Cerebellar MutismNCT03471026
Advanced MRI for Posterior Fossa Tumours
An observational study of Cerebellar Mutism and Posterior Fossa Syndrome, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Post-operative paediatric cerebellar mutism syndrome (pCMS) is a well-recognised complication of resective surgery for brain tumours of the cerebellum and fourth ventricle in children. Read more about this study
- Who is it for?
- Ages Up to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Cerebellar Mutism, Posterior Fossa Syndrome
- What is being tested?
- Advanced MRI sequences
- How many people
- 82 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 9 Apr 2018to 7 Apr 2021
- 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 Up to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Study population: All children referred to our institution with a brain tumour of the posterior fossa
Who may be able to join
- Age <18 Referred and operated upon within study period Brain tumour of cerebellum, IVth ventricle, brainstem undergoing craniotomy for resection (including re-do surgery) No restrictions as to tumour histology or grade (embryonal tumour / glioma / ependymoma) Informed consent given by parents
Who cannot join
- Non-neoplastic infratentorial lesions Claustrophobia Contraindication to MRI Pregnant female Scans missing at >2 timepoints Tumour resection surgery at another hospital if no pre- or post-operative scans available
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Great Ormond Street Hospital for Children
London, WC1N 3JH
About this study
Official title: Advanced MRI in Surgery for Posterior Fossa Tumours - Predicting Post-operative Paediatric Cerebellar Mutism Syndrome and Surgical Guidance to Avoid it
Post-operative paediatric cerebellar mutism syndrome (pCMS) is a well-recognised complication of resective surgery for brain tumours of the cerebellum and fourth ventricle in children. Occurring in around 25% of infratentorial craniotomies, it is characterised by a delayed onset of mutism and emotional lability, and may comprise motoric and cognitive cerebellar deficits. Transient mutism gives way to prolonged, and often incomplete, recovery. Neuroimaging studies are beginning to reveal anatomical and functional aberrancies in the brain of children with pCMS. The cerebellar efferent pathways are likely to be implicated as a neuroanatomical substrate in the development of pCMS, as shown by a handful of diffusion tractography studies to date. However, the pathophysiology of this condition still remains unclear. Hypoperfusion of supratentorial cortical and subcortical structures may mediate the speech and behavioural deficits seen in pCMS, and is a candidate for a causal pathophysiological mechanism.
This study aims to prospectively image children with pCMS using advanced MRI techniques including diffusion tractography and arterial spin labelling, and to correlate this with clinical descriptions of the syndrome.
All children referred to Great Ormond Street Hospital for Children with a posterior fossa brain tumour will be imaged pre-operatively, post-operatively and at delayed follow-up. In tandem with this, clinical assessments will be made of children post-operatively to ascertain which patients develop pCMS. In addition, anonymised advanced MRI data on healthy controls will be used as a comparator group.
- Conditions
- Cerebellar Mutism, Posterior Fossa Syndrome
- Being tested
- Advanced MRI sequences
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Advanced MRI sequencesDiagnostic test
Structural, diffusion and perfusion MRI sequences
| Study group | Role | What they receive |
|---|---|---|
| pCMS+ | Children undergoing infratentorial craniotomy for brain tumour resection whom develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences Receives: Diagnostic Test: Advanced MRI sequences | |
| pCMS- | Children undergoing infratentorial craniotomy for brain tumour resection whom do not develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences Receives: Diagnostic Test: Advanced MRI sequences | |
| Controls | Healthy control children whom have never undergone intracranial surgery have had advanced MRI sequences acquired Receives: Diagnostic Test: Advanced MRI sequences |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diffusion MRI tractography
To compare diffusion MRI derived tractography of the fronto-cerebellar circuitry (and associated metrics of fractional anisotropy and mean diffusivity) between patients with and without pCMS.
Measured: 1 year
Arterial Spin Labeling Perfusion MRI
To compare cerebral blood flow (a metric derived from perfusion MRI) in frontal lobe regions between patients with and without pCMS.
Measured: 1 year
Secondary outcomes (1)
Clinical measure of severity of pCMS
CMS Severity Score (Robertson 2006 JNS Peds 105: 444-451):
Clinical diagnosis of pCMS Yes / No
If yes:
Time of onset
- immediately post op
- Days 1-2
- Days 2-4
- => Day 4
Mutism
- Mild (<1wk)
- Moderate (1-4wks)
- Severe (>4wks)
Ataxia
- Mild (<1wk)
- Moderate (1-4wks)
- Severe (>4wks)
Hypotonia
- Mild (can sit or stand by <1wk)
- Moderate (can sit or stand by 1-4wks)
- Severe (can sit or stand by >4wks)
Irritability
- Mild (<1wk)
- Moderate (1-4wks)
- Severe (>4wks)
Severe = at least 2 severe features Moderate = at least 2 moderate features or 1 moderate and 1 severe Mild = anything less than above
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 posted20 Mar 2018
- Study start9 Apr 2018
- Primary completion9 Sep 2020
- Study completion7 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cerebellar MutismStudies of the same condition, open and under way.
