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NCT06560788

The Role of CSF in Chiari II Brain Malformation

Sponsor: University College, London

View on ClinicalTrials.gov

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 mortality1,2. 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.

Official title: Chiari II Brain Malformation: The Role of Cerebrospinal Fluid in Neurodevelopmental Defects Associated With Spina Bifida

Key Details

Gender

All

Age Range

Any - 1 Year

Study Type

OBSERVATIONAL

Enrollment

Start Date

2024-09-01

Completion Date

2027-08-01

Last Updated

2024-08-21

Healthy Volunteers

Not specified

Conditions

Myelomeningocele Brain Malformation Chiari Malformation Type 2

Interventions

OTHER

collection of cerebrospinal fluid

CSF is collected as part of routine care in any of the surgeries listed in the control or cases groups. We will take part of that CSF for proteomic analysis

Inclusion Criteria: Newborns with Spina Bifida (Postnatal Closure) * Diagnosed with open spina bifida (myelomeningocele). * Scheduled for postnatal surgical closure of the spinal lesion at Great Ormond Street Hospital (GOSH). * Age: Between 1 day to 1 year old. Control Group 1 (Newborns with Hydrocephalus) * Newborns scheduled for shunt surgery for hydrocephalus unrelated to spina bifida. * Age and sex matched to the spina bifida newborns as closely as possible. * Age: Between 1 day to 1 year old. Control Group 2 (Infants with Spinal Conditions Unrelated to Spina Bifida) * Infants undergoing paned spinal surgery for conditions such as spinal lipoma, fatty filum, tethered cord, etc. * Age and sex matched to the spina bifida newborns as closely as possible. * Age: Between 1 day to 1 year old. Fetuses with Spina Bifida (Prenatal Closure) * Prenatal diagnosis of spina bifida (myelomeningocele) and scheduled for fetal surgery at UCLH. * Reviewed by Mr Thompson at his outpatient clinic at GOSH * Gestational age: Between 22 and 24 weeks. Control Fetal Samples * Aborted fetuses within the gestational age range of 22-24 weeks. * Samples obtained through the Human Developmental Biology Resource (HDBR). Mouse Models * Genetic mouse model of spina bifida (Cdx2Cre x Pax3flox). * At embryonic day (E)13.5 (end of the embryonic period) and E18.5 (just before birth) Control Mouse Models * Normal (wild-type) mice to serve as controls. * Normal brain development * At embryonic day (E)13.5 (end of the embryonic period) and E18.5 (just before birth) Exclusion Criteria: Newborns with Spina Bifida (Postnatal Closure) * Newborns who have undergone previous surgical intervention. * Presence of additional unrelated congenital anomalies that could affect cerebrospinal fluid (CSF) composition like meningitis or intraventricular bleeding * Older than 1 year and 1 month of age. * Parents refused to participate * Native language different to English with no translation services available Control Group 1 (Newborns with Hydrocephalus) * Newborns with hydrocephalus caused by spina bifida. * Presence of intraventricular infection or haemorrhage. * Older than 1 year and 1 month of age. * Parents refused to participate * Native language different to English with no translation services available Control Group 2 (Infants with Spinal Conditions Unrelated to Spina Bifida) * Infants who were born with spina bifida * Infants with coexisting conditions that could affect CSF composition like intraspinal tumours, empyema or haemorrhage. * Older than 1 year and 1 month of age. * Parents refused to participate * Native language different to English with no translation services available Fetuses with Spina Bifida (Prenatal Closure) * Fetuses with additional major anomalies unrelated to spina bifida like diaphragmatic hernia. * Gestational age outside the range of 22-24 weeks. * Surgery performed by other neurosurgery team (not GOSH) * Parents refused to participate * Native language different to English with no translation services available Control Fetal Samples * Poorly preserved aborted fetuses not suitable for CSF collection. * Gestational age outside the range 22-24 weeks. Mouse Models * Mice with any genetic modifications other than those specified for the spina bifida model. * Mice with other congenital or acquired anomalies affecting the central nervous system. Control Mouse Models ● Mice with any genetic modifications or health conditions that could influence the study's outcomes.