MyelomeningoceleNCT06560788
The Role of CSF in Chiari II Brain Malformation
An observational study of Myelomeningocele and Brain Malformation, run by University College, London.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 1 year
- Conditions the study is for
- Myelomeningocele, Brain Malformation, Chiari Malformation Type 2
- What is being tested?
- collection of cerebrospinal fluid
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2024to 1 Aug 2027
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 1 year
- All sexes
- Child
Study 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
Who may be able to join
- 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.
Show all 25Show fewer
- 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)
Who cannot join
- 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
Show all 32Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Chiari II Brain Malformation: The Role of Cerebrospinal Fluid in Neurodevelopmental Defects Associated With Spina Bifida
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.
Read the detailed description
Study Population and Methodology
This prospective case-control study will involve the collection of CSF samples from several groups, including:
- Newborns with open spina bifida undergoing postnatal surgery.
- Fetuses undergoing prenatal surgery for spina bifida.
- Newborns with hydrocephalus undergoing shunt surgery (control group).
- Infants undergoing spinal surgery for conditions unrelated to spina bifida (control group).
- Age-matched fetuses obtained from the Human Developmental Biology Resource (HDBR) as controls.
- 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-ICH/GOSH, particularly those investigating the neurodevelopmental consequences of spina bifida and related congenital conditions.
- Being tested
- collection of cerebrospinal fluid
- Keywords
- myelomeningocele, Chiari type 2, brain malformations, cognitive impairment, cerebrospinal fluid
- Medical subject headings
- Meningomyelocele, Arnold-Chiari Malformation, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
collection of cerebrospinal fluidOther
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
| Study group | Role | What they receive |
|---|---|---|
| Case group 1: Children with Open Spina Bifida and Chiari II Malformation | CSF will be collected during postnatal surgical repair at Great Ormond Street Hospital (GOSH) Receives: Other: collection of cerebrospinal fluid | |
| Control group 1: Newborns with hydrocephalus undergoing shunt surgery, unrelated to spina bifida | CSF will be collected during suregry at GOSH Receives: Other: collection of cerebrospinal fluid | |
| Control group 1bis: Infants undergoing spinal surgery for conditions other than SB | CSF will be collected during surgery at GOSH. Receives: Other: collection of cerebrospinal fluid | |
| Case group 2: Fetuses Undergoing Prenatal Surgery for Spina Bifida | CSF will be collected during prenatal surgery at University College London Hospitals (UCLH). Receives: Other: collection of cerebrospinal fluid | |
| Control group 2: Aborted fetuses within the gestational age range of 22-24 weeks, | CSF will be collected from fetuses provided by the Human Developmental Biology Resource (HDBR). Receives: Other: collection of cerebrospinal fluid | |
| Case group 3: mouse model of spina bifida (Cdx2Cre x Pax3flox) | CSF will be collected Receives: Other: collection of cerebrospinal fluid | |
| Control group 3: normal (wild-type) mice | CSF will be collected Receives: Other: collection of cerebrospinal fluid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 1 year
Secondary outcomes (2)
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).
Measured: 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).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2024
- Study start1 Sep 2024 (estimated)
- Primary completion1 Sep 2025 (estimated)
- Study completion1 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for MyelomeningoceleStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 18 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust, University College London Hospitals
- Responsible party
- Principal investigator, Amparo Saenz, University College, London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06560788
- Sponsor's protocol ID
- 23DD12
- Other IDs
- 344434, Z6364106/2024/08/97
- Status last verified
- Aug 2024
- First submitted
- 12 Aug 2024
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Becuase the infromation provided comes from susceptible (children) population, information won't be shared
Publications
Masse O, Kraft E, Ahmad E, Rollins CK, Velasco-Annis C, Yang E, Warfield SK, Shamshirsaz AA, Gholipour A, Feldman HA, Estroff J, Grant PE, Vasung L. Abnormal prenatal brain development in Chiari II malformation. Front Neuroanat. 2023 Apr 17;17:1116948. doi: 10.3389/fnana.2023.1116948. eCollection 2023.
PubMed 37139180Schneider J, Mohr N, Aliatakis N, Seidel U, John R, Promnitz G, Spors B, Kaindl AM. Brain malformations and cognitive performance in spina bifida. Dev Med Child Neurol. 2021 Mar;63(3):295-302. doi: 10.1111/dmcn.14717. Epub 2020 Nov 2.
