Mitochondrial Disease-associated ImmunoDeficiencies

Mitochondrial Disorders Clinical Trial

— MitoID  

Official title:

Determining the Relevance of Mitochondrial Disease-associated ImmunoDeficiencies - MitoID

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06213103
• Other study ID #: CHUBX 2022/36
• Status: Recruiting
• Start date: January 30, 2024
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: University Hospital, Bordeaux
• Contact: Aurélien TRIMOUILLE, MD
• Phone: +335 57 82 10 49
• Email: aurelien.trimouille[@]chu-bordeaux.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The study aims at characterizing the immune dysfunctions in patients with mitochondrial diseases. This has prognostic and diagnostic interest as well as potential for the discovery of new therapeutic strategies to alleviate disease burden.

Description:

Mitochondrial pathologies are rare genetic diseases, and affect about 1 in 4300 people. These pathologies are characterized by an energetic deficit that can affect all organs, and can manifest from birth to adulthood. The clinical expression is very heterogeneous, the symptoms can include encephalopathies, myopathies, cardiomyopathies, among others, with frequently "an illegitimate association of symptoms" that add up in a progressive way. These pathologies are related to the presence of pathogenic mutations in the genes of the nuclear genome involved in mitochondrial metabolism, or directly in the genes of the mitochondrial DNA (mtDNA). The immune system dysfunctions associated with mitochondrial diseases remain unknown to date despite the presence of the deleterious variant in leukocytes. Recent studies by group of the investigators and others in animal models clearly show the importance of mitochondrial functions in the regulation of inflammatory and antimicrobial processes. These experimental data are particularly relevant in light of recent clinical studies indicating that patients with mitochondriopathies have a higher rate of bacterial infections compared to control individuals. The investigators hypothesized that immunological parameters assessment in patients will reveal new dysfunctions associated with these pathologies and that some of these parameters will be a prognostic factor in these "step-like" progression of these diseases. This study will recruit 30 patients with mitochondrial disorders followed in Bordeaux University Hospital and Toulouse University Hospital for who the mutation of mitochondrial DNA has been previously identified. Among classical disease activity information, blood samples will be collected to study immunological parameters. Translational research will be realized on patient' samples to assess immune cell subsets and innate immune cells functions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years and older

Eligibility

Inclusion Criteria:

• General inclusion criteria:
• Patient weighing more than 30kg
• Person affiliated with or receiving a social security plan;
• Patient-specific inclusion criteria:
• Patient with molecularly proven primary mitochondrial disease
• Free, informed, written consent signed by parental authority holders for minor patients and the investigator prior to any examination required by the research and oral and/or written assent by the participant (depending on age).
• Free, informed consent signed by the patient's representative for adult patients under guardianship and the investigator prior to any examination required by the research.
• Free, informed consent signed by the patient of legal age and the investigator prior to any examination required by the research
• Specific inclusion criteria for controls:
• Person who has been informed of the purpose of the study and person matched in age (+/- 5 years) and sex to a patient with primary mitochondrial disease at the time of sampling
• Free, informed, and signed consent
• Person with no known mitochondrial disease

Exclusion Criteria:

• Pregnant or breastfeeding women
• Refusal to consent to participate in research,
• Patients for whom molecular causes have not been formally identified (genetic analyses not performed, or no variant or variant of unknown significance after analysis).

Related Conditions & MeSH terms

• Mitochondrial Diseases
• Mitochondrial Disorders

Intervention

Procedure:
• Patient cohort
Collection of 6 blood tubes at the inclusion visit.
• Control cohort
Collection of 6 blood tubes at the inclusion visit.

Locations

Country	Name	City	State
France	Chu Bordeaux	Bordeaux
France	Hopital Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunological parameters	Distribution of several quantitative immunological parameters at inclusion. The following parameters will be considered : Immunoglobulins in g/l (IgG subclasses, IgA, IgM)	Inclusion visit
Primary	Immunological parameters	Distribution of several quantitative immunological parameters at inclusion. The following parameters will be considered : multiplex flow cytometry panels (Th1, Th2, Th17, Tfh, T, B, monocytes) in fluorescence intensity unit	Inclusion visit
Secondary	Immunological parameters	Description of the percentage of patients with abnormal immunological parameters	Inclusion visit
Secondary	infectious events	Incidence of severe or recurrent infectious events retrospectively compared to the general population	Inclusion visit
Secondary	Biological markers	Description of the percentage of patients with abnormal key cytokines (TNF, IL-1b, IL-6, IL-12)	Inclusion visit