An observational study in Myelomeningocele, Brain Malformation and Chiari Malformation Type 2, sponsored by University College, London. Not yet recruiting. Open to participants aged Up to 1 Year. Per ClinicalTrials.gov, last updated 2024-08-21.
Sponsored by University College, London · Observational
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.
Study Population and Methodology
This prospective case-control study will involve the collection of CSF samples from several groups, including:
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-ICH/GOSH, particularly those investigating the neurodevelopmental consequences of spina bifida and related congenital conditions.
58 studies on the registry are indexed under Meningomyelocele; 14 are open to participants now.
This study's planned enrollment of 18 is below the median of 30 across 17 observational studies indexed under Meningomyelocele.
Browse Meningomyelocele studies →University College, London is the lead sponsor of 651 studies on the registry; 149 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 2 (33%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Newborns with Spina Bifida (Postnatal Closure)
Control Group 1 (Newborns with Hydrocephalus)
Control Group 2 (Infants with Spinal Conditions Unrelated to Spina Bifida)
Control Fetal Samples
Mouse Models
Control Mouse Models
Exclusion Criteria:
Newborns with Spina Bifida (Postnatal Closure)
Control Group 1 (Newborns with Hydrocephalus)
Control Group 2 (Infants with Spinal Conditions Unrelated to Spina Bifida)
Fetuses with Spina Bifida (Prenatal Closure)
Control Fetal Samples
Mouse Models
Control Mouse Models
● Mice with any genetic modifications or health conditions that could influence the study's outcomes.
CSF will be collected during postnatal surgical repair at Great Ormond Street Hospital (GOSH)
Other: collection of cerebrospinal fluid
CSF will be collected during suregry at GOSH
Other: collection of cerebrospinal fluid
CSF will be collected during surgery at GOSH.
Other: collection of cerebrospinal fluid
CSF will be collected during prenatal surgery at University College London Hospitals (UCLH).
Other: collection of cerebrospinal fluid
CSF will be collected from fetuses provided by the Human Developmental Biology Resource (HDBR).
Other: collection of cerebrospinal fluid
CSF will be collected
Other: collection of cerebrospinal fluid
CSF will be collected
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
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 year
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 year
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 year
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 year
No study locations are listed for this record.
Plan to share: No — Becuase the infromation provided comes from susceptible (children) population, information won't be shared
Start is estimated for Sep 2024; primary completion for Sep 2025, 12 months later.
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This study is not yet recruiting, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.
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