Fetal AnomalyNCT03544970
An Audit of the Posterior Fossa Characterization in Open Spina Bifida Based on Tertiary Center Experience
An observational study of Fetal Anomaly and Spinal Dysraphism, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Brain stem and posterior fossa measurements in spina bifida aperta fetuses to compare them with normal population. Additionally, Describe the difference between pre- and postoperative findings. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Fetal Anomaly, Spinal Dysraphism, Chiari Malformation Type 2
- How many people
- 316 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Apr 2017to 31 Oct 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Fetuses with spina bifida aperta with an additiona lsubgroup of matched pairs with pre- and postoperative imaging
Who may be able to join
- patients were those having fetal MR examination for additional assessment because of the prenatal diagnosis of SBA on ultrasound.
- appropriate gestational age - matched controls. The latter were fetuses assessed for other congenital anomalies, which do not affect the central nervous system (CNS) or were scanned for suspected CNS abnormalities with normal prenatal US, fetal MR and normal postnatal evaluation
Who cannot join
- twin pregnancy, syndromal pathology, fetal hydrops or anhydramnios.
- poor image quality
Trial locations and contacts
1 site in 1 country.
About this study
Brain stem and posterior fossa measurements in spina bifida aperta fetuses to compare them with normal population. Additionally, Describe the difference between pre- and postoperative findings.
Read the detailed description
Spina bifida aperta (SBA), often referred to as myelomeningocele (MMC) or myeloschisis, is a devastating yet non-lethal congenital malformation with complex physical and neurodevelopmental sequelae. Its prevalence is approximately 4.9 per 10,000 live births in Europe and 3.17 in the United States. SBA results in motor and sensory deficits, their extension being defined by the upper level of the anatomical defect. These range, as the level increases, from bladder, bowel and sexual dysfunction, to involvement of the lower and even upper extremities, and secondary orthopaedic disabilities. Despite improvements in prevention, diagnosis, and postnatal management, SBA remains a major source of morbidity and mortality throughout the world. Children with SBA almost invariably have an associated Chiari II hindbrain malformation (CM II) and ventriculomegaly. The Chiari II malformation is characterized by posterior fossa (PF) and brain stem abnormalities, with downward displacement and compression of the cerebellum and brain stem.
Geerdink demonstrated that morphometric measures reliably quantify the morphological distortions of Chiari II malformation on postnatal MR images. These included downward herniation of the cerebellum, displacement of pons, medulla and fourth ventricle, medullary kinking, abnormal fourth ventricle, tentorium and mesencephalic tectum. The mamillopontine distance (MPD) and the cerebellar width were the most sensitive and specific determinant of Chiari II. Some foetuses with SBA have ventriculomegaly and its degree is believed to be predictive for the need of postnatal shunting.
In 2011, the Management of Myelomeningocele Study (MOMS) demonstrated the benefit of in utero repair of MMC as the need for ventricular shunting at 12 months was reduced and motor outcome at 30 months improved. Fetuses with the suspicion of SBA should be assessed comprehensively to counsel parents about the expected outcome and whether they would be candidates for fetal surgery. In this assessment, fetal MR has a crucial role to characterize the extent of brain abnormalities, the level of the lesion, and to rule out additional anomalies in fetuses with SBA. For fetal surgery eligibility, the presence of CM II on MR is a necessary finding. Many measurements have been proposed to describe the typical PF changes in fetuses with SBA, yet the reproducibility of these has rarely been studied. These include the transverse cerebellar diameter (TCD), the transverse diameter of the posterior fossa (TDPF), the midsagittal PF area, the level of cerebellar herniation and the clivus-supraocciput angle (CSA). These parameters have also been shown to change after in utero repair of SBA in small series and at different time points after fetal surgery, yet no study has consistently reported early postoperative assessment in utero.
The aims of this study were threefold: (1) to assess the reproducibility of measurements of the brain stem and PF that have been suggested to be representative on postnatal 8,9 and prenatal MR imaging (2) apply those parameters that were shown to be reproducible, to discriminate fetuses with SBA from gestational age matched fetuses with a normal PF; (3) and document early changes in these measurements one week after fetal surgery.
