Rare Intellectual DisabilitiesMIDRIDNCT03635294
Multi-Omics and IPSCs to Improve Diagnosis of Rare Intellectual Disabilities
A study testing Blood sample in people with Rare Intellectual Disabilities, run by University Hospital, Angers at 6 sites in France.
Trial summary
Background Genetic factors play a major role in intellectual disability (ID) but the underlying cause is not determined in many cases. This proposal is the continuation of the previous interregional project HUGODIMS, the aim of which was to perform whole exome sequencing (WES) in 69 thoroughly selected simplex ID… Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Rare Intellectual Disabilities
- What is being tested?
- Blood sample
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 6 sitesFrance
- Study dates
- 9 Jan 2019to 11 Feb 2020
- 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 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 3 Whole Genome Sequencing negative cases
- 3 positive controls bearing distinct mutations in CAMK2a
Who cannot join
- no informed consent/refusal
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
CHU Angers
Angers
HCL Lyon
Bron
CHU de Bourgogne
Dijon
CHU Nantes
Nantes
CHU Poitiers
Poitiers
CHU Rennes
Rennes
About this study
Official title: Multi-Omics and IPSCs to Improve the Diagnosis of Rare Intellectual Disabilities
Background Genetic factors play a major role in intellectual disability (ID) but the underlying cause is not determined in many cases.
This proposal is the continuation of the previous interregional project HUGODIMS, the aim of which was to perform whole exome sequencing (WES) in 69 thoroughly selected simplex ID parent-child trios. Thanks to HUGODIMS consortium, the underlying genetic cause of ID was determined or highly suspected in 48 cases (69.5%) and 7 novel ID genes were identified.
Read more
Hypothesis Investigators hypothesize that an approach combining genomics, transcriptomics, metabolomics and morphological analyses performed on induced pluripotent stem cell (iPSC)-derived neural cells would improve diagnosis of ID. The current proposal is therefore a proof-of concept project aiming at assessing the relevance and effectiveness of this multi-omics approach.
Aims and Methods Ten individuals with ID recruited through HUGODIMS, in whom WES have failed to identify pathogenic variants will be included.
The workflow is the following:
- Whole genome sequencing (WGS) (Nantes) of these 10 negative trios.
- Bio-informatics analyses
- In 3 WGS negative cases, 3 positive controls bearing distinct mutations in CAMK2a (a novel ID gene identified thanks to HUGODIMS), and 3 healthy negative controls:
- Derivation of induced pluripotent stem cell (iPSC)-derived neural progenitors (iPSC core facility at Nantes)
- Targeted and non-targeted metabolomics analyses performed on iPSC-derived neuronal cells (Angers)
- RNA sequencing performed on the 9 cell lines (Rennes)
- Morphological analyses of differentiated neuronal cell lines derived from 3 affected individuals and 3 positive controls bearing CMK2a mutations (Tours)
- Integration and validation of data from multi-omics and morphological approaches
Expected results and impact Investigatrors expect that this approach combining multi-omics and iPSC will help to improve diagnosis and understanding of genetic ID of unknown cause
- Conditions
- Rare Intellectual Disabilities
- Being tested
- Blood sample
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood sampleOther
combining genomics, transcriptomics, metabolomics and morphological analyses performed on induced pluripotent stem cell (iPSC)-derived neural cells
| Study group | Role | What they receive |
|---|---|---|
| Blood sample | Experimental | Blood sample for analyses Receives: Other: Blood sample |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the relevance and effectiveness of a multi-omics approach to the diagnosis of ID of unknown genetic origin.
Whole genome sequencing : de novo variants in non-coding regions of the genome, WGS will be performed using the HiSeq X Five System 5; Bionformatics analysis of WGS data; neuronal progenitors derived from iPSC
Measured: Day 1
Secondary outcomes (2)
The assessment of metabolomics consequences of CAMK2a mutations in human neuronal progenitors and differentiated neuronal cell lines
Coupled to high-resolution mass spectrometry ; Transcriptomics analyses: quality of the RNA will be evaluated with the Bioanalyzer (Agilent) on the basis of the RIN (RNA integrity number) as well as by taking into account the DV200, i.e. the percentage of RNA fragments with more than 200 nucleotides Non-targeted metabolomic analyses will be performed using a method based on ultra-high-performance liquid chromatography Flow injection analysis-tandem mass spectrometry for quantifying acylcarnitines, glycerophospholipids, sphingolipids and sugar, whereas liquid chromatography
Measured: Day 1
The assessment of morphological consequences of CAMK2a mutations in human neuronal progenitors and differentiated neuronal cell lines
immunocytochemistry and protein expression approaches using confocal microscopy and Western blotting with antibodies specific for proteins expressed in neurons (MAP2, Tubulin beta 3, PSD95, SNAP25), astrocytes (GFAP) or oligodendrocytes (Gal-C)
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start9 Jan 2019
- Primary completion11 Feb 2020
- Study completion11 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rare Intellectual DisabilitiesStudies of the same condition, open and under way.
