Genetic DiseaseHiFi-NDDNCT05643274
Use of Long Read Genome Sequencing in Patients Suffering From Neurodevelopmental Troubles
An observational study of Genetic Disease and Neurologic Disorder, run by Nantes University Hospital at 5 sites in France.
Trial summary
Patients with neurodevelopmental diseases and their families need to identify the genetic cause of the disease to allow for recognition of the disability, genetic counseling, and possible hope for participation in therapeutic research studies. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Genetic Disease, Neurologic Disorder, Developmental Delay Disorder
- How many people
- 10 participants
- Where
- 5 sitesFrance
- Study dates
- 19 Dec 2022to 8 Mar 2024
- 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
- Child, Adult, Older adult
Study population: Patient with neurodevelopmental diseases and their both parents
Who may be able to join
- Patient (child or adult) presenting neurodevelopmental troubles strongly suspected to suffer from a rare genetic disease (familial or very severe).
- Negative outcome for short read sequencing of the trio (child and parents).
- Informed consent to the study by the patient (if applicable) or their legal representatives if under-aged or under guardianship.
- Patients benefiting from the social security (French health care system).
- Possible recruitment of both parents matching the inclusion criteria.
- Informed consent form signed for their own participation.
- Parents benefiting from the social security (French health care system).
Who cannot join
- Genetic predisposition already identified explaining the disease.
- Paients for which the WGS for the trio has not been performed.
- Patients having withdrawn their consent.
- Pregnant or lactating woman.
- Parents under guardianship or curatorship.
- Parents also presenting a neurodevelopmental deficiency.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Angers University Hospital
Angers, Maine-et-Loire, 49000
Brest University Hospital
Brest, Finistère, 29000
Nantes University Hospital
Nantes, Loire-Atlantique, 44093
Rennes University Hospital
Rennes, Ille-et-Vilaine, 35000
Tours University Hospital
Tours, Indre-et-Loire, 37000
About this study
Patients with neurodevelopmental diseases and their families need to identify the genetic cause of the disease to allow for recognition of the disability, genetic counseling, and possible hope for participation in therapeutic research studies. Access to high-throughput genomic exome or genome analysis allows the identification of a genetic cause for approximately half of the patients. However, families with no result or with a variant of unknown significance after these tests may find themselves in a new diagnostic impasse.
The high-throughput sequencing used today generates sequences of the order of 100 base pairs (so-called "short read" sequencing). This allows an analysis of about 90% of the genome. However, many regions are not accessible in regions of interest for the genetic diagnosis of rare diseases. Long fragment sequencing generates sequences that are about 20 times larger and its use has recently made it possible to sequence the human genome almost completely (https://www.science.org/doi/10.1126/science.abj6987). The main contribution lies in the analysis of complex regions of the genome such as segmental duplications or centromeric regions. It is likely that this technology increases the sensitivity of detection of genetic variants in patients with genetic diseases. Its contribution should be studied in patients for whom no genetic cause has been identified by classical techniques.
This study aim to investigate the contribution of long fragment genome sequencing.
Read the detailed description
Ten families with a child suffering from a neurodevelopmental disease will be recruited by geneticists being part of the CLAD-Ouest. An EDTA blood sample will be taken from the patient and their parents (trio analysis). The blood samples will then be used to extract nucleic acids (DNA).
The blood samples will be sent and centralized to the genetics laboratory of the Nantes University Hospital. The DNA will be extracted and anonymized.
The files generated after DNA sequencing will have as an identification key the anonymization number provided at the time of inclusion of the individual in the study. The raw data and VCF files will be uploaded to the BIRD computing cluster in Nantes, where they will be stored for the duration of the study (2 years). The different university hospitals will then be able to retrieve the data and analyze the variants identified in the patients recruited by their center. A centralized analysis to annotate, filter and interpret the variants will be performed by a group of bioinformaticians and biologists from HUGO (University Hospital from the Grand Ouest). Long-term archiving of the data will be performed at the Nantes University Hospital.
- Keywords
- long read sequencing, rare genetic diseases, neurodevelopmental diseases, diagnostic
- Medical subject headings
- Genetic Diseases, Inborn, Nervous System Diseases, Developmental Disabilities, Growth Disorders, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Participants | Patients with neurodevelopmental disease and their both parents |
What is being measured
The primary outcome is the main question the study is designed to answer.
Use of long read sequencing in patients suffering from a neurodevelopmental disease without pathogenic or probably pathogenic variation identified by short read sequencing
Identification of a genetic diagnosis : detection of one or several variant(s) - nucleotidic, change in copy number, structural variants- of class 4 or 5 (probably pathogenic or pathogenic), explaining the genetic origin of the neurodevelopmental pathology
Measured: through study completion, an average of 2 years
Secondary outcomes (1)
Analysis of the implementation of the long read sequencing of trios (patients and parents)
Measurement of the failing rate of long read sequencing, turn around time between sequencing and results available to clinical team
Measured: through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2022
- Study start19 Dec 2022
- Primary completion8 Mar 2023
- Study completion8 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Genetic DiseaseStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe 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
- Family based
- Time perspective
- Cross-sectional
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Rennes University Hospital, University Hospital, Angers, University Hospital, Brest, University Hospital, Tours
- Responsible party
- Sponsor
- Investigators
- Stéphane BEZIEAU, MD, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05643274
- Sponsor's protocol ID
- RC22_0373
- Acronym
- HiFi-NDD
- Status last verified
- Apr 2024
- First submitted
- 22 Nov 2022
- Last updated
- 24 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Long Read Genome Sequencing in Patients Suffering From Neurodevelopmental Troubles
- ClinicalTrials.gov ID
- NCT05643274
- Acronym / sponsor ID
- HiFi-NDD / RC22_0373
- Keywords
- long read sequencing, rare genetic diseases, neurodevelopmental diseases, diagnostic
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- Rennes University Hospital, University Hospital, Angers, University Hospital, Brest, University Hospital, Tours
- Study start
- 19 Dec 2022 (actual)
- Primary completion
- 8 Mar 2023 (actual)
- Study completion
- 8 Mar 2024 (actual)
- First posted
- 8 Dec 2022 (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.
