Patients With Intellectual Disabilities Without an Obvious Clinical DiagnosisDI-WANCT03857997
Contribution of High Throughput RNA Sequencing Combined With Sequencing of Whole Genomes in the Diagnosis of Intellectual Disability
An observational study of Patients With Intellectual Disabilities Without an Obvious Clinical Diagnosis and Patients With Normal Array CGH and Previous Negative Genetic Investigations (WES-solo or WES-trio), run by Centre Hospitalier Universitaire Dijon at 1 site in France.
Trial summary
Intellectual disability (ID) is a clinically and genetically heterogeneous condition that often results in a diagnostic odyssey. The deployment of high throughput sequencing (HTS) and in particular exome sequencing (WES) has made it possible to identify many genes responsible for ID. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Patients With Intellectual Disabilities Without an Obvious Clinical Diagnosis, Patients With Normal Array CGH and Previous Negative Genetic Investigations (WES-solo or WES-trio)
- What is being tested?
- Patient blood sampling and Parents blood sampling
- How many people
- 62 participants
- Where
- 1 siteFrance
- Study dates
- 4 Feb 2019to 2 Feb 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: patient in consultation for intellectual disability
Who may be able to join
- individuals with intellectual disabilities without an obvious clinical diagnosis,
- idividuals with normal array CGH and previous negative genetic explorations (WES-solo or WES-trio),
- individuals whose sampling is possible in the index case and the 2 biological parents in order to carry out a trio sequencing,
- individuals having given their written consent (consent of the legal representative(s) if the patient is a minor or incapacitated),
- individuals whose biological parents have given their consent to be sampled,
- individuals affiliated to or beneficiaries of the national health insurance system.
Who cannot join
- pregnant or breastfeeding woman,
- individuals for whom there is a diagnostic hypothesis considered highly probable and for which a molecular test routinely available has a lower cost than the genome,
- individual whose parents refuse to participate in the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Contribution of High Throughput RNA Sequencing Combined With Sequencing of Whole Genomes in the Diagnosis of Intellectual Disability.
Intellectual disability (ID) is a clinically and genetically heterogeneous condition that often results in a diagnostic odyssey.
The deployment of high throughput sequencing (HTS) and in particular exome sequencing (WES) has made it possible to identify many genes responsible for ID. However, the WES does not identify the cause of ID in about two-thirds of patients, due to, for example, the uneven depth and coverage of all exons, or the location of variants in non-exonic areas. It has thus been shown that genome sequencing (WGS), which is still rarely used because it is more complex and costly, would be more efficient, with an expected diagnostic rate of around 60%.
Read more
In response to the massive contribution of HTS in the diagnosis of patients suffering from rare diseases, France has launched the France Plan Médecine Genomique 2025 (PFMG2025) to deploy HTS platforms, which will be able to carry out WGS, WES and RNA sequencing (RNA-seq), and pilot studies to define the modalities for prescribing these examinations. Two cost-effectiveness evaluations of these technologies, in comparison with the current strategy for diagnosis of ID, are currently underway or planned in the short term in France: 1) PRME DISSEQ, comparing the large DI459 panel versus WES, 2) the DEFIDIAG pilot study of the PFMG2025 comparing WGS, in trio versus solo, versus current strategy. However, there are no studies examining the place of the RNA-seq in the ID diagnostic decision tree.
However, some pathogenic variations are likely to have an effect on transcription. WES/WGS can detect them but are not able to affirm their pathogenicity because it focuses on genomic DNA. Only the RNA-seq makes it possible to study the transcription of candidate genes on a large scale, providing an additional level of evidence on both known genes in human pathology (OMIM) and candidate genes.
The RNA-seq would increase the diagnostic rate from 10% to 35% in addition to the WGS in negative patients with first-line approaches (including WES) and thus optimize management by reducing diagnostic delays as part of a personalized care pathway.
- Conditions
- Patients With Intellectual Disabilities Without an Obvious Clinical Diagnosis, Patients With Normal Array CGH and Previous Negative Genetic Investigations (WES-solo or WES-trio)
- Being tested
- Patient blood sampling, Parents blood sampling
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Patient blood samplingBiological
sequencing by WGS and RNA-seq
Parents blood samplingBiological
sequencing by WGS
| Study group | Role | What they receive |
|---|---|---|
| Patients | Not described Receives: Biological: Patient blood sampling | |
| Parents | Not described Receives: Biological: Parents blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
additional etiological diagnosis of intellectual disability
Identification of additional etiological diagnosis of intellectual disability by the WGS-trio + RNA-seq vs WGS trio strategy.