- Conditions
- Fetal Anomaly, Spinal Dysraphism, Chiari Malformation Type 2
- Keywords
- fetal MRI, Posterior fossa
- Medical subject headings
- Congenital Abnormalities, Spinal Dysraphism, Arnold-Chiari Malformation
What is being measured
The primary outcome is the main question the study is designed to answer.
(1) assess the reliability of brain stem and posterior fossa measurements and compare the reliable ones with a normal populations (2) and between paired pre- and postsurgical fetuses
Biometric variables include the transverse cerebellar diameter (TCD), Transverse diameter of the fossa posterior (TDPF), the midsagittal PF area. The ventricular width will be measured in the coronal plane according to Garel and in case of asymmetry the largest value will be taken into account. Mammilopontine distande (MPD), the level of kinking of the brain stem, medullary length, tentorial length and width of the cisterna magna will be measured. The width of the foramen magnum is defined as the distance between opisthion to the basion. Tonsillar level (TL) will be measured by drawing a perpendicular line from the foramen magnum to the lowest cerebellar portion. In the presence of cerebellar herniation the deepest portion will be used. The cerebellopontine angle will also be measured.
These are all metric data and will be reported in mm. To adjust for normal changes according to gestational age, there will be a correction based on an observed/expeted ratio for the parameters.
Measured: Examinations from 2011 - 2016
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2018
- Study start1 Apr 2017
- Primary completion26 Oct 2017
- Study completion31 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fetal AnomalyStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe 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
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 316 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03544970
- Sponsor's protocol ID
- s60814
- Status last verified
- Dec 2018
- First submitted
- 17 May 2018
- Last updated
- 19 Dec 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Audit of the Posterior Fossa Characterization in Open Spina Bifida Based on Tertiary Center Experience
- ClinicalTrials.gov ID
- NCT03544970
- Acronym / sponsor ID
- s60814
- Conditions
- Fetal Anomaly, Spinal Dysraphism, Chiari Malformation Type 2
- Keywords
- fetal MRI, Posterior fossa
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 316 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Study start
- 1 Apr 2017 (actual)
- Primary completion
- 26 Oct 2017 (actual)
- Study completion
- 31 Oct 2018 (actual)
- First posted
- 4 Jun 2018 (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.
Brain stem and posterior fossa measurements in spina bifida aperta fetuses to compare them with normal population. Additionally, Describe the difference between pre- and postoperative findings.
Detailed description
Spina bifida aperta (SBA), often referred to as myelomeningocele (MMC) or myeloschisis, is a devastating yet non-lethal congenital malformation with complex physical and neurodevelopmental sequelae. Its prevalence is approximately 4.9 per 10,000 live births in Europe and 3.17 in the United States. SBA results in motor and sensory deficits, their extension being defined by the upper level of the anatomical defect. These range, as the level increases, from bladder, bowel and sexual dysfunction, to involvement of the lower and even upper extremities, and secondary orthopaedic disabilities. Despite improvements in prevention, diagnosis, and postnatal management, SBA remains a major source of morbidity and mortality throughout the world. Children with SBA almost invariably have an associated Chiari II hindbrain malformation (CM II) and ventriculomegaly. The Chiari II malformation is characterized by posterior fossa (PF) and brain stem abnormalities, with downward displacement and compression of the cerebellum and brain stem.
Geerdink demonstrated that morphometric measures reliably quantify the morphological distortions of Chiari II malformation on postnatal MR images. These included downward herniation of the cerebellum, displacement of pons, medulla and fourth ventricle, medullary kinking, abnormal fourth ventricle, tentorium and mesencephalic tectum. The mamillopontine distance (MPD) and the cerebellar width were the most sensitive and specific determinant of Chiari II. Some foetuses with SBA have ventriculomegaly and its degree is believed to be predictive for the need of postnatal shunting.