Patients with neurodevelopmental diseases and their families need to identify the genetic cause of the disease to allow for recognition of the disability, genetic counseling, and possible hope for participation in therapeutic research studies. Access to high-throughput genomic exome or genome analysis allows the identification of a genetic cause for approximately half of the patients. However, families with no result or with a variant of unknown significance after these tests may find themselves in a new diagnostic impasse.
The high-throughput sequencing used today generates sequences of the order of 100 base pairs (so-called "short read" sequencing). This allows an analysis of about 90% of the genome. However, many regions are not accessible in regions of interest for the genetic diagnosis of rare diseases. Long fragment sequencing generates sequences that are about 20 times larger and its use has recently made it possible to sequence the human genome almost completely (https://www.science.org/doi/10.1126/science.abj6987). The main contribution lies in the analysis of complex regions of the genome such as segmental duplications or centromeric regions. It is likely that this technology increases the sensitivity of detection of genetic variants in patients with genetic diseases. Its contribution should be studied in patients for whom no genetic cause has been identified by classical techniques.
This study aim to investigate the contribution of long fragment genome sequencing.
Detailed description
Ten families with a child suffering from a neurodevelopmental disease will be recruited by geneticists being part of the CLAD-Ouest. An EDTA blood sample will be taken from the patient and their parents (trio analysis). The blood samples will then be used to extract nucleic acids (DNA).
The blood samples will be sent and centralized to the genetics laboratory of the Nantes University Hospital. The DNA will be extracted and anonymized.
The files generated after DNA sequencing will have as an identification key the anonymization number provided at the time of inclusion of the individual in the study. The raw data and VCF files will be uploaded to the BIRD computing cluster in Nantes, where they will be stored for the duration of the study (2 years). The different university hospitals will then be able to retrieve the data and analyze the variants identified in the patients recruited by their center. A centralized analysis to annotate, filter and interpret the variants will be performed by a group of bioinformaticians and biologists from HUGO (University Hospital from the Grand Ouest). Long-term archiving of the data will be performed at the Nantes University Hospital.
Study design
- Observational model
- Family based
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants | – | –Patients with neurodevelopmental disease and their both parents |
Who may qualify
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- Patient with neurodevelopmental diseases and their both parents
Key inclusion criteria (7 listed)
- Patient (child or adult) presenting neurodevelopmental troubles strongly suspected to suffer from a rare genetic disease (familial or very severe).
- Negative outcome for short read sequencing of the trio (child and parents).
- Informed consent to the study by the patient (if applicable) or their legal representatives if under-aged or under guardianship.
- Patients benefiting from the social security (French health care system).
- Possible recruitment of both parents matching the inclusion criteria.
Key exclusion criteria (6 listed)
- Genetic predisposition already identified explaining the disease.
- Paients for which the WGS for the trio has not been performed.
- Patients having withdrawn their consent.
- Pregnant or lactating woman.
- Parents under guardianship or curatorship.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Use of long read sequencing in patients suffering from a neurodevelopmental disease without pathogenic or probably pathogenic variation identified by short read sequencing
Time frame: through study completion, an average of 2 years
Identification of a genetic diagnosis : detection of one or several variant(s) - nucleotidic, change in copy number, structural variants- of class 4 or 5 (probably pathogenic or pathogenic), explaining the genetic origin of the neurodevelopmental pathology
1 secondary outcome
Analysis of the implementation of the long read sequencing of trios (patients and parents)
Time frame: through study completion, an average of 2 years
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 24 Apr 2024.
- Individual participant dataSharing planned: Undecided
Related trials for Genetic Disease
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
RecruitingPhase 1/2
A First-in-human Study of KK8123 in Adults With X-linked Hypophosphatemia
X-linked Hypophosphatemia
RecruitingObservational study
Blood, Urine, and Tissue Collection for Cutaneous Lymphoma, Eczema, and Atopic Dermatitis Research
Cutaneous T-cell Lymphoma, Sezary Syndrome
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.
Stéphane BEZIEAU, MD principal investigator
Nantes University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Genetic Disease and Neurologic Disorder, run by Nantes University Hospital at 5 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 7 inclusion and 6 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 24 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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?
Use of long read sequencing in patients suffering from a neurodevelopmental disease without pathogenic or probably pathogenic variation identified by short read sequencing (time frame: through study completion, an average of 2 years). 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 24 Apr 2024.