Neurogenetic DiseasesNRGEN-NGS3NCT07665554
Advancing Neurogenetic Diagnoses Through Long-Read Sequencing
A study testing Skin biopsy and blood sampling in people with Neurogenetic Diseases, run by University Hospital, Bordeaux at 2 sites in France.
Trial summary
Nucleotide repeats emerge as one of the most prolific classes of genetic variations. They have the propensity to in-crease in length across generations, and have been implicated in at least 65 known neurological/ neurodevelop-mental and neuromuscular conditions. Read more about this study
- Who is it for?
- Ages 6 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Neurogenetic Diseases
- What is being tested?
- Skin biopsy and blood sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 304 participants
- Where
- 2 sitesFrance
- Study dates
- Sep 2026to Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 6 to 60 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- All participants :
- Participants affiliated with or beneficiaries of a social security scheme
- Participants who speak French
- Participants aged ≥ 6 and ≤ 60 years
- For patients requiring a new sample:
- Free and informed consent, signed by the parents or the holder of parental authority for patients under the age of 18
Show all 29Show fewer
- Free and informed consent, signed by the patient's representative for adults under guardianship
- Free and informed consent, signed by the adult patient
- For diagnosed patients :
- DeoxyriboNucleic Acid (DNA) sample from a subject carrying a nucleotide repeat expansion in one of the selected genes.
- DNA available in sufficient quantity (5-10 µg) or patient agreeing to a blood draw from which DNA will be extracted.
- DNA extraction methods known and validated by the steering committee (see paragraph 7).
- For participants from undiagnosed families :
- o Index cases:
- Patient affected by a neurological disease candidate for these repeats, for which genomic data did not reveal mutations or expansions in known genes.
- Patient whose DNA is already available and whose extraction method is known and validated by the steering committee or patient whose DNA is not available but who agrees to a blood draw.
- Patient willing to undergo a skin biopsy if not previously obtained.
- Patient with no family members affected by any of the neurological diseases candidate for these repeats, i.e., genomic data do not reveal mutations or expansions in known genes.
- Patient from a family in which at least one affected and one unaffected member agree to partici-pate in the study by providing a sample, or whose DNA is already available and extracted using a method known and validated by the steering committee.
- For all related members of undiagnosed families who have agreed to participate:
- Have at least two other family members who have agreed to participate in the study.
- Agree to provide a blood sample or have DNA already available in sufficient quantity and extracted using a method known and validated by the steering committee.
- Patient willing to undergo a skin biopsy if not previously obtained.
- Be affected by a neurological disease candidate for these repeats, for which genomic data did not reveal mutations or expansions in known genes, or be unaffected and have had a neurological examination showing no signs related to any of the neurological diseases candidate for these repeats.
- For controls :
- Participant for whom:
- a consultation is scheduled at CHU Bordeaux for a reason other than a neurological disorder, has agreed to a neurological examination showing no signs of neurological disease, and has agreed to a blood draw and skin biopsy, or
- the samples required for the study are already available in sufficient quantity in the CHU Bordeaux biobank and extracted using a method known and validated by the steering committee, or
- accompanying a patient attending a consultation at CHU Bordeaux, showing no signs of neurologi-cal disease, and agreeing to a blood draw and skin biopsy, or whose samples are already available in sufficient quantity and extracted using a method known and validated by the steering committee.
Who cannot join
- For all participants:
- Refusal to participate in research: Refusal to provide informed consent or opposition to the use of these samples.
- By the parents or the holder of parental authority for patients under the age of 18
- By the patient's representative for adults under guardianship
- By the adult patient This opposition from the patient must be communicated to the site investigator within a maximum of one month after the information note has been sent. If the letter confirming consent is returned due to an incorrect address, the patient will not be included.
- Degraded DNA or average size < 30 kb
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites
CHU Bordeaux - Hôpital Pellegrin
Bordeaux, France, 33076
Cyril GOIZET, PROF, +335 56 79 59 52, cyril.goizet@chu-bordeaux.fr
AP-HP Hôpital Pitié-Salpêtrière
Paris, France, 75013
Eric LEGUERN, PROF, +331 42 16 13 46, eric.leguern@aphp.fr
Eric LEGUERN, PROF
About this study
Official title: NRGEN-NGS3 : Advancing Neurogenetic Diagnoses Through Long-Read Sequencing
Nucleotide repeats emerge as one of the most prolific classes of genetic variations. They have the propensity to in-crease in length across generations, and have been implicated in at least 65 known neurological/ neurodevelop-mental and neuromuscular conditions. Simultaneous analysis of all these nucleotide repeats is now possible through the cutting-edge methodologies recently developed that are the long-read sequencing and the optical genome mapping. Investigator propose to test these methodologies in patients carrying expansions in those repeats and to determine the capacity of these technics to detect novel repeats in patients with no genetic diagnosis yet.
