We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Childhood Outcomes of Preterm Brain Abnormalities

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03410810
Recruitment Status : Recruiting
First Posted : January 25, 2018
Last Update Posted : June 14, 2022
Sponsor:
Collaborators:
University of Pittsburgh
Arizona State University
Information provided by (Responsible Party):
Natasha Lepore, Children's Hospital Los Angeles

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief 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. 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.

Condition or disease Intervention/treatment
Premature Birth Neurodevelopmental Disorders Brain Development Abnormality Brain Lesion Diagnostic Test: MRI Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment

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
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 80 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Predicting the Early Childhood Outcomes of Preterm Brain Shape Abnormalities
Actual Study Start Date : March 1, 2018
Estimated Primary Completion Date : August 1, 2023
Estimated Study Completion Date : August 1, 2023
Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort Intervention/treatment
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.
 Diagnostic Test: MRI
MRI analysis

Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests
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.
 Diagnostic Test: MRI
MRI analysis

Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests
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.
 Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests
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.
 Diagnostic Test: Neurodevelopmental/Neuropsychological Assessment
Standardized Cognitive and Developmental Tests


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Changes in Surface Area and Thickness of Subcortical Structures [ Time Frame: 2018 - 2022 ]
    Measured in Voxel Size (mm)

  2. Changes in Diffusion values of white matter Tracts [ Time Frame: 2018 - 2022 ]
    Measured in mm squared per second

  3. Differences in developmental Quotient / Neuropsychological scores [ Time Frame: 2018 - 2022 ]
    Measured using standardized tests (Bayley-III and NIH toolbox)


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 8 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • Preterm birth (Gestational Age 21-36 weeks)
  • English or Spanish speaking families
  • PVL and Grade I and II IVH will be considered

Exclusion Criteria:

  • Shunt
  • Intubation, Cpap, Nasal Ventilation
  • Chromosomal/Genetic abnormalities
  • Mitochondrial/Metabolic Diseases
  • Treatment for extracorporeal membrane oxygenation (ECMO)
  • Grade III and IV IVH (optional)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03410810


Contacts
Layout table for location contacts
Contact: Natasha Lepore, Phd (323) 361-5088 nlepore@chla.usc.edu
Contact: Natacha Paquette, Phd (323) 361-8726 npaquette@chla.usc.edu

Locations
Layout table for location information
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Emy Dacalos    323-361-7309    edacalos@chla.usc.edu   
Contact: Kayla Guzman, Phd    (323) 361-6876    kayguzman@chla.usc.edu   
Sponsors and Collaborators
Children's Hospital Los Angeles
University of Pittsburgh
Arizona State University
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications:

Layout table for additonal information
Responsible Party: Natasha Lepore, Professor of Research Radiology, Children's Hospital Los Angeles
ClinicalTrials.gov Identifier: NCT03410810    
Other Study ID Numbers: CHLA-17-00323
First Posted: January 25, 2018    Key Record Dates
Last Update Posted: June 14, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Natasha Lepore, Children's Hospital Los Angeles:
Prematurity
Neuroimaging
Additional relevant MeSH terms:
Layout table for MeSH terms
Premature Birth
Congenital Abnormalities
Neurodevelopmental Disorders
Obstetric Labor, Premature
 Obstetric Labor Complications
Pregnancy Complications
Mental Disorders