Intellectual Developmental DisorderNCT04541927
Better Delineation of BCL11B Related Phenotype and Epigenetic Signature.
An observational study of Intellectual Developmental Disorder and BCL11B Related Disorder, run by University Hospital, Montpellier at 1 site in France.
Trial summary
BCL11B related disorder, also known as Gabriele-de-Vries syndrome, is mainly characterised by developmental delay (DD) and intellectual disability (ID), ranging from mild to severe, and neuroimaging abnormalities. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Intellectual Developmental Disorder, BCL11B Related Disorder
- What is being tested?
- Epigenetic signatures
- How many people
- 10 participants
- Where
- 1 siteFrance
- Study dates
- 1 Nov 2019to 1 Dec 2020
- 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
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Individuals with BCL11B intragenic pathogenic SNV (Single Nucleotide Variant)
Who may be able to join
- BCL11B intragenic pathogenic SNV (Single Nucleotide Variant)
Who cannot join
- no pathogenic SNV in BCL11B
- no consent for the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: BCL11B Related Disorder : Clinical Phenotype, Neuropsychological Profile, Brain MRI Characteristics and Epigenetic Signatures.
BCL11B related disorder, also known as Gabriele-de-Vries syndrome, is mainly characterised by developmental delay (DD) and intellectual disability (ID), ranging from mild to severe, and neuroimaging abnormalities.
The aims of this study are first to better delineate the clinical phenotype, as well as the neuropsychological profile, and the brain MRI characteristics; and, second, to study the epigenetic signatures in a cohort of individuals with BCL11B intragenic pathogenic variants. This work will conduct to a MD thesis of a clinical resident geneticist in France.
Read more
Physician that will participate will fill an Excel sheet regarding the clinical and neuropsychological assessment. The investigators will be also happy to have either CD-ROM or a link to have access to the brain MRI data as well as a DNA sample with a minimum 0.5ug of peripheral blood genomic DNA. The investigators will gather the DNA in Montpellier genetic lab (Dr Mouna BARAT) and send the batch to the Dr Sadikovic' lab.
Between 2019 and 2020, The investigators have already recruited data from individuals with BCL11B pathogenic variants from several European and American genetic centres.
Read the detailed description
The investigators aim to better understand and delineate the genetic syndrome BCL11B (a.k.a. Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities syndrome or IDDSFTA).
This genetic disorder was described in June 2017 in the American Journal of Human Genetics (PMID 28575647).
Since this first publication of 23 individuals carrying the pathogenic mutation BCL11B, another individual has been reported in the literature (PMID 30549423).
In addition, the first paper focused on the clinical description as well as the effect of pathogenic BCL11B variations in chromatin regulation.
The investigators are seeking to better define the phenotype of individuals with pathogenic variants of BCL11B, to better understand intellectual functioning as well as the strengths and weaknesses of intellectual functioning by collecting standardized neuropsychological assessments already performed such as WPPSI/WISC and WAIS. For this purpose, The investigators will gather clinical and neuropsychological data already carried out in the context of care.
The investigators also aim to gather the cerebral MRI scans already performed in order to better delimit the cerebral anomalies observed in individuals and if the sequence is adapted, The investigators will perform VBM studies.
Finally, The investigators will attempt to identify an epigenetic signature in this genetic disease. To this end, The investigators will collect genomic DNA from peripheral blood already collected for genetic analysis and send an anonymized batch of samples to our collaborator, Dr. Bekim Sadicovik. Dr. Bekim Sadicovik and his team will compare the epigenetic DNA methylation-type markers with the corresponding sex and age controls. If specific probes are abnormally methylated in BCL11B individuals, this will determine a disease-specific epigenetic signature. The investigators will then be able to propose an epigenetic signature for individuals with uncharacterized BCL11B variations (class 3, VUS). This method will make it possible to define whether the variation is responsible for the disease or not without going through functional analysis steps that are difficult to implement routinely.
The expected benefits are a better understanding of BCL11B disease, keys to neuropsychological rehabilitation, a better understanding of human brain functions, the possibility of proposing an epigenetic signature for people in whom it is not possible to decide whether a variation in the BCL11B gene is pathological or not
- Being tested
- Epigenetic signatures
- Keywords
- BCL11B related disorder
- Medical subject headings
- Intellectual Disability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Epigenetic signaturesGenetic
Epigenetic signatures (Dr Sadikovic' lab, London, Ontario, Canada)
| Study group | Role | What they receive |
|---|---|---|
| BCL11B | BCL11B intragenic pathogenic variant Receives: Genetic: Epigenetic signatures |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neuropsychological phenotype
BCL11B related clinical and neuropsychological phenotype. Neuropsychological phenotype will be assessed using Wechsler scales. The phenotype of individuals will be assessed using a questionnaire sent to their geneticist
Measured: 1 day
Measurement and comparison of the methylation of the cpg sites
Epigenetic signature will be investigated by measurement and comparison of the methylation of the cpg sites
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start1 Nov 2019
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intellectual Developmental DisorderStudies of the same condition, open and under way.
