Development of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis
NCT ID: NCT06083584
Last Updated: 2025-05-20
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
192 participants
OBSERVATIONAL
2023-11-22
2027-05-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Many of these variants of uncertain significance affect splicing. Their impact can be predicted using in silico tools, but only an analysis of the patient's RNA can confirm their pathogenic nature. Currently, the analysis of transcripts is only done a posteriori, when a variant predicted to impact splicing is detected on the patient's DNA. RT-PCR followed by Sanger sequencing then verifies the impact of the splice variants. This method confirmed the impact of certain splice variants in patients. However, this method is time-consuming and requires custom development, and is mutation/gene/patient-dependent. In contrast, high-throughput RNA sequencing (RNA-Seq) simultaneously analyzes the splicing of numerous genes, with a global approach, applicable to all patients. This approach avoids the custom design of primers, which can be biased by the interpretation of splicing predictions, while RNA-Seq systematically captures and sequences all the transcripts. Finally, RNA-Seq provides additional information compared to DNA sequencing such as the detection of exon skipping, intron inclusion, and the creation of fusion transcripts.
In the GTEx project (GTEx Consortium, 2013), expression levels of human genome transcripts were quantified by RNA-Seq. Using these results, the study investigators measured expression of transcripts of known ALS genes in whole blood. Applying a threshold value of 0.5 transcripts per million reads (TPM), 25 of the 30 ALS genes currently analyzed by NGS in routine diagnostics at Nîmes University Hospital could be eligible for a complete analysis by RNA-Seq. None of the French laboratories carrying out genetic analyzes of ALS has yet developed RNA-Seq as a routine diagnostic tool. The study laboratory receives more than 600 requests for genetic diagnosis of ALS patients per year. The aim of this study is therefore to develop a global method for analyzing RNA transcripts of ALS genes to categorize the mutations to improve the diagnostic management of patients.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Genomic Translation for Amyotrophic Lateral Sclerosis Care
NCT02795897
ALS Research Collaborative
NCT06885918
Amyotrophic Lateral Sclerosis (ALS) Families Project
NCT03865420
Study of miRNA Expression Pattern as Diagnostic and Prognostic Biomarker in Amyotrophic Lateral Sclerosis
NCT01992029
PREVENT ALL ALS Study
NCT06581861
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
COHORT
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Positive controls
6 patients already in database. The 6 confirmed splicing mutations are: DCTN1 (NM\_004082.5): c.3209G\>T, OPTN (NM\_001008211.1) : c.1613-7T\>G, FUS (NM\_004960.4) : c.764+8T\>A, GRN (NM\_002087.4): c.835+1G\>A, GRN (NM\_002087.4): c.709-3C\>G, SPG11 (NM\_025137.4): c.3039-5T\>G
RNA sequencing
RNA-Seq (Sureselect XT HS2 RNA) from patient blood sample
Negative controls
30 patients with familial hypercholesterolemia. The absence of splicing anomalies in the SLA genes after confirmation by RT-PCR followed by Sanger sequencing of the absence of anomalies for the 6 variants listed above for each of the 30 individuals.
RNA sequencing
RNA-Seq (Sureselect XT HS2 RNA) from patient blood sample
Exploratory cohort
156 ALS: 20 ALS patients with splice variants predicted to be deleterious by in silico prediction software; 136 panel-analysis-negative ALS patients (priority will be given to familial ALS)
RNA sequencing
RNA-Seq (Sureselect XT HS2 RNA) from patient blood sample
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
RNA sequencing
RNA-Seq (Sureselect XT HS2 RNA) from patient blood sample
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Have given their informed consent for the genetic study and the biobank
* The patient must be a member or beneficiary of a health insurance plan
Exclusion Criteria
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Association pour la Recherche sur la Sclérose Latérale Amyotrophique et autres maladies du motoneurones
UNKNOWN
Centre Hospitalier Universitaire de Nīmes
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Claire Guissart
Role: PRINCIPAL_INVESTIGATOR
CHU de Nimes
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
CHU de Bordeaux
Bordeaux, , France
CHU de Clermont-Ferrand
Clermont-Ferrand, , France
CHU de Lyon
Lyon, , France
La Timone
Marseille, , France
CHU de Montpellier
Montpellier, , France
CHU de Nîmes
Nîmes, , France
CHU de Toulouse
Toulouse, , France
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
NIMAO/LOCAL/2023/CG-01
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.