Intellectual DisabilityRIDNCT05696912
Functional Tests to Resolve Unsolved Rare Diseases. Rares.
A study testing Ex-vivo approach concerning 25 patients and In-vitro approach concerning 25 patients in people with Intellectual Disability and Rubinstein-Taybi Syndrome, run by University Hospital, Bordeaux at 1 site in France.
Trial summary
Rares diseases are a heterogeneous group of conditions which need important tools for diagnosis. The use of high-throughput sequencing is able to diagnose half of the patients. For the other part it is impossible to conclude due to the presence of variants of unknown significance (VOUS). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Intellectual Disability, Rubinstein-Taybi Syndrome, Cystic Fibrosis
- What is being tested?
- Ex-vivo approach concerning 25 patients and In-vitro approach concerning 25 patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 30 Jan 2023to Feb 2025
- Phase
- Interventional
- 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
Who may be able to join
- Minor and adult patient.
- Registered for the social security system.
- Informed consent signed by patient or parent of a minor patient.
- Patient affected by one of the rare diseases studied (albinism, congenital heart defect, cystic fibrosis, neurodevelopmental disease)
- Patient bearing variants of unknown significance (VOUS)
Who cannot join
- Refusal to participate in research protocol.
- Patient under administrative supervision
- Pregnant or nursing women
Trial locations and contacts
1 site in 1 country.
Ndeye-Fatou NGOM contact
France1 site, 1 recruiting
- Recruiting
Hopital Pellegrin
Bordeaux, 33000
Vincent MICHAUD, Dr, vincent.michaud@chu-bordeaux.fr
About this study
Official title: Resolving Unsolved Rare Diseases : Functional Tests and New Diagnosis Strategy to Study Genetic Variants From High-throughput Sequencing (RID)
Rares diseases are a heterogeneous group of conditions which need important tools for diagnosis.
The use of high-throughput sequencing is able to diagnose half of the patients. For the other part it is impossible to conclude due to the presence of variants of unknown significance (VOUS). Functional analysis are needed to bring strong argument to reclassify variants as pathogenic or benign. The main objective is to evaluate the diagnosis yield of this strategy.
Read the detailed description
The main objective is the improvement of the diagnosis of rare genetic diseases. The investigator lab is expert for diagnosis of some rare diseases such as neurodevelopmental disorder, albinism, cystic fibrosis and congenital heart defect. Actually with implementation of high-throughput sequencing for diagnosis, a high number of genetic variants are found and need to be interpretated. The ACMG classification is used to classify variants with argument of variant frequency, predicted effect on protein and in-silico prediction. Functional evidence is a strong argument to help classify VOUS. The investigators propose the use of RNA-Seq, minigene and luciferase assay for study of VOUS to bring argument to classify them as benign or pathogenic.
- Conditions
- Intellectual Disability, Rubinstein-Taybi Syndrome, Cystic Fibrosis, Congenital Heart Defect, Periventricular Nodular Heterotopia, Neurodegeneration With Brain Iron Accumulation (NBIA)
- Being tested
- Ex-vivo approach concerning 25 patients, In-vitro approach concerning 25 patients
- Keywords
- Variant of unknown significance, Functional genetics, Translational research, RNAseq, Gene expression regulation
- Medical subject headings
- Intellectual Disability, Rubinstein-Taybi Syndrome, Cystic Fibrosis, Heart Defects, Congenital, Periventricular Nodular Heterotopia, Pantothenate Kinase-Associated Neurodegeneration, Albinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ex-vivo approach concerning 25 patientsGenetic
Ex-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis
In-vitro approach concerning 25 patientsGenetic
In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay
| Study group | Role | What they receive |
|---|---|---|
| Ex-vivo and In-vitro approach | Other | Ex-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis.
In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay Receives: Genetic: Ex-vivo approach concerning 25 patients; Genetic: In-vitro approach concerning 25 patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of VOUS reclassified as pathogenic (class 5) or benign (class 1)
It's the proportion of VOUS that could be definitively reclassified as pathogenic (class 5) or benign (class 1) according to the ACMG classification (Richards et al., 2015 and Appendix 1). Indeed currently only variants considered as pathogenic or probably pathogenic make it possible to confirm a diagnosis and to propose genetic offer genetic counseling to families and perform a prenatal diagnosis. This is an evaluation that will be carried out at the end of the analyses carried out
Measured: Inclusion visit
Secondary outcomes (5)
Pre-analysis process : Time of sample transport to the laboratory
Time of transport to the laboratory. To calculate this time, the time of collection and the time of receipt by the and the time of reception by the molecular genetics technician will be recorded
Measured: Inclusion visit
Pre-analysis process : Quality of RNA extraction (RNA Integrity Number, RIN)
RNA quality measurement by RIN (RNA integrity number): very good >7, good >/=5, poor <5. Only RNA with RIN >5 will be retained.
