Mitochondrial DiseasesMITOMICSNCT04920812
MITOMICS : a Multi-OMICS Approach for the Diagnosis of Mitochondrial Diseases
An observational study of Mitochondrial Diseases, run by Centre Hospitalier Universitaire de Nice at 9 sites in France.
Trial summary
MITOMICS aims to determine which RNA-Seq results (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. Analysis of RNA-Seq and WES results will performed with a computational approach using an autoencoder-based method Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Mitochondrial Diseases
- What is being tested?
- diagnosis of mitochondrial myopathy
- How many people
- 66 participants
- Where
- 9 sitesFrance
- Study dates
- 7 Mar 2022to 7 Sep 2025
- Phase
- Observational
- 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
Study population: Patients are seen in consultation by the genetic doctors of the different centers as part of the usual management of their mitochondrial disease.
Who may be able to join
- Patients suspected of a mitochondrial disease with muscular signs (clinical, histological or biochemical)
- Patients with negative mtDNA and WES NGS in trio
- Patients with routine muscle and skin biopsies available
- Blood samples from parents and / or relatives available for segregation studies
- Informed consent of the study signed by the patient or the legal representatives of the minor patient or under guardianship
- Patients affiliated to social security
Who cannot join
- Patients with suspected mitochondrial disease without muscle involvement
- Patients for whom the mtDNA NGS and WES have not been performed
- Patients with suspected mitochondrial disease with causal variant identified
- Refusal to sign the informed consent for the study
- Insufficient amount of frozen material or culture failure for fibroblasts
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
France9 sites, 9 recruiting
- Recruiting
chu Angers
Angers
Vincent PROCACCIO, MD
- Not yet recruiting
C.H.R.U. Brest
Brest, France
Jean Noury, MD
- Not yet recruiting
Chu Brest
Brest
Pascale Marcorelles, Professor
- Recruiting
APHM
Marseille
Shahram ATTARIAN, MD
BRIGITTE CHABROL, Md
- Recruiting
APHM
Marseille
Shahram ATTARIAN, Professor
- Recruiting
Chu Montpellier
Montpellier
Cecilia MARELLI, Doctor
- Recruiting
Chu de Nantes
Nantes, France
Sandra Mercier, MD
- Not yet recruiting
CHU Nantes
Nantes
Yann PEREON, Professor
Yann PEREON, Professor
- Recruiting
CHU de Nice
Nice, CHU de NICE, 06003
0492034702, bannwarth.s@chu-nice.fr
Sylvie BANNWARTH, Professor
About this study
Official title: Interest of Multi-omics (WES / RNA-Seq) Approach to Fight Against the Diagnostic Deadlock in Mitochondrial Diseases
MITOMICS aims to determine which RNA-Seq results (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. Analysis of RNA-Seq and WES results will performed with a computational approach using an autoencoder-based method
Read the detailed description
Mitochondrial diseases (MD) are rare, clinically and genetically extremely heterogeneous, caused by a deficit of energy production via the mitochondria. Mitochondria are dependent on 2 genomes mitochondrial DNA and nuclear DNA, and many pathogenic variants carried by these 2 genomes are responsible for mitochondrial diseases. The diagnostic strategies for MD patients have evolved significantly with the emergence of Next Generation Sequencing (NGS) also accelerating the identification of the responsible gene. However, the diagnostic yield remains limited and requires the development of new approaches. Previous studies showed that WES and RNA-Seq combination improves the diagnosis of MD, essentially by helping in the interpretation of identified VUS.
With MITOMICS project, we will included 66 patients suspected of a mitochondrial myopathy (clinical, histological or biochemical), with a negative mtDNA and WES NGS in trio. For each patient we will sequenced RNA from muscle and fibroblasts. Using a new innovative methology of multi-OMICS integration we will determined which RNA-Seq data (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. The results obtained will allow the interpretation of VUS and the identification of specific molecular signatures.
- Conditions
- Mitochondrial Diseases
- Being tested
- diagnosis of mitochondrial myopathy
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
diagnosis of mitochondrial myopathyGenetic
- Determination of the presence of specific molecular signatures at the RNA level in muscles and fibroblasts from patients
| Study group | Role | What they receive |
|---|---|---|
| Mitochondrial diseases | annalysing with methology of multi-OMICS integration we will determined which RNA-Seq data (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. Receives: Genetic: diagnosis of mitochondrial myopathy |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of variations interpreted as responsible for the Mitochondrial diseases
- Comparison of the number of variations (splicing variant, expression level) or VUS, identified in WES, interpreted as responsible for the disease (class 4 or 5 variants) thanks to the RNA-Seq carried out at from a muscle biopsy or RNA-Seq performed from fibroblasts
Measured: baseline
Secondary outcomes (3)
RNA in mitochondiral deseases
Patients for whom the RNA-Seq could not be performed and reason for failure
Measured: baseline
variation of RNA in mitochondiral deseases
Variations identified by RNA-Seq, allowing interpretation of WES data (splicing aberrants, monoallelic expressions, etc.)