- 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
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chris Clark, PhD, Principal investigator, University College London Institute of Child HealthKristian Aquilina, MD, FRCS, Principal investigator, Great Ormond Street HospitalSebastian M Toescu, MBChB (Hons), Principal investigator, University College London Institute of Child Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03471026
- Sponsor's protocol ID
- 17NI17
- Status last verified
- Dec 2020
- First submitted
- 23 Feb 2018
- Last updated
- 7 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Toescu SM, Hales PW, Cooper J, Dyson EW, Mankad K, Clayden JD, Aquilina K, Clark CA. Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery. AJNR Am J Neuroradiol. 2022 Oct;43(10):1508-1515. doi: 10.3174/ajnr.A7637. Epub 2022 Sep 22.
PubMed 36137658
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Advanced MRI in Surgery for Posterior Fossa Tumours - Predicting Post-operative Paediatric Cerebellar Mutism Syndrome and Surgical Guidance to Avoid it
- ClinicalTrials.gov ID
- NCT03471026
- Acronym / sponsor ID
- 17NI17
- Conditions
- Cerebellar Mutism, Posterior Fossa Syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Study start
- 9 Apr 2018 (actual)
- Primary completion
- 9 Sep 2020 (actual)
- Study completion
- 7 Apr 2021 (actual)
- First posted
- 20 Mar 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.
Post-operative paediatric cerebellar mutism syndrome (pCMS) is a well-recognised complication of resective surgery for brain tumours of the cerebellum and fourth ventricle in children. Occurring in around 25% of infratentorial craniotomies, it is characterised by a delayed onset of mutism and emotional lability, and may comprise motoric and cognitive cerebellar deficits. Transient mutism gives way to prolonged, and often incomplete, recovery. Neuroimaging studies are beginning to reveal anatomical and functional aberrancies in the brain of children with pCMS. The cerebellar efferent pathways are likely to be implicated as a neuroanatomical substrate in the development of pCMS, as shown by a handful of diffusion tractography studies to date. However, the pathophysiology of this condition still remains unclear. Hypoperfusion of supratentorial cortical and subcortical structures may mediate the speech and behavioural deficits seen in pCMS, and is a candidate for a causal pathophysiological mechanism.
This study aims to prospectively image children with pCMS using advanced MRI techniques including diffusion tractography and arterial spin labelling, and to correlate this with clinical descriptions of the syndrome.
All children referred to Great Ormond Street Hospital for Children with a posterior fossa brain tumour will be imaged pre-operatively, post-operatively and at delayed follow-up. In tandem with this, clinical assessments will be made of children post-operatively to ascertain which patients develop pCMS. In addition, anonymised advanced MRI data on healthy controls will be used as a comparator group.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| pCMS+ | – | Diagnostic Test: Advanced MRI sequencesChildren undergoing infratentorial craniotomy for brain tumour resection whom develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences |
| pCMS- | – | Diagnostic Test: Advanced MRI sequencesChildren undergoing infratentorial craniotomy for brain tumour resection whom do not develop pCMS will undergo pre-, post-operative and delayed follow-up advanced MRI sequences |
| Controls | – | Diagnostic Test: Advanced MRI sequencesHealthy control children whom have never undergone intracranial surgery have had advanced MRI sequences acquired |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
- Study population
- All children referred to our institution with a brain tumour of the posterior fossa
Key inclusion criteria (1 listed)
- Age <18 Referred and operated upon within study period Brain tumour of cerebellum, IVth ventricle, brainstem undergoing craniotomy for resection (including re-do surgery) No restrictions as to tumour histology or grade (embryonal tumour / glioma / ependymoma) Informed consent given by parents
Key exclusion criteria (1 listed)
- Non-neoplastic infratentorial lesions Claustrophobia Contraindication to MRI Pregnant female Scans missing at >2 timepoints Tumour resection surgery at another hospital if no pre- or post-operative scans available
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 |
|---|---|---|
| Advanced MRI sequencesStructural, diffusion and perfusion MRI sequences | Diagnostic test | Controls, pCMS+, pCMS- |
Primary outcome
Diffusion MRI tractography
Time frame: 1 year
To compare diffusion MRI derived tractography of the fronto-cerebellar circuitry (and associated metrics of fractional anisotropy and mean diffusivity) between patients with and without pCMS.
Arterial Spin Labeling Perfusion MRI
Time frame: 1 year
To compare cerebral blood flow (a metric derived from perfusion MRI) in frontal lobe regions between patients with and without pCMS.
1 secondary outcome
Clinical measure of severity of pCMS
Time frame: 1 year
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 7 Jul 2021.
- Derived from this study: PubMed 36137658Toescu SM, Hales PW, Cooper J, Dyson EW, Mankad K, Clayden JD, Aquilina K, Clark CA. Arterial Spin-Labeling Perfusion Metrics in Pediatric Posterior Fossa Tumor Surgery. AJNR Am J Neuroradiol. 2022 Oct;43(10):1508-1515. doi: 10.3174/ajnr.A7637. Epub 2022 Sep 22.
- Individual participant dataSharing planned: No
Related trials for Cerebellar Mutism
RecruitingObservational study
Cerebellar Mutism Syndrome Study
Infratentorial Neoplasms, Mutism
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.
Chris Clark, PhD principal investigator
University College London Institute of Child Health
Kristian Aquilina, MD, FRCS principal investigator
Great Ormond Street Hospital
Sebastian M Toescu, MBChB (Hons) principal investigator
University College London Institute of Child Health
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 Cerebellar Mutism and Posterior Fossa Syndrome, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
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 1 inclusion and 1 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 7 Jul 2021. 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 United Kingdom. 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?
Diffusion MRI tractography (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 NCT03471026, which also lists 1 linked publication.
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 7 Jul 2021.