Mitochondrial Disease-associated ImmunoDeficiencies

Recruiting

• Conditions: Mitochondrial Disorders
• Interventions: Procedure: Patient cohort; Procedure: Control cohort

• Registration Number: NCT06213103
• Lead Sponsor: University Hospital, Bordeaux

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2023-06-09
• Study First Submitted QC: 2024-01-16
• Study First Posted: 2024-01-19
• Study Start: 2024-01-30
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-02
• Last Update Posted: 2024-02-05
• Primary Completion: 2025-01
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
o Patient cohort	Patient cohort	Patient with moleculary proven mitochondrial disorder
o Control cohort	Control cohort	People without moleculary proven mitochondrial disorder

Primary Outcome Measures

Name	Time	Method
Immunological parameters	Inclusion visit	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

Secondary Outcome Measures

Name	Time	Method
infectious events	Inclusion visit	Incidence of severe or recurrent infectious events retrospectively compared to the general population
Biological markers	Inclusion visit	Description of the percentage of patients with abnormal key cytokines (TNF, IL-1b, IL-6, IL-12)
Immunological parameters	Inclusion visit	Description of the percