropsychological assessment. This groups scans will then be compared to those of the children preterm group. Significant biomarkers will then be identified. Receives: Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Surface Area and Thickness of Subcortical Structures
Measured in Voxel Size (mm)
Measured: 2018 - 2022
Changes in Diffusion values of white matter Tracts
Measured in mm squared per second
Measured: 2018 - 2022
Differences in developmental Quotient / Neuropsychological scores
Measured using standardized tests (Bayley-III and NIH toolbox)
Measured: 2018 - 2022
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2018
- Study start1 Mar 2018
- Primary completion1 Aug 2025 (estimated)
- Study completion1 Aug 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Premature BirthStudies of the same condition, open and under way.
- More trials run by Children's Hospital Los AngelesThe 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
- Cross-sectional
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh, Arizona State University
- Responsible party
- Principal investigator, Natasha Lepore, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03410810
- Sponsor's protocol ID
- CHLA-17-00323
- Status last verified
- Apr 2024
- First submitted
- 19 Jan 2018
- Last updated
- 10 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Paquette N, Shi J, Wang Y, Lao Y, Ceschin R, Nelson MD, Panigrahy A, Lepore N. Ventricular shape and relative position abnormalities in preterm neonates. Neuroimage Clin. 2017 May 28;15:483-493. doi: 10.1016/j.nicl.2017.05.025. eCollection 2017.
PubMed 28649491Lao Y, Wang Y, Shi J, Ceschin R, Nelson MD, Panigrahy A, Lepore N. Thalamic alterations in preterm neonates and their relation to ventral striatum disturbances revealed by a combined shape and pose analysis. Brain Struct Funct. 2016 Jan;221(1):487-506. doi: 10.1007/s00429-014-0921-7. Epub 2014 Nov 1.
PubMed 25366970
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting the Early Childhood Outcomes of Preterm Brain Shape Abnormalities
- ClinicalTrials.gov ID
- NCT03410810
- Acronym / sponsor ID
- CHLA-17-00323
- Conditions
- Premature Birth, Neurodevelopmental Disorders, Brain Development Abnormality, Brain Lesion
- Keywords
- Prematurity, Neuroimaging
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Children's Hospital Los AngelesUniversity, hospital or other
- Collaborators
- University of Pittsburgh, Arizona State University
- Study start
- 1 Mar 2018 (actual)
- Primary completion
- 1 Aug 2025 (estimated)
- Study completion
- 1 Aug 2025 (estimated)
- First posted
- 25 Jan 2018 (actual)
- 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.
Prematurely born children are at higher risk of cognitive impairments and behavioral disorders than full-term children. There is growing evidence of significant volumetric and shape abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. The general objective is to look directly at the long-term neurodevelopmental implications of these neonatal subcortical structures abnormalities. Investigators propose to develop biomarkers of prematurity by comparing the morphological and diffusion properties of subcortical structures between preterm, with and without associated brain injuries, and full-term neonates using brain MRI. By combining subcortical morphological and diffusion properties, investigators hypothesize to be able to: (1) delineate specific correlative relationships between structures regionally and differentially affected by normal maturation and different patterns of white matter injury, and (2) improve the specificity of neuroimaging to predict neurodevelopmental outcomes earlier. The specific aims and general methodology are: 1) Build a new toolbox for neonatal subcortical structures analyses that combine a group lasso-based analysis of significant regions of shape changes, a structural correlation network analysis, a neonatal tractography, and tensor-based analysis on tracts; 2) Ascertain biomarkers of prematurity in neonates with different patterns of abnormalities using correlational and connectivity analysis within and between structures features; 3) Assess the predictive potential of subcortical imaging on neurodevelopmental outcomes by correlating neonatal imaging results with long-term neurodevelopmental scores at 9 and 18 months, and 6-8 years, follow-up. In each of these aims, investigators will use advanced neuroimaging analysis developed by their group and collaborator, including multivariate tensor-based morphometry and multivariate tract-based analysis. This application will provide the first complete subcortical network analysis in both term and preterm neonates. In the first study of its kind for prematurity, investigators will use sparse and multi-task learning to determine which of the biomarkers of prematurity at birth are the best predictors of long-term outcome. Once implemented, these methods will be available to compare subcortical structures for other pathologies in newborns and children.
Detailed description
The last months of pregnancy are particularly important for the development of the child's brain, and the consequences of premature birth on its development can be substantial. Prematurely born children are at higher risk of various cognitive impairments and exhibits more behavioral disorders than full-term born children. Thus early detection and management of at risk children are essential. There is growing evidence of significant volumetric abnormalities in subcortical structures of premature neonates, which may be associated to negative long-term neurodevelopmental outcomes. Understanding these abnormalities could help elucidate the underlying pathophysiology and enable early determination of at-risk patients, both of which would inform the design of novel treatment strategies. However, to date there is still a lack of sensitive, reliable, and accessible algorithms capable of characterizing the influence of prematurity on the anatomy of neonatal brain subcortical structures. In addition, few studies have looked directly at the long-term neurodevelopmental implications of these neonatal subcortical structures abnormalities. Predicting long-term neurodevelopmental outcomes early on - and preferably at neonatal ages - is likely to have a transformative effect on their outcome. Our preliminary data indicate significant morphological differences in the putamen, ventricles, corpus callosum, and thalamus between preterm and term neonates. Investigators propose to develop biomarkers of prematurity by statistically comparing the morphological and diffusion properties of subcortical structures between preterm and term neonates using brain MRI. These results will further be used in a sparse learning framework to predict long-term neurodevelopmental outcomes of prematurity. Hypotheses: By combining subcortical morphological and diffusion properties, we will be able to: (1) delineate specific correlative relationships between structures regionally and differentially affected by normal maturation and different patterns of white matter injury, and (2) improve the specificity of neuroimaging to predict neurodevelopmental outcomes earlier. Aim 1: Build a new toolbox for neonatal subcortical structures analyses that combine 1) a group lasso-based analysis of significant regions of shape changes, 2) a structural correlation network analysis, 3) a neonatal tractography, and 4) tensor-based analysis on tracts. Aim 2: Ascertain biomarkers of prematurity in neonates with different patterns of abnormalities. Aim 3: Assess the predictive potential of imaging and clinical features on neurodevelopmental outcomes among premature children at 9 and 18 months and 6-8 years of age. Impact: This application will provide the first complete subcortical network analysis in both term and preterm neonates. In the first study of its kind for prematurity, investigators will use sparse and multi-task learning to determine which of the biomarkers of prematurity at birth are the best predictors of long-term outcome. The expected findings could improve the ability to predict these outcomes and enable the design of early treatments - before years of pathological brain development and symptoms occur.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Infant Control Group | – | Diagnostic Test: MRI, Diagnostic Test: Neurodevelopmental/Neuropsychological AssessmentThe control arm (term born Infants) will receive an MRI at neonatal age and neurodevelopmental follow-up assessments, investigators will then compare significant morphological and diffusion properties within the brain to those of a Preterm brain. |
| Infant Preterm Group | – | Diagnostic Test: MRI, Diagnostic Test: Neurodevelopmental/Neuropsychological AssessmentThe experimental group will consist of preterm infants, who will receive an MRI at neonatal age and neurodevelopmental assessments. This groups scans will then be compared to those of the control arm. Significant biomarkers will then be identified. |
| Childhood Control Group | – | Diagnostic Test: Neurodevelopmental/Neuropsychological AssessmentThe experimental group will consist of preterm born children aged 6-8 years, who received an MRI at neonatal age and will be called back for a neuropsychological assessment. This groups scans will then be compared to those of the children control arm. Significant biomarkers will then be identified. |
| Childhood Preterm Group | – | Diagnostic Test: Neurodevelopmental/Neuropsychological AssessmentThe experimental group will consist of term born children aged 6-8 years, who received an MRI at neonatal age and will be called back for a neuropsychological assessment. This groups scans will then be compared to those of the children preterm group. Significant biomarkers will then be identified. |
Who may qualify
- Ages
- Up to 8 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Our MRI data will consist of two separate neonatal cohorts. Cohort 1 is an existing dataset of neonates scanned in Pittsburgh as part of a separate completed grant. This cohort was scanned at neonatal equivalent age and will be brought back for childhood neurodevelopmental outcomes at 6-8 years of age. Cohort 2 will be a new prospectively recruited cohort that will be scanned in Los Angeles as part of this proposal and will be brought back for infant neurodevelopmental outcome at 9 and 18 months.
Key inclusion criteria (3 listed)
- Preterm birth (Gestational Age 21-36 weeks)
- English or Spanish speaking families
- PVL and Grade I and II IVH will be considered
Key exclusion criteria (6 listed)
- Shunt
- Intubation, Cpap, Nasal Ventilation
- Chromosomal/Genetic abnormalities
- Mitochondrial/Metabolic Diseases
- Treatment for extracorporeal membrane oxygenation (ECMO)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRIMRI analysis | Diagnostic test | Infant Control Group, Infant Preterm Group |
| Neurodevelopmental/Neuropsychological AssessmentStandardized Cognitive and Developmental Tests | Diagnostic test | Childhood Control Group, Childhood Preterm Group, Infant Control Group, Infant Preterm Group |
Primary outcome
Changes in Surface Area and Thickness of Subcortical Structures
Time frame: 2018 - 2022
Measured in Voxel Size (mm)
Changes in Diffusion values of white matter Tracts
Time frame: 2018 - 2022
Measured in mm squared per second
Differences in developmental Quotient / Neuropsychological scores
Time frame: 2018 - 2022
Measured using standardized tests (Bayley-III and NIH toolbox)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Apr 2024.
- Background: PubMed 28649491Paquette N, Shi J, Wang Y, Lao Y, Ceschin R, Nelson MD, Panigrahy A, Lepore N. Ventricular shape and relative position abnormalities in preterm neonates. Neuroimage Clin. 2017 May 28;15:483-493. doi: 10.1016/j.nicl.2017.05.025. eCollection 2017.
- Background: PubMed 25366970Lao Y, Wang Y, Shi J, Ceschin R, Nelson MD, Panigrahy A, Lepore N. Thalamic alterations in preterm neonates and their relation to ventral striatum disturbances revealed by a combined shape and pose analysis. Brain Struct Funct. 2016 Jan;221(1):487-506. doi: 10.1007/s00429-014-0921-7. Epub 2014 Nov 1.
- Computational Imaging of Brain Organization Research Group (CIBORG) laboratory specializes in mathematical and numerical methods to study brain anatomy and function though magnetic resonance imaging.Link provided by the sponsor.
- 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.
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 Premature Birth and Neurodevelopmental Disorders, run by Children's Hospital Los Angeles 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 3 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 10 Apr 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Natasha Lepore, Phd ((323) 361-5088, nlepore@chla.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Surface Area and Thickness of Subcortical Structures (time frame: 2018 - 2022). The study lists 3 primary outcomes in all. 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 NCT03410810, 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 10 Apr 2024.