- More trials run by University Hospital, AngersThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Angers
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03635294
- Sponsor's protocol ID
- 49RC17_0224
- Acronym
- MIDRID
- Status last verified
- Aug 2024
- First submitted
- 10 Aug 2018
- Last updated
- 14 Aug 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 14 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Omics and IPSCs to Improve the Diagnosis of Rare Intellectual Disabilities
- ClinicalTrials.gov ID
- NCT03635294
- Acronym / sponsor ID
- MIDRID / 49RC17_0224
- Conditions
- Rare Intellectual Disabilities
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University Hospital, AngersOther government
- Study start
- 9 Jan 2019 (actual)
- Primary completion
- 11 Feb 2020 (actual)
- Study completion
- 11 Feb 2020 (actual)
- First posted
- 17 Aug 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.
Background Genetic factors play a major role in intellectual disability (ID) but the underlying cause is not determined in many cases.
This proposal is the continuation of the previous interregional project HUGODIMS, the aim of which was to perform whole exome sequencing (WES) in 69 thoroughly selected simplex ID parent-child trios. Thanks to HUGODIMS consortium, the underlying genetic cause of ID was determined or highly suspected in 48 cases (69.5%) and 7 novel ID genes were identified.
Hypothesis Investigators hypothesize that an approach combining genomics, transcriptomics, metabolomics and morphological analyses performed on induced pluripotent stem cell (iPSC)-derived neural cells would improve diagnosis of ID. The current proposal is therefore a proof-of concept project aiming at assessing the relevance and effectiveness of this multi-omics approach.
Aims and Methods Ten individuals with ID recruited through HUGODIMS, in whom WES have failed to identify pathogenic variants will be included.
The workflow is the following:
- Whole genome sequencing (WGS) (Nantes) of these 10 negative trios.
- Bio-informatics analyses
- In 3 WGS negative cases, 3 positive controls bearing distinct mutations in CAMK2a (a novel ID gene identified thanks to HUGODIMS), and 3 healthy negative controls:
- Derivation of induced pluripotent stem cell (iPSC)-derived neural progenitors (iPSC core facility at Nantes)
- Targeted and non-targeted metabolomics analyses performed on iPSC-derived neuronal cells (Angers)
- RNA sequencing performed on the 9 cell lines (Rennes)
- Morphological analyses of differentiated neuronal cell lines derived from 3 affected individuals and 3 positive controls bearing CMK2a mutations (Tours)
- Integration and validation of data from multi-omics and morphological approaches
Expected results and impact Investigatrors expect that this approach combining multi-omics and iPSC will help to improve diagnosis and understanding of genetic ID of unknown cause
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Blood sample | Experimental | Other: Blood sampleBlood sample for analyses |
Who may qualify
- Ages
- 2 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 3 Whole Genome Sequencing negative cases
- 3 positive controls bearing distinct mutations in CAMK2a
Key exclusion criteria (1 listed)
- no informed consent/refusal
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 |
|---|---|---|
| Blood samplecombining genomics, transcriptomics, metabolomics and morphological analyses performed on induced pluripotent stem cell (iPSC)-derived neural cells | Other | Blood sample |
Primary outcome
To evaluate the relevance and effectiveness of a multi-omics approach to the diagnosis of ID of unknown genetic origin.
Time frame: Day 1
Whole genome sequencing : de novo variants in non-coding regions of the genome, WGS will be performed using the HiSeq X Five System 5; Bionformatics analysis of WGS data; neuronal progenitors derived from iPSC
2 secondary outcomes
The assessment of metabolomics consequences of CAMK2a mutations in human neuronal progenitors and differentiated neuronal cell lines
Time frame: Day 1
The assessment of morphological consequences of CAMK2a mutations in human neuronal progenitors and differentiated neuronal cell lines
Time frame: Day 1
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 14 Aug 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.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood sample in people with Rare Intellectual Disabilities, run by University Hospital, Angers at 6 sites 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 2 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 14 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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?
To evaluate the relevance and effectiveness of a multi-omics approach to the diagnosis of ID of unknown genetic origin. (time frame: Day 1). 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 14 Aug 2024.