PubMed 33140418Paslaru FG, Panaitescu AM, Iancu G, Veduta A, Gica N, Paslaru AC, Gheorghiu A, Peltecu G, Gorgan RM. Myelomeningocele Surgery over the 10 Years Following the MOMS Trial: A Systematic Review of Outcomes in Prenatal versus Postnatal Surgical Repair. Medicina (Kaunas). 2021 Jul 12;57(7):707. doi: 10.3390/medicina57070707.
PubMed 34356988Treble-Barna A, Juranek J, Stuebing KK, Cirino PT, Dennis M, Fletcher JM. Prospective and episodic memory in relation to hippocampal volume in adults with spina bifida myelomeningocele. Neuropsychology. 2015 Jan;29(1):92-101. doi: 10.1037/neu0000111. Epub 2014 Jul 28.
PubMed 25068670Treble A, Juranek J, Stuebing KK, Dennis M, Fletcher JM. Functional significance of atypical cortical organization in spina bifida myelomeningocele: relations of cortical thickness and gyrification with IQ and fine motor dexterity. Cereb Cortex. 2013 Oct;23(10):2357-69. doi: 10.1093/cercor/bhs226. Epub 2012 Aug 8.
PubMed 22875857Taylor HB, Barnes MA, Landry SH, Swank P, Fletcher JM, Huang F. Motor contingency learning and infants with Spina Bifida. J Int Neuropsychol Soc. 2013 Feb;19(2):206-15. doi: 10.1017/S1355617712001233. Epub 2013 Jan 8.
PubMed 23298791David AL. Improving motor function in fetal surgery for open spina bifida. BJOG. 2024 May;131(6):768. doi: 10.1111/1471-0528.17730. Epub 2023 Nov 30. No abstract available.
PubMed 38037518Vergote S, Van der Stock J, Kunpalin Y, Bredaki E, Maes H, Banh S, De Catte L, Devlieger R, Lewi L, Devroe S, Spencer R, David A, De Vloo P, Van Calenbergh F, Deprest JA. Patient empowerment improves follow-up data collection after fetal surgery for spina bifida: institutional audit. Ultrasound Obstet Gynecol. 2023 Oct;62(4):565-572. doi: 10.1002/uog.26230. Epub 2023 Aug 27.
PubMed 37099513Bueno D, Parvas M, Nabiuni M, Miyan J. Embryonic cerebrospinal fluid formation and regulation. Semin Cell Dev Biol. 2020 Jun;102:3-12. doi: 10.1016/j.semcdb.2019.09.006. Epub 2019 Oct 12.
PubMed 31615690Zappaterra MD, Lisgo SN, Lindsay S, Gygi SP, Walsh CA, Ballif BA. A comparative proteomic analysis of human and rat embryonic cerebrospinal fluid. J Proteome Res. 2007 Sep;6(9):3537-48. doi: 10.1021/pr070247w. Epub 2007 Aug 16.
PubMed 17696520Pal K, Sharma U, Gupta DK, Pratap A, Jagannathan NR. Metabolite profile of cerebrospinal fluid in patients with spina bifida: a proton magnetic resonance spectroscopy study. Spine (Phila Pa 1976). 2005 Feb 1;30(3):E68-72. doi: 10.1097/01.brs.0000152161.08313.04.
PubMed 15681999Shokohi R, Nabiuni M, Irian S, Miyan JA. In Vitro Effects of Wistar Rat Prenatal and Postnatal Cerebrospinal Fluid on Neural Differentiation and P roliferation of Mesenchymal Stromal Cells Derived from Bone Marrow. Cell J. 2018 Jan;19(4):537-544. doi: 10.22074/cellj.2018.4130. Epub 2017 Nov 4.
PubMed 29105387Alonso MI, Lamus F, Carnicero E, Moro JA, de la Mano A, Fernandez JMF, Desmond ME, Gato A. Embryonic Cerebrospinal Fluid Increases Neurogenic Activity in the Brain Ventricular-Subventricular Zone of Adult Mice. Front Neuroanat. 2017 Dec 19;11:124. doi: 10.3389/fnana.2017.00124. eCollection 2017.
PubMed 29311854Eid L, Lachance M, Hickson G, Rossignol E. Ex Utero Electroporation and Organotypic Slice Cultures of Embryonic Mouse Brains for Live-Imaging of Migrating GABAergic Interneurons. J Vis Exp. 2018 Apr 20;(134):57526. doi: 10.3791/57526.
