The Role of CSF in Chiari II Brain Malformation
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeUp to 1
SponsorUniversity College, London
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Newborns scheduled for shunt surgery for hydrocephalus unrelated to spina bifida.
Disqualifiers
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
Trial population
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
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
collection of cerebrospinal fluid
Other interventionCSF 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
Treatment groups
18 Participants
are divided into 7 treatment groups7
Treatment groupsSee each treatment group below.
Group A: Case group 1: Children with Open Spina Bifida and Chiari II Malformation1 intervention
Group B: Control group 1: Newborns with hydrocephalus undergoing shunt surgery, unrelated to spina bifida1 intervention
Group C: Control group 1bis: Infants undergoing spinal surgery for conditions other than SB1 intervention
Group D: Case group 2: Fetuses Undergoing Prenatal Surgery for Spina Bifida1 intervention
Group E: Control group 2: Aborted fetuses within the gestational age range of 22-24 weeks,1 intervention
Group F: Case group 3: mouse model of spina bifida (Cdx2Cre x Pax3flox)1 intervention
Group G: Control group 3: normal (wild-type) mice1 intervention
Trial outcomes
Primary outcomes
1
Identification of Proteins in Cerebrospinal Fluid (CSF)
The presence of specific proteins in cerebrospinal fluid (CSF) will be identified through proteomic analysis. This outcome will focus on categorizing which proteins are present in the CSF samples from patients with spina bifida and control participants.
Time frame
1 year2
Quantification of Protein Concentrations in Cerebrospinal Fluid (CSF)
The concentration of each identified protein in cerebrospinal fluid (CSF) will be measured using proteomic analysis. This outcome will report the amount of each protein present in the CSF, expressed in micrograms per milliliter (µg/mL) or nanograms per milliliter (ng/mL), allowing for comparison between patients with spina bifida and controls.
Time frame
1 yearSecondary outcomes
1
Measurement of Neurogenesis in Median Ganglionic Eminence (MGE) Cultures
The rate of neurogenesis in the median ganglionic eminence (MGE) of embryonic brain slice cultures will be measured following exposure to cerebrospinal fluid (CSF) from patients with Chiari II malformation and control subjects. The outcome will focus on the number of proliferating neurons per unit area, measured in cells per square millimeter (cells/mm²).
Time frame
1 year2
Measurement of Neuronal Migration in Median Ganglionic Eminence (MGE) Cultures
The distance of neuronal migration in the median ganglionic eminence (MGE) of embryonic brain slice cultures will be measured following exposure to cerebrospinal fluid (CSF) from patients with Chiari II malformation and control subjects. The outcome will report the migration distance of neurons, measured in micrometers (µm).
Time frame
1 yearLocations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University College, London
Lead sponsor
Great Ormond Street Hospital for Children NHS Foundation Trust
Collaborator
University College London Hospitals
Collaborator
Source ClinicalTrials.gov
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