Ignite Creation Date:
2024-10-26 @ 3:38 PM
Last Modification Date:
2024-10-26 @ 3:38 PM
Study NCT ID:
NCT06560788
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-12
Brief Title:
The Role of CSF in Chiari II Brain Malformation
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Chiari II Brain Malformation The Role of Cerebrospinal Fluid in Neurodevelopmental Defects Associated With Spina Bifida
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Spina bifida particularly its most severe form known as open spina bifida myelomeningocele is a significant congenital disorder that results in profound neurological impairments including Chiari II malformation This malformation is associated with the downward displacement of the cerebellum and brainstem into the spinal canal often leading to hydrocephalus a condition where cerebrospinal fluid CSF accumulates in the brain1 These conditions can result in a range of complications including cognitive and motor disabilities learning difficulties and in severe cases early mortality12
While surgical interventions including prenatal and postnatal surgeries have been developed to manage the physical manifestations of spina bifida and Chiari II malformation these procedures have not been fully successful in addressing the associated brain anomalies3 This study aims to explore the hypothesis that the composition of CSF plays a critical role in the development of these brain defects Specifically it is hypothesized that the rapid replenishment of CSF due to its leakage from the open spine in spina bifida results in a less mature fluid composition which negatively affects neurogenesis and neuronal migration during critical periods of brain development
While surgical interventions including prenatal and postnatal surgeries have been developed to manage the physical manifestations of spina bifida and Chiari II malformation these procedures have not been fully successful in addressing the associated brain anomalies3 This study aims to explore the hypothesis that the composition of CSF plays a critical role in the development of these brain defects Specifically it is hypothesized that the rapid replenishment of CSF due to its leakage from the open spine in spina bifida results in a less mature fluid composition which negatively affects neurogenesis and neuronal migration during critical periods of brain development
Detailed Description:
Study Population and Methodology
This prospective case-control study will involve the collection of CSF samples from several groups including
1 Newborns with open spina bifida undergoing postnatal surgery
2 Fetuses undergoing prenatal surgery for spina bifida
3 Newborns with hydrocephalus undergoing shunt surgery control group
4 Infants undergoing spinal surgery for conditions unrelated to spina bifida control group
5 Age-matched fetuses obtained from the Human Developmental Biology Resource HDBR as controls
6 Mouse models This includes a genetic mouse model of spina bifida Cdx2Cre x Pax3flox and normal wild-type mice as controls
These samples will be analyzed using mass spectrometry-based proteomics to identify differences in protein composition and concentrations between the groups Additionally brain slices from human embryos and mouse models will be cultured in the presence of these CSF samples to assess the impact on neurogenesis and neuronal migration
Expected Benefits The findings from this study are expected to provide new insights into the pathogenesis of Chiari II malformation and other associated brain anomalies in children with spina bifida By understanding how CSF composition influences brain development the study could pave the way for novel therapeutic strategies aimed at modifying CSF composition during early pregnancy This could potentially prevent or mitigate the neurological impairments associated with spina bifida ultimately improving the quality of life for affected individuals
Impact on Clinical Practice and Policy Should the study confirm the hypothesis it could lead to changes in clinical practices concerning the management of spina bifida and Chiari II malformation For instance it might inform the development of new prenatal treatments or interventions designed to normalize CSF composition before significant brain damage occurs4-6 This would represent a significant advancement in fetal surgery and pediatric neurosurgery with the potential to influence guidelines and policies within the NHS and other healthcare systems globally
Relation to Academic Qualification This study is being conducted as part of the Lewis Spitz PhD program at University College London UCL and Great Ormond Street Institute of Child Health GOSH ICH The research builds upon previous studies sponsored by UCL-ICHGOSH particularly those investigating the neurodevelopmental consequences of spina bifida and related congenital conditions
This prospective case-control study will involve the collection of CSF samples from several groups including
1 Newborns with open spina bifida undergoing postnatal surgery
2 Fetuses undergoing prenatal surgery for spina bifida
3 Newborns with hydrocephalus undergoing shunt surgery control group
4 Infants undergoing spinal surgery for conditions unrelated to spina bifida control group
5 Age-matched fetuses obtained from the Human Developmental Biology Resource HDBR as controls
6 Mouse models This includes a genetic mouse model of spina bifida Cdx2Cre x Pax3flox and normal wild-type mice as controls
These samples will be analyzed using mass spectrometry-based proteomics to identify differences in protein composition and concentrations between the groups Additionally brain slices from human embryos and mouse models will be cultured in the presence of these CSF samples to assess the impact on neurogenesis and neuronal migration
Expected Benefits The findings from this study are expected to provide new insights into the pathogenesis of Chiari II malformation and other associated brain anomalies in children with spina bifida By understanding how CSF composition influences brain development the study could pave the way for novel therapeutic strategies aimed at modifying CSF composition during early pregnancy This could potentially prevent or mitigate the neurological impairments associated with spina bifida ultimately improving the quality of life for affected individuals
Impact on Clinical Practice and Policy Should the study confirm the hypothesis it could lead to changes in clinical practices concerning the management of spina bifida and Chiari II malformation For instance it might inform the development of new prenatal treatments or interventions designed to normalize CSF composition before significant brain damage occurs4-6 This would represent a significant advancement in fetal surgery and pediatric neurosurgery with the potential to influence guidelines and policies within the NHS and other healthcare systems globally
Relation to Academic Qualification This study is being conducted as part of the Lewis Spitz PhD program at University College London UCL and Great Ormond Street Institute of Child Health GOSH ICH The research builds upon previous studies sponsored by UCL-ICHGOSH particularly those investigating the neurodevelopmental consequences of spina bifida and related congenital conditions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None