Rare Genetic Muscle DiseasesARNseq-MuscNCT06833489
Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
A study testing ARN extraction from muscle biopsies in people with Rare Genetic Muscle Diseases and Muscular Dystrophy, Duchenne, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
Since 2017, more than 250 analyses performed at the Molecular Genetics Laboratory of the Timone Enfant Hospital have yielded negative results in patients with rare genetic muscle diseases. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Rare Genetic Muscle Diseases, Muscular Dystrophy, Duchenne, Muscular Dystrophy, Becker
- What is being tested?
- ARN extraction from muscle biopsies
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- 1 Mar 2025to 1 Mar 2027
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- patients with rare genetic muscle diseases who have benefited from high-throughput sequencing analysis (panel of 200 genes defined by the FILNEMUS Rare Neuromuscular Disease Network) carried out at the Molecular Genetics Laboratory, Medical Genetics Department, Timone Enfant Hospital since 2017.
- This criterion is necessary to limit the analysis to patients with muscular diseases among all the patients analysed by the Molecular Genetics Laboratory.
- this genetic analysis did not identify pathogenic variants explaining the patient's phenotype This criterion is necessary in order to include only patients in diagnostic error.
- a muscle biopsy of the patient is available in the Biological Resources Centre (CRB) at the AP-HM.
Who cannot join
- Patients with no muscle biopsy available in the CRB.
- Patients with an established molecular diagnosis.
- Patients for whom RNA extraction from a muscle biopsy sample did not yield RNA of sufficient quality (INR >7) will be excluded from the study. A maximum of two extraction attempts will be performed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hopital Timone
Marseille, 13005
Svetlana GOROKHOVA Dr, +33491381927, promotion.interne@ap-hm.fr
About this study
Since 2017, more than 250 analyses performed at the Molecular Genetics Laboratory of the Timone Enfant Hospital have yielded negative results in patients with rare genetic muscle diseases. The researchers hypothesise that some of these misdiagnosed patients carry pathogenic RNA (transcript) disrupting variants that were not identified by DNA sequencing. In fact, DNA sequencing analyses can be negative despite the presence of a pathogenic variant that disrupts RNA splicing or expression, causing a genetic disease. For this reason, RNA sequencing can provide a diagnosis in patients who have not been diagnosed by DNA sequencing, thus putting an end to diagnostic wandering. Thus, as a descriptive prevalence study, the objectives are first to determine the rate of positive diagnoses made by the RNAseq approach in patients with muscle diseases that have not yet been diagnosed, and then to identify the genomic characteristics of the pathogenic variants identified in patients by RNAseq analysis, in order to facilitate the identification of this type of variant in future patients.
50 patients will be included in this study during 2 years.
- Conditions
- Rare Genetic Muscle Diseases, Muscular Dystrophy, Duchenne, Muscular Dystrophy, Becker, Congenital Myopathy, Pompe Disease (Infantile-Onset)
- Being tested
- ARN extraction from muscle biopsies
- Medical subject headings
- Muscular Dystrophy, Duchenne, Myotonia Congenita, Glycogen Storage Disease Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARN extraction from muscle biopsiesOther
There will be no visits from participants, so we will be using samples already in the Biological Resources Centre (CRB).
RNA will be extracted from muscle biopsies taken as part of the treatment. RNAseq libraries will be sequenced by the Genomics and Bioinformatics Platform (GBiM) at Marseille Medical Genetics (MMG, U1251, AMU). Sequencing will be performed in paired-end (2*100 bp) on Illumina's Novaseq 6000 system (50 million clusters per sample, 100 M paired-end reads) and then analysed by bioinformatics.
| Study group | Role | What they receive |
|---|---|---|
| Sequencing of RNAseq libraries | Experimental | There will be no visits from participants, so we will be using samples already in the Biological Resources Centre (CRB).
RNA will be extracted from muscle biopsies taken as part of the treatment. RNAseq libraries will be sequenced by the Genomics and Bioinformatics Platform (GBiM) at Marseille Medical Genetics (MMG, U1251, AMU). Sequencing will be performed in paired-end (2*100 bp) on Illumina's Novaseq 6000 system (50 million clusters per sample, 100 M paired-end reads) and then analysed by bioinformatics. Receives: Other: ARN extraction from muscle biopsies |
What is being measured
The primary outcome is the main question the study is designed to answer.
rate of positive diagnoses using the RNAseq approach
to determine the rate of positive diagnoses made using the RNAseq approach in patients with muscle diseases who have not yet been diagnosed. A patient is considered to be in diagnostic limbo if DNA sequencing of 200 genes responsible for muscle diseases has not identified pathogenic variants responsible for the patient's phenotype. Investigators are going to use transcriptomic analysis (RNA sequencing) in combination with innovative bioinformatics tools to identify variants with a deleterious effect at RNA level in patients with undiagnosed muscle diseases. This will make it possible to establish a molecular diagnosis and put an end to misdiagnosis in many patients.
Measured: From enrollment to the end of study at 24 months
Secondary outcomes (1)
Identification of genomic characteristics
identify the genomic characteristics of pathogenic variants identified by the RNAseq approach. This analysis could potentially uncover certain characteristics that are specific to this type of variant, making it possible to suggest their presence in other undiagnosed patients in the future.