PubMed 29733310
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chiari II Brain Malformation: The Role of Cerebrospinal Fluid in Neurodevelopmental Defects Associated With Spina Bifida
- ClinicalTrials.gov ID
- NCT06560788
- Acronym / sponsor ID
- 23DD12
- Keywords
- myelomeningocele, Chiari type 2, brain malformations, cognitive impairment, cerebrospinal fluid
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- Great Ormond Street Hospital for Children NHS Foundation Trust, University College London Hospitals
- Study start
- 1 Sep 2024 (estimated)
- Primary completion
- 1 Sep 2025 (estimated)
- Study completion
- 1 Aug 2027 (estimated)
- First posted
- 19 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Population and Methodology
This prospective case-control study will involve the collection of CSF samples from several groups, including:
- Newborns with open spina bifida undergoing postnatal surgery.
- Fetuses undergoing prenatal surgery for spina bifida.
- Newborns with hydrocephalus undergoing shunt surgery (control group).
- Infants undergoing spinal surgery for conditions unrelated to spina bifida (control group).
- Age-matched fetuses obtained from the Human Developmental Biology Resource (HDBR) as controls.
- 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-ICH/GOSH, particularly those investigating the neurodevelopmental consequences of spina bifida and related congenital conditions.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Target follow-up
- 1 Day
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| Case group 1: Children with Open Spina Bifida and Chiari II Malformation | – | Other: collection of cerebrospinal fluidCSF will be collected during postnatal surgical repair at Great Ormond Street Hospital (GOSH) |
| Control group 1: Newborns with hydrocephalus undergoing shunt surgery, unrelated to spina bifida | – | Other: collection of cerebrospinal fluidCSF will be collected during suregry at GOSH |
| Control group 1bis: Infants undergoing spinal surgery for conditions other than SB | – | Other: collection of cerebrospinal fluidCSF will be collected during surgery at GOSH. |
| Case group 2: Fetuses Undergoing Prenatal Surgery for Spina Bifida | – | Other: collection of cerebrospinal fluidCSF will be collected during prenatal surgery at University College London Hospitals (UCLH). |
| Control group 2: Aborted fetuses within the gestational age range of 22-24 weeks, | – | Other: collection of cerebrospinal fluidCSF will be collected from fetuses provided by the Human Developmental Biology Resource (HDBR). |
| Case group 3: mouse model of spina bifida (Cdx2Cre x Pax3flox) | – | Other: collection of cerebrospinal fluidCSF will be collected |
| Control group 3: normal (wild-type) mice | – | Other: collection of cerebrospinal fluidCSF will be collected |
Who may qualify
- Ages
- Up to 1 year
- Sex
- All
- Age groups
- Child
- Study 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
Key inclusion criteria (25 listed)
- 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)
Key exclusion criteria (32 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| collection of cerebrospinal fluidCSF 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 | Other | Case group 1: Children with Open Spina Bifida and Chiari II Malformation, Case group 2: Fetuses Undergoing Prenatal Surgery for Spina Bifida, Case group 3: mouse model of spina bifida (Cdx2Cre x Pax3flox), Control group 1: Newborns with hydrocephalus undergoing shunt surgery, unrelated to spina bifida, Control group 1bis: Infants undergoing spinal surgery for conditions other than SB, Control group 2: Aborted fetuses within the gestational age range of 22-24 weeks,, Control group 3: normal (wild-type) mice |
Primary outcome
Identification of Proteins in Cerebrospinal Fluid (CSF)
Time frame: 1 year
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.
Quantification of Protein Concentrations in Cerebrospinal Fluid (CSF)
Time frame: 1 year
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.
2 secondary outcomes
Measurement of Neurogenesis in Median Ganglionic Eminence (MGE) Cultures
Time frame: 1 year
Measurement of Neuronal Migration in Median Ganglionic Eminence (MGE) Cultures
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Results publication: PubMed 37139180Masse O, Kraft E, Ahmad E, Rollins CK, Velasco-Annis C, Yang E, Warfield SK, Shamshirsaz AA, Gholipour A, Feldman HA, Estroff J, Grant PE, Vasung L. Abnormal prenatal brain development in Chiari II malformation. Front Neuroanat. 2023 Apr 17;17:1116948. doi: 10.3389/fnana.2023.1116948. eCollection 2023.