Measured: Inclusion visit
Praticability :Characteristics and number of CPU (Central Processing Unit)
Evaluation of bioinformatic ressources by measure of number of CPU needed and turnaround time for processing data
Measured: Inclusion visit
Praticability : Training time of Biologists for interpretation
Evaluation of training time needed to interpret the data
Measured: Inclusion visit
Global cost
Evaluation of cost of global analyse and each test
Measured: Inclusion visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2023
- Study start30 Jan 2023
- Primary completionFeb 2025 (estimated)
- Study completionFeb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intellectual DisabilityStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Ex-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis. In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay.
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent MICHAUD, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05696912
- Sponsor's protocol ID
- CHU BX 2021/40
- Acronym
- RID
- Status last verified
- Feb 2024
- First submitted
- 7 Dec 2022
- Last updated
- 21 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resolving Unsolved Rare Diseases : Functional Tests and New Diagnosis Strategy to Study Genetic Variants From High-throughput Sequencing (RID)
- ClinicalTrials.gov ID
- NCT05696912
- Acronym / sponsor ID
- RID / CHU BX 2021/40
- Conditions
- Intellectual Disability, Rubinstein-Taybi Syndrome, Cystic Fibrosis, Congenital Heart Defect, Periventricular Nodular Heterotopia, Neurodegeneration With Brain Iron Accumulation (NBIA)
- Keywords
- Variant of unknown significance, Functional genetics, Translational research, RNAseq, Gene expression regulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 30 Jan 2023 (actual)
- Primary completion
- Feb 2025 (estimated)
- Study completion
- Feb 2025 (estimated)
- First posted
- 25 Jan 2023 (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.
Rares diseases are a heterogeneous group of conditions which need important tools for diagnosis.
The use of high-throughput sequencing is able to diagnose half of the patients. For the other part it is impossible to conclude due to the presence of variants of unknown significance (VOUS). Functional analysis are needed to bring strong argument to reclassify variants as pathogenic or benign. The main objective is to evaluate the diagnosis yield of this strategy.
Detailed description
The main objective is the improvement of the diagnosis of rare genetic diseases. The investigator lab is expert for diagnosis of some rare diseases such as neurodevelopmental disorder, albinism, cystic fibrosis and congenital heart defect. Actually with implementation of high-throughput sequencing for diagnosis, a high number of genetic variants are found and need to be interpretated. The ACMG classification is used to classify variants with argument of variant frequency, predicted effect on protein and in-silico prediction. Functional evidence is a strong argument to help classify VOUS. The investigators propose the use of RNA-Seq, minigene and luciferase assay for study of VOUS to bring argument to classify them as benign or pathogenic.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Ex-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis. In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay.
| Arm | Type | Receives |
|---|---|---|
| Ex-vivo and In-vitro approach | Other | Genetic: Ex-vivo approach concerning 25 patients, Genetic: In-vitro approach concerning 25 patientsEx-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis. In-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Minor and adult patient.
- Registered for the social security system.
- Informed consent signed by patient or parent of a minor patient.
- Patient affected by one of the rare diseases studied (albinism, congenital heart defect, cystic fibrosis, neurodevelopmental disease)
- Patient bearing variants of unknown significance (VOUS)
Key exclusion criteria (3 listed)
- Refusal to participate in research protocol.
- Patient under administrative supervision
- Pregnant or nursing women
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 |
|---|---|---|
| Ex-vivo approach concerning 25 patientsEx-vivo approach concerning 25 patients with blood sample in PAXgene tubes or skin biopsy and RNA-Seq analysis | Genetic | Ex-vivo and In-vitro approach |
| In-vitro approach concerning 25 patientsIn-vitro approach concerning 25 patients without specific samples needed for analysis in minigene or luciferase assay | Genetic | Ex-vivo and In-vitro approach |
Primary outcome
Proportion of VOUS reclassified as pathogenic (class 5) or benign (class 1)
Time frame: Inclusion visit
It's the proportion of VOUS that could be definitively reclassified as pathogenic (class 5) or benign (class 1) according to the ACMG classification (Richards et al., 2015 and Appendix 1). Indeed currently only variants considered as pathogenic or probably pathogenic make it possible to confirm a diagnosis and to propose genetic offer genetic counseling to families and perform a prenatal diagnosis. This is an evaluation that will be carried out at the end of the analyses carried out
5 secondary outcomes
Pre-analysis process : Time of sample transport to the laboratory
Time frame: Inclusion visit
Pre-analysis process : Quality of RNA extraction (RNA Integrity Number, RIN)
Time frame: Inclusion visit
Praticability :Characteristics and number of CPU (Central Processing Unit)
Time frame: Inclusion visit
Praticability : Training time of Biologists for interpretation
Time frame: Inclusion visit
Global cost
Time frame: Inclusion visit
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2024.
- Individual participant dataSharing planned: No
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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.
Ndeye-Fatou NGOM contact
Vincent MICHAUD principal investigator
University Hospital, Bordeaux
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ex-vivo approach concerning 25 patients and In-vitro approach concerning 25 patients in people with Intellectual Disability and Rubinstein-Taybi Syndrome, run by University Hospital, Bordeaux 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 5 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 21 Feb 2024. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vincent MICHAUD (+335 57 82 01 93, vincent.michaud@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of VOUS reclassified as pathogenic (class 5) or benign (class 1) (time frame: Inclusion visit). 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 21 Feb 2024.