Measured: From enrollment to end of study at 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2025
- Study start1 Mar 2025 (estimated)
- Primary completion1 Sep 2026 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rare Genetic Muscle 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06833489
- Sponsor's protocol ID
- RCAPHM22_0420
- Other IDs
- 2024-A01079-38
- Acronym
- ARNseq-Musc
- Status last verified
- Feb 2025
- First submitted
- 13 Feb 2025
- Last updated
- 18 Feb 2025
- 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 18 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
- ClinicalTrials.gov ID
- NCT06833489
- Acronym / sponsor ID
- ARNseq-Musc / RCAPHM22_0420
- Conditions
- Rare Genetic Muscle Diseases, Muscular Dystrophy, Duchenne, Muscular Dystrophy, Becker, Congenital Myopathy, Pompe Disease (Infantile-Onset)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 18 Feb 2025 (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.
Since 2017, more than 250 analyses performed at the Molecular Genetics Laboratory of the Timone Enfant Hospital have yielded negative results in patients with rare genetic muscle diseases. The researchers hypothesise that some of these misdiagnosed patients carry pathogenic RNA (transcript) disrupting variants that were not identified by DNA sequencing. In fact, DNA sequencing analyses can be negative despite the presence of a pathogenic variant that disrupts RNA splicing or expression, causing a genetic disease. For this reason, RNA sequencing can provide a diagnosis in patients who have not been diagnosed by DNA sequencing, thus putting an end to diagnostic wandering. Thus, as a descriptive prevalence study, the objectives are first to determine the rate of positive diagnoses made by the RNAseq approach in patients with muscle diseases that have not yet been diagnosed, and then to identify the genomic characteristics of the pathogenic variants identified in patients by RNAseq analysis, in order to facilitate the identification of this type of variant in future patients.
50 patients will be included in this study during 2 years.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sequencing of RNAseq libraries | Experimental | Other: ARN extraction from muscle biopsiesThere will be no visits from participants, so we will be using samples already in the Biological Resources Centre (CRB). RNA will be extracted from muscle biopsies taken as part of the treatment. RNAseq libraries will be sequenced by the Genomics and Bioinformatics Platform (GBiM) at Marseille Medical Genetics (MMG, U1251, AMU). Sequencing will be performed in paired-end (2*100 bp) on Illumina's Novaseq 6000 system (50 million clusters per sample, 100 M paired-end reads) and then analysed by bioinformatics. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- patients with rare genetic muscle diseases who have benefited from high-throughput sequencing analysis (panel of 200 genes defined by the FILNEMUS Rare Neuromuscular Disease Network) carried out at the Molecular Genetics Laboratory, Medical Genetics Department, Timone Enfant Hospital since 2017.
- This criterion is necessary to limit the analysis to patients with muscular diseases among all the patients analysed by the Molecular Genetics Laboratory.
- this genetic analysis did not identify pathogenic variants explaining the patient's phenotype This criterion is necessary in order to include only patients in diagnostic error.
- a muscle biopsy of the patient is available in the Biological Resources Centre (CRB) at the AP-HM.
Key exclusion criteria (3 listed)
- Patients with no muscle biopsy available in the CRB.
- Patients with an established molecular diagnosis.
- Patients for whom RNA extraction from a muscle biopsy sample did not yield RNA of sufficient quality (INR >7) will be excluded from the study. A maximum of two extraction attempts will be performed.
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 |
|---|---|---|
| ARN extraction from muscle biopsiesThere will be no visits from participants, so we will be using samples already in the Biological Resources Centre (CRB). RNA will be extracted from muscle biopsies taken as part of the treatment. RNAseq libraries will be sequenced by the Genomics and Bioinformatics Platform (GBiM) at Marseille Medical Genetics (MMG, U1251, AMU). Sequencing will be performed in paired-end (2*100 bp) on Illumina's Novaseq 6000 system (50 million clusters per sample, 100 M paired-end reads) and then analysed by bioinformatics. | Other | Sequencing of RNAseq libraries |
Primary outcome
rate of positive diagnoses using the RNAseq approach
Time frame: From enrollment to the end of study at 24 months
to determine the rate of positive diagnoses made using the RNAseq approach in patients with muscle diseases who have not yet been diagnosed. A patient is considered to be in diagnostic limbo if DNA sequencing of 200 genes responsible for muscle diseases has not identified pathogenic variants responsible for the patient's phenotype. Investigators are going to use transcriptomic analysis (RNA sequencing) in combination with innovative bioinformatics tools to identify variants with a deleterious effect at RNA level in patients with undiagnosed muscle diseases. This will make it possible to establish a molecular diagnosis and put an end to misdiagnosis in many patients.
1 secondary outcome
Identification of genomic characteristics
Time frame: From enrollment to end of study at 24 months
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 18 Feb 2025.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ARN extraction from muscle biopsies in people with Rare Genetic Muscle Diseases and Muscular Dystrophy, Duchenne, run by Assistance Publique Hopitaux De Marseille 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 4 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: looking for participants now, as of the sponsor's last update on 18 Feb 2025. 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?
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 Svetlana GOROKHOVA Dr (+33491381927, promotion.interne@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
rate of positive diagnoses using the RNAseq approach (time frame: From enrollment to the end of study at 24 months). 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 18 Feb 2025.