Measured: baseline
specific molecular signatures of mitochondiral deseases
Determination of the presence of specific molecular signatures at the RNA level in muscles and fibroblasts from patients
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start7 Mar 2022
- Primary completion7 Mar 2022
- Study completion7 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe 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
- Cohort
- Time perspective
- Other
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- SYLVIE BANNWARTH, Principal investigator, Centre Hospitalier Universitaire de Nice
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04920812
- Sponsor's protocol ID
- 19-API-01
- Other IDs
- 2020-A02651-38
- Acronym
- MITOMICS
- Status last verified
- Feb 2025
- First submitted
- 4 Jun 2021
- Last updated
- 25 Feb 2025
- 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 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interest of Multi-omics (WES / RNA-Seq) Approach to Fight Against the Diagnostic Deadlock in Mitochondrial Diseases
- ClinicalTrials.gov ID
- NCT04920812
- Acronym / sponsor ID
- MITOMICS / 19-API-01
- Conditions
- Mitochondrial Diseases
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 7 Mar 2022 (actual)
- Primary completion
- 7 Mar 2022 (actual)
- Study completion
- 7 Sep 2025 (estimated)
- First posted
- 10 Jun 2021 (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.
MITOMICS aims to determine which RNA-Seq results (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. Analysis of RNA-Seq and WES results will performed with a computational approach using an autoencoder-based method
Detailed description
Mitochondrial diseases (MD) are rare, clinically and genetically extremely heterogeneous, caused by a deficit of energy production via the mitochondria. Mitochondria are dependent on 2 genomes mitochondrial DNA and nuclear DNA, and many pathogenic variants carried by these 2 genomes are responsible for mitochondrial diseases. The diagnostic strategies for MD patients have evolved significantly with the emergence of Next Generation Sequencing (NGS) also accelerating the identification of the responsible gene. However, the diagnostic yield remains limited and requires the development of new approaches. Previous studies showed that WES and RNA-Seq combination improves the diagnosis of MD, essentially by helping in the interpretation of identified VUS.
With MITOMICS project, we will included 66 patients suspected of a mitochondrial myopathy (clinical, histological or biochemical), with a negative mtDNA and WES NGS in trio. For each patient we will sequenced RNA from muscle and fibroblasts. Using a new innovative methology of multi-OMICS integration we will determined which RNA-Seq data (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. The results obtained will allow the interpretation of VUS and the identification of specific molecular signatures.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mitochondrial diseases | – | Genetic: diagnosis of mitochondrial myopathyannalysing with methology of multi-OMICS integration we will determined which RNA-Seq data (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients are seen in consultation by the genetic doctors of the different centers as part of the usual management of their mitochondrial disease.
Key inclusion criteria (6 listed)
- Patients suspected of a mitochondrial disease with muscular signs (clinical, histological or biochemical)
- Patients with negative mtDNA and WES NGS in trio
- Patients with routine muscle and skin biopsies available
- Blood samples from parents and / or relatives available for segregation studies
- Informed consent of the study signed by the patient or the legal representatives of the minor patient or under guardianship
Key exclusion criteria (5 listed)
- Patients with suspected mitochondrial disease without muscle involvement
- Patients for whom the mtDNA NGS and WES have not been performed
- Patients with suspected mitochondrial disease with causal variant identified
- Refusal to sign the informed consent for the study
- Insufficient amount of frozen material or culture failure for fibroblasts
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 |
|---|---|---|
| diagnosis of mitochondrial myopathy• Determination of the presence of specific molecular signatures at the RNA level in muscles and fibroblasts from patients | Genetic | Mitochondrial diseases |
Primary outcome
number of variations interpreted as responsible for the Mitochondrial diseases
Time frame: baseline
• Comparison of the number of variations (splicing variant, expression level) or VUS, identified in WES, interpreted as responsible for the disease (class 4 or 5 variants) thanks to the RNA-Seq carried out at from a muscle biopsy or RNA-Seq performed from fibroblasts
3 secondary outcomes
RNA in mitochondiral deseases
Time frame: baseline
variation of RNA in mitochondiral deseases
Time frame: baseline
specific molecular signatures of mitochondiral deseases
Time frame: baseline
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 25 Feb 2025.
- 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.
SYLVIE BANNWARTH principal investigator
Centre Hospitalier Universitaire de Nice
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mitochondrial Diseases, run by Centre Hospitalier Universitaire de Nice at 9 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 6 inclusion and 5 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 25 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 9 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 SYLVIE BANNWARTH (0492034702, bannwarth.s@chu-nice.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of variations interpreted as responsible for the Mitochondrial diseases (time frame: baseline). 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 25 Feb 2025.