In 2011, the Management of Myelomeningocele Study (MOMS) demonstrated the benefit of in utero repair of MMC as the need for ventricular shunting at 12 months was reduced and motor outcome at 30 months improved. Fetuses with the suspicion of SBA should be assessed comprehensively to counsel parents about the expected outcome and whether they would be candidates for fetal surgery. In this assessment, fetal MR has a crucial role to characterize the extent of brain abnormalities, the level of the lesion, and to rule out additional anomalies in fetuses with SBA. For fetal surgery eligibility, the presence of CM II on MR is a necessary finding. Many measurements have been proposed to describe the typical PF changes in fetuses with SBA, yet the reproducibility of these has rarely been studied. These include the transverse cerebellar diameter (TCD), the transverse diameter of the posterior fossa (TDPF), the midsagittal PF area, the level of cerebellar herniation and the clivus-supraocciput angle (CSA). These parameters have also been shown to change after in utero repair of SBA in small series and at different time points after fetal surgery, yet no study has consistently reported early postoperative assessment in utero.
The aims of this study were threefold: (1) to assess the reproducibility of measurements of the brain stem and PF that have been suggested to be representative on postnatal 8,9 and prenatal MR imaging (2) apply those parameters that were shown to be reproducible, to discriminate fetuses with SBA from gestational age matched fetuses with a normal PF; (3) and document early changes in these measurements one week after fetal surgery.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Fetuses with spina bifida aperta with an additiona lsubgroup of matched pairs with pre- and postoperative imaging
Key inclusion criteria (2 listed)
- patients were those having fetal MR examination for additional assessment because of the prenatal diagnosis of SBA on ultrasound.
- appropriate gestational age - matched controls. The latter were fetuses assessed for other congenital anomalies, which do not affect the central nervous system (CNS) or were scanned for suspected CNS abnormalities with normal prenatal US, fetal MR and normal postnatal evaluation
Key exclusion criteria (2 listed)
- twin pregnancy, syndromal pathology, fetal hydrops or anhydramnios.
- poor image quality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
(1) assess the reliability of brain stem and posterior fossa measurements and compare the reliable ones with a normal populations (2) and between paired pre- and postsurgical fetuses
Time frame: Examinations from 2011 - 2016
Biometric variables include the transverse cerebellar diameter (TCD), Transverse diameter of the fossa posterior (TDPF), the midsagittal PF area. The ventricular width will be measured in the coronal plane according to Garel and in case of asymmetry the largest value will be taken into account. Mammilopontine distande (MPD), the level of kinking of the brain stem, medullary length, tentorial length and width of the cisterna magna will be measured. The width of the foramen magnum is defined as the distance between opisthion to the basion. Tonsillar level (TL) will be measured by drawing a perpendicular line from the foramen magnum to the lowest cerebellar portion. In the presence of cerebellar herniation the deepest portion will be used. The cerebellopontine angle will also be measured. These are all metric data and will be reported in mm. To adjust for normal changes according to gestational age, there will be a correction based on an observed/expeted ratio for the parameters.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
Related trials for Fetal Anomaly
RecruitingPhase 1
Serial Amnioinfusions as Regenerative Therapy for Pulmonary Hypoplasia
Renal Failure Congenital, Congenital Renal Anomaly Nos
Enrolling by invitationObservational study
North American Fetal Therapy Network Prospective Registry for Long-term Outcome Following Fetoscopic Endoluminal Tracheal Occlusion in Severe Left and Right Congenital Diaphragmatic Hernia
Congenital Diaphragmatic Hernia
Recruiting
Fetal Repair of Complex Gastroschisis: A Safety and Feasibility Trial
Gastroschisis
RecruitingObservational study
Growing Little PEAPODS Study
Premature Birth, Premature Infant
RecruitingObservational study
Genome Medical Sequencing for Gene Discovery
Intellectual Disabilities, Congenital Anomaly
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Fetal Anomaly and Spinal Dysraphism, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 2 inclusion and 2 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: finished, as of the sponsor's last update on 19 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
(1) assess the reliability of brain stem and posterior fossa measurements and compare the reliable ones with a normal populations (2) and between paired pre- and postsurgical fetuses (time frame: Examinations from 2011 - 2016). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Dec 2018.