- More trials run by University Hospital, MontpellierThe 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
- Other
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David GENEVIEVE, Principal investigator, Department of Medical Genetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04541927
- Sponsor's protocol ID
- RECHMPL20_0472
- Status last verified
- Dec 2020
- First submitted
- 1 Sep 2020
- Last updated
- 29 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: NC
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- BCL11B Related Disorder : Clinical Phenotype, Neuropsychological Profile, Brain MRI Characteristics and Epigenetic Signatures.
- ClinicalTrials.gov ID
- NCT04541927
- Acronym / sponsor ID
- RECHMPL20_0472
- Keywords
- BCL11B related disorder
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Study start
- 1 Nov 2019 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 9 Sep 2020 (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.
BCL11B related disorder, also known as Gabriele-de-Vries syndrome, is mainly characterised by developmental delay (DD) and intellectual disability (ID), ranging from mild to severe, and neuroimaging abnormalities.
The aims of this study are first to better delineate the clinical phenotype, as well as the neuropsychological profile, and the brain MRI characteristics; and, second, to study the epigenetic signatures in a cohort of individuals with BCL11B intragenic pathogenic variants. This work will conduct to a MD thesis of a clinical resident geneticist in France.
Physician that will participate will fill an Excel sheet regarding the clinical and neuropsychological assessment. The investigators will be also happy to have either CD-ROM or a link to have access to the brain MRI data as well as a DNA sample with a minimum 0.5ug of peripheral blood genomic DNA. The investigators will gather the DNA in Montpellier genetic lab (Dr Mouna BARAT) and send the batch to the Dr Sadikovic' lab.
Between 2019 and 2020, The investigators have already recruited data from individuals with BCL11B pathogenic variants from several European and American genetic centres.
Detailed description
The investigators aim to better understand and delineate the genetic syndrome BCL11B (a.k.a. Intellectual developmental disorder with dysmorphic facies, speech delay, and T-cell abnormalities syndrome or IDDSFTA).
This genetic disorder was described in June 2017 in the American Journal of Human Genetics (PMID 28575647).
Since this first publication of 23 individuals carrying the pathogenic mutation BCL11B, another individual has been reported in the literature (PMID 30549423).
In addition, the first paper focused on the clinical description as well as the effect of pathogenic BCL11B variations in chromatin regulation.
The investigators are seeking to better define the phenotype of individuals with pathogenic variants of BCL11B, to better understand intellectual functioning as well as the strengths and weaknesses of intellectual functioning by collecting standardized neuropsychological assessments already performed such as WPPSI/WISC and WAIS. For this purpose, The investigators will gather clinical and neuropsychological data already carried out in the context of care.
The investigators also aim to gather the cerebral MRI scans already performed in order to better delimit the cerebral anomalies observed in individuals and if the sequence is adapted, The investigators will perform VBM studies.
Finally, The investigators will attempt to identify an epigenetic signature in this genetic disease. To this end, The investigators will collect genomic DNA from peripheral blood already collected for genetic analysis and send an anonymized batch of samples to our collaborator, Dr. Bekim Sadicovik. Dr. Bekim Sadicovik and his team will compare the epigenetic DNA methylation-type markers with the corresponding sex and age controls. If specific probes are abnormally methylated in BCL11B individuals, this will determine a disease-specific epigenetic signature. The investigators will then be able to propose an epigenetic signature for individuals with uncharacterized BCL11B variations (class 3, VUS). This method will make it possible to define whether the variation is responsible for the disease or not without going through functional analysis steps that are difficult to implement routinely.
The expected benefits are a better understanding of BCL11B disease, keys to neuropsychological rehabilitation, a better understanding of human brain functions, the possibility of proposing an epigenetic signature for people in whom it is not possible to decide whether a variation in the BCL11B gene is pathological or not
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BCL11B | – | Genetic: Epigenetic signaturesBCL11B intragenic pathogenic variant |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Individuals with BCL11B intragenic pathogenic SNV (Single Nucleotide Variant)
Key inclusion criteria (1 listed)
- BCL11B intragenic pathogenic SNV (Single Nucleotide Variant)
Key exclusion criteria (2 listed)
- no pathogenic SNV in BCL11B
- no consent for the study
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 |
|---|---|---|
| Epigenetic signaturesEpigenetic signatures (Dr Sadikovic' lab, London, Ontario, Canada) | Genetic | BCL11B |
Primary outcome
Neuropsychological phenotype
Time frame: 1 day
BCL11B related clinical and neuropsychological phenotype. Neuropsychological phenotype will be assessed using Wechsler scales. The phenotype of individuals will be assessed using a questionnaire sent to their geneticist
Measurement and comparison of the methylation of the cpg sites
Time frame: 1 day
Epigenetic signature will be investigated by measurement and comparison of the methylation of the cpg sites
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 29 Dec 2020.
- Individual participant dataSharing planned: Undecided. NC
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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. This study is not recruiting at the moment.
David GENEVIEVE principal investigator
Department of Medical Genetics
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 Intellectual Developmental Disorder and BCL11B Related Disorder, run by University Hospital, Montpellier at 1 site in France.
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 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 29 Dec 2020. 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 France. 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?
Neuropsychological phenotype (time frame: 1 day). 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?
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 29 Dec 2020.