Read the detailed description
Hereditary neurological diseases caused by nucleotide repeat expansions present significant clinical challenges due to overlapping clinical symptoms and extensive genetic diversity, often resulting in complex diagnostic journeys for patients. In addition, current diagnostic approaches rely on sequential genetic analyses of targeted loci across multiple consultations and dispatching samples to various molecular genetic laboratories. The recent advancement of long-read sequencing technology from Oxford Nanopore and of the optical Genome Mapping from Bionano offer promising and innovative avenues for investigating nucleotide repeat expansions.
This project has then 2 main objectives, to enhance the genetic diagnosis of such mutational events and to identify novel candidate genes or repetitive sequences in neurogenetic conditions.
These methodologies will be applied to 120 carriers of established repeat expansions to help better define the threshold and composition of large repeats leveraging the main advantage offered by each technics to allow full analysis of these repeat sequences. In the case of long read sequencing, an enrichment methodology will be used (adaptive sampling). In order to be sure to analyze 120 patients, investigators will recruit 180 patients (90 in each group).
The second objective relies on the fact that a substantial portion of patients still lack a molecular diagnosis in neuro-genetics. Investigator aim to uncover new abnormal repeat expansions using the same technologies in a separate cohort of patients affected by candidate neurological conditions for these repeats, where genomic data have not revealed mutations or expansions in known genes. The consortium will analyze samples from 30 families affected by a candidate neurogenetic condition
- Conditions
- Neurogenetic Diseases
- Being tested
- Skin biopsy, blood sampling
- Keywords
- long read sequencing, genetic diagnosis, cytogenetics, nucletotide repeat expansion, neurogenetic disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Skin biopsyProcedure or surgery
Skin biopsy is a minimally invasive procedure. It will be performed during a follow-up visit.
The skin biopsy is a technically simple procedure performed using a 5-mm diameter punch under local anesthesia. The procedure can be carried out in a consultation room under strict aseptic conditions and takes a total of approximately 15 minutes.The biopsy may be performed at several anatomical sites but is generally carried out on the inner aspect of the arm.
It will be performed by a resident or a senior registrar. The skin biopsy sample is placed in a vial containing physiological saline and sent at room temperature.
blood samplingProcedure or surgery
Blood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation. Pain, redness, or bleeding may occur at the puncture site. If the required samples are not already available, they will be collected.
The maximum volumes collected will be as follows and will represent a total volume of less than two tablespoons (for participants weighing less than 30 kg, only one tube of each type will be collected)
| Study group | Role | What they receive |
|---|---|---|
| Control | Other | Not described Receives: Procedure: Skin biopsy; Procedure: blood sampling |
| Diagnosed family | Other | Not described Receives: Procedure: blood sampling |
| Undiagnosed family | Other | Not described Receives: Procedure: Skin biopsy; Procedure: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnosis by NGS technology
The first primary endpoint is the ability of the proposed Next-Generation Sequencing (NGS) technology to establish the diagnosis of each neurogenetic disease studied, defined as the presence or absence of the disease, in comparison with the currently used reference method (gene-specific Polymerase Chain reaction (PCR)). NGS analysis will be performed blinded to the results previously obtained on the same samples using the reference technique, taking into account the disease under investigation and the number of repeat amplifications.
Measured: Inclusion visit
Molecular diagnosis
Identification a molecular diagnosis in families undergoing a diagnostic odyssey, by demonstrating both the presence of repeat expansions in affected family members and the absence of such expansions in unaffected individuals within the same family.
Measured: Inclusion visit
Secondary outcomes (2)
New complex haplotypes
Identification of new complex haplotypes
Measured: Inclusion visit
Deleterious biological effect
Identification of a deleterious biological effect of one or more newly identified variants in the new gene(s) of inter-est.
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 posted24 Jun 2026
- Study startSep 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurogenetic DiseasesStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 304 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cyril GOIZET, PROF, Principal investigator, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07665554
- Sponsor's protocol ID
- CHUBX 2025/017
- Acronym
- NRGEN-NGS3
- Status last verified
- Jun 2026
- First submitted
- 11 Jun 2026
- Last updated
- 24 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NRGEN-NGS3 : Advancing Neurogenetic Diagnoses Through Long-Read Sequencing
- ClinicalTrials.gov ID
- NCT07665554
- Acronym / sponsor ID
- NRGEN-NGS3 / CHUBX 2025/017
- Conditions
- Neurogenetic Diseases
- Keywords
- long read sequencing, genetic diagnosis, cytogenetics, nucletotide repeat expansion, neurogenetic disease
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 304 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 24 Jun 2026 (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.