- Results publication: PubMed 33140418Schneider J, Mohr N, Aliatakis N, Seidel U, John R, Promnitz G, Spors B, Kaindl AM. Brain malformations and cognitive performance in spina bifida. Dev Med Child Neurol. 2021 Mar;63(3):295-302. doi: 10.1111/dmcn.14717. Epub 2020 Nov 2.
- Results publication: PubMed 34356988Paslaru FG, Panaitescu AM, Iancu G, Veduta A, Gica N, Paslaru AC, Gheorghiu A, Peltecu G, Gorgan RM. Myelomeningocele Surgery over the 10 Years Following the MOMS Trial: A Systematic Review of Outcomes in Prenatal versus Postnatal Surgical Repair. Medicina (Kaunas). 2021 Jul 12;57(7):707. doi: 10.3390/medicina57070707.
- Results publication: PubMed 25068670Treble-Barna A, Juranek J, Stuebing KK, Cirino PT, Dennis M, Fletcher JM. Prospective and episodic memory in relation to hippocampal volume in adults with spina bifida myelomeningocele. Neuropsychology. 2015 Jan;29(1):92-101. doi: 10.1037/neu0000111. Epub 2014 Jul 28.
- Results publication: PubMed 22875857Treble A, Juranek J, Stuebing KK, Dennis M, Fletcher JM. Functional significance of atypical cortical organization in spina bifida myelomeningocele: relations of cortical thickness and gyrification with IQ and fine motor dexterity. Cereb Cortex. 2013 Oct;23(10):2357-69. doi: 10.1093/cercor/bhs226. Epub 2012 Aug 8.
- Results publication: PubMed 23298791Taylor HB, Barnes MA, Landry SH, Swank P, Fletcher JM, Huang F. Motor contingency learning and infants with Spina Bifida. J Int Neuropsychol Soc. 2013 Feb;19(2):206-15. doi: 10.1017/S1355617712001233. Epub 2013 Jan 8.
- Results publication: PubMed 38037518David AL. Improving motor function in fetal surgery for open spina bifida. BJOG. 2024 May;131(6):768. doi: 10.1111/1471-0528.17730. Epub 2023 Nov 30. No abstract available.
- Results publication: PubMed 37099513Vergote S, Van der Stock J, Kunpalin Y, Bredaki E, Maes H, Banh S, De Catte L, Devlieger R, Lewi L, Devroe S, Spencer R, David A, De Vloo P, Van Calenbergh F, Deprest JA. Patient empowerment improves follow-up data collection after fetal surgery for spina bifida: institutional audit. Ultrasound Obstet Gynecol. 2023 Oct;62(4):565-572. doi: 10.1002/uog.26230. Epub 2023 Aug 27.
- Results publication: PubMed 31615690Bueno D, Parvas M, Nabiuni M, Miyan J. Embryonic cerebrospinal fluid formation and regulation. Semin Cell Dev Biol. 2020 Jun;102:3-12. doi: 10.1016/j.semcdb.2019.09.006. Epub 2019 Oct 12.
- Results publication: PubMed 17696520Zappaterra MD, Lisgo SN, Lindsay S, Gygi SP, Walsh CA, Ballif BA. A comparative proteomic analysis of human and rat embryonic cerebrospinal fluid. J Proteome Res. 2007 Sep;6(9):3537-48. doi: 10.1021/pr070247w. Epub 2007 Aug 16.
- Results publication: PubMed 15681999Pal K, Sharma U, Gupta DK, Pratap A, Jagannathan NR. Metabolite profile of cerebrospinal fluid in patients with spina bifida: a proton magnetic resonance spectroscopy study. Spine (Phila Pa 1976). 2005 Feb 1;30(3):E68-72. doi: 10.1097/01.brs.0000152161.08313.04.
- Results publication: PubMed 29105387Shokohi R, Nabiuni M, Irian S, Miyan JA. In Vitro Effects of Wistar Rat Prenatal and Postnatal Cerebrospinal Fluid on Neural Differentiation and P roliferation of Mesenchymal Stromal Cells Derived from Bone Marrow. Cell J. 2018 Jan;19(4):537-544. doi: 10.22074/cellj.2018.4130. Epub 2017 Nov 4.
- Individual participant dataSharing planned: No. Becuase the infromation provided comes from susceptible (children) population, information won't be shared
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
An observational study of Myelomeningocele and Brain Malformation, run by University College, London.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrew Copp, PhD (02079052698, a.copp@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of Proteins in Cerebrospinal Fluid (CSF) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06560788, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.