Measured: At the time of analysis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2019
- Study start4 Feb 2019
- Primary completion27 Dec 2019
- Study completion2 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Patients With Intellectual Disabilities Without an Obvious Clinical DiagnosisStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire DijonThe 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
- Prospective
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire Dijon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03857997
- Sponsor's protocol ID
- TRAN MAU-THEM PHRCI 2017
- Acronym
- DI-WA
- Status last verified
- Sep 2021
- First submitted
- 25 Feb 2019
- Last updated
- 1 Oct 2021
- 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 1 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Contribution of High Throughput RNA Sequencing Combined With Sequencing of Whole Genomes in the Diagnosis of Intellectual Disability.
- ClinicalTrials.gov ID
- NCT03857997
- Acronym / sponsor ID
- DI-WA / TRAN MAU-THEM PHRCI 2017
- Conditions
- Patients With Intellectual Disabilities Without an Obvious Clinical Diagnosis, Patients With Normal Array CGH and Previous Negative Genetic Investigations (WES-solo or WES-trio)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire DijonUniversity, hospital or other
- Study start
- 4 Feb 2019 (actual)
- Primary completion
- 27 Dec 2019 (actual)
- Study completion
- 2 Feb 2021 (actual)
- First posted
- 28 Feb 2019 (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.
Intellectual disability (ID) is a clinically and genetically heterogeneous condition that often results in a diagnostic odyssey.
The deployment of high throughput sequencing (HTS) and in particular exome sequencing (WES) has made it possible to identify many genes responsible for ID. However, the WES does not identify the cause of ID in about two-thirds of patients, due to, for example, the uneven depth and coverage of all exons, or the location of variants in non-exonic areas. It has thus been shown that genome sequencing (WGS), which is still rarely used because it is more complex and costly, would be more efficient, with an expected diagnostic rate of around 60%.
In response to the massive contribution of HTS in the diagnosis of patients suffering from rare diseases, France has launched the France Plan Médecine Genomique 2025 (PFMG2025) to deploy HTS platforms, which will be able to carry out WGS, WES and RNA sequencing (RNA-seq), and pilot studies to define the modalities for prescribing these examinations. Two cost-effectiveness evaluations of these technologies, in comparison with the current strategy for diagnosis of ID, are currently underway or planned in the short term in France: 1) PRME DISSEQ, comparing the large DI459 panel versus WES, 2) the DEFIDIAG pilot study of the PFMG2025 comparing WGS, in trio versus solo, versus current strategy. However, there are no studies examining the place of the RNA-seq in the ID diagnostic decision tree.
However, some pathogenic variations are likely to have an effect on transcription. WES/WGS can detect them but are not able to affirm their pathogenicity because it focuses on genomic DNA. Only the RNA-seq makes it possible to study the transcription of candidate genes on a large scale, providing an additional level of evidence on both known genes in human pathology (OMIM) and candidate genes.
The RNA-seq would increase the diagnostic rate from 10% to 35% in addition to the WGS in negative patients with first-line approaches (including WES) and thus optimize management by reducing diagnostic delays as part of a personalized care pathway.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients | – | Biological: Patient blood sampling |
| Parents | – | Biological: Parents blood sampling |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patient in consultation for intellectual disability
Key inclusion criteria (6 listed)
- individuals with intellectual disabilities without an obvious clinical diagnosis,
- idividuals with normal array CGH and previous negative genetic explorations (WES-solo or WES-trio),
- individuals whose sampling is possible in the index case and the 2 biological parents in order to carry out a trio sequencing,
- individuals having given their written consent (consent of the legal representative(s) if the patient is a minor or incapacitated),
- individuals whose biological parents have given their consent to be sampled,
Key exclusion criteria (3 listed)
- pregnant or breastfeeding woman,
- individuals for whom there is a diagnostic hypothesis considered highly probable and for which a molecular test routinely available has a lower cost than the genome,
- individual whose parents refuse to participate in 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 |
|---|---|---|
| Patient blood samplingsequencing by WGS and RNA-seq | Biological | Patients |
| Parents blood samplingsequencing by WGS | Biological | Parents |
Primary outcome
additional etiological diagnosis of intellectual disability
Time frame: At the time of analysis
Identification of additional etiological diagnosis of intellectual disability by the WGS-trio + RNA-seq vs WGS trio strategy.
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 1 Oct 2021.
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 Patients With Intellectual Disabilities Without an Obvious Clinical Diagnosis and Patients With Normal Array CGH and Previous Negative Genetic Investigations (WES-solo or WES-trio), run by Centre Hospitalier Universitaire Dijon 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 6 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: finished, as of the sponsor's last update on 1 Oct 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 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?
additional etiological diagnosis of intellectual disability (time frame: At the time of analysis). 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 1 Oct 2021.