Nucleotide repeats emerge as one of the most prolific classes of genetic variations. They have the propensity to in-crease in length across generations, and have been implicated in at least 65 known neurological/ neurodevelop-mental and neuromuscular conditions. Simultaneous analysis of all these nucleotide repeats is now possible through the cutting-edge methodologies recently developed that are the long-read sequencing and the optical genome mapping. Investigator propose to test these methodologies in patients carrying expansions in those repeats and to determine the capacity of these technics to detect novel repeats in patients with no genetic diagnosis yet.
Detailed description
Hereditary neurological diseases caused by nucleotide repeat expansions present significant clinical challenges due to overlapping clinical symptoms and extensive genetic diversity, often resulting in complex diagnostic journeys for patients. In addition, current diagnostic approaches rely on sequential genetic analyses of targeted loci across multiple consultations and dispatching samples to various molecular genetic laboratories. The recent advancement of long-read sequencing technology from Oxford Nanopore and of the optical Genome Mapping from Bionano offer promising and innovative avenues for investigating nucleotide repeat expansions.
This project has then 2 main objectives, to enhance the genetic diagnosis of such mutational events and to identify novel candidate genes or repetitive sequences in neurogenetic conditions.
These methodologies will be applied to 120 carriers of established repeat expansions to help better define the threshold and composition of large repeats leveraging the main advantage offered by each technics to allow full analysis of these repeat sequences. In the case of long read sequencing, an enrichment methodology will be used (adaptive sampling). In order to be sure to analyze 120 patients, investigators will recruit 180 patients (90 in each group).
The second objective relies on the fact that a substantial portion of patients still lack a molecular diagnosis in neuro-genetics. Investigator aim to uncover new abnormal repeat expansions using the same technologies in a separate cohort of patients affected by candidate neurological conditions for these repeats, where genomic data have not revealed mutations or expansions in known genes. The consortium will analyze samples from 30 families affected by a candidate neurogenetic condition
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | Other | Procedure: Skin biopsy, Procedure: blood sampling |
| Diagnosed family | Other | Procedure: blood sampling |
| Undiagnosed family | Other | Procedure: Skin biopsy, Procedure: blood sampling |
Who may qualify
- Ages
- 6 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (29 listed)
- All participants :
- For patients requiring a new sample:
- For diagnosed patients :
- For participants from undiagnosed families :
- For controls :
Key exclusion criteria (6 listed)
- Refusal to participate in research: Refusal to provide informed consent or opposition to the use of these samples.
- By the parents or the holder of parental authority for patients under the age of 18
- By the patient's representative for adults under guardianship
- By the adult patient This opposition from the patient must be communicated to the site investigator within a maximum of one month after the information note has been sent. If the letter confirming consent is returned due to an incorrect address, the patient will not be included.
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 |
|---|---|---|
| Skin biopsySkin biopsy is a minimally invasive procedure. It will be performed during a follow-up visit. The skin biopsy is a technically simple procedure performed using a 5-mm diameter punch under local anesthesia. The procedure can be carried out in a consultation room under strict aseptic conditions and takes a total of approximately 15 minutes.The biopsy may be performed at several anatomical sites but is generally carried out on the inner aspect of the arm. It will be performed by a resident or a senior registrar. The skin biopsy sample is placed in a vial containing physiological saline and sent at room temperature. | Procedure or surgery | Control, Undiagnosed family |
| blood samplingBlood sampling is a routine biological procedure performed under the same conditions as during a follow-up consultation. Pain, redness, or bleeding may occur at the puncture site. If the required samples are not already available, they will be collected. The maximum volumes collected will be as follows and will represent a total volume of less than two tablespoons (for participants weighing less than 30 kg, only one tube of each type will be collected) | Procedure or surgery | Control, Diagnosed family, Undiagnosed family |
Primary outcome
Diagnosis by NGS technology
Time frame: Inclusion visit
The first primary endpoint is the ability of the proposed Next-Generation Sequencing (NGS) technology to establish the diagnosis of each neurogenetic disease studied, defined as the presence or absence of the disease, in comparison with the currently used reference method (gene-specific Polymerase Chain reaction (PCR)). NGS analysis will be performed blinded to the results previously obtained on the same samples using the reference technique, taking into account the disease under investigation and the number of repeat amplifications.
Molecular diagnosis
Time frame: Inclusion visit
Identification a molecular diagnosis in families undergoing a diagnostic odyssey, by demonstrating both the presence of repeat expansions in affected family members and the absence of such expansions in unaffected individuals within the same family.
2 secondary outcomes
New complex haplotypes
Time frame: Inclusion visit
Deleterious biological effect
Time frame: Inclusion visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
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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.
Cyril GOIZET, PROF principal investigator
University Hospital, Bordeaux
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Skin biopsy and blood sampling in people with Neurogenetic Diseases, run by University Hospital, Bordeaux at 2 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 29 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: opening soon, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cyril GOIZET, PROF (+335 56 79 59 52, cyril.goizet@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnosis by NGS technology (time frame: Inclusion visit). 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 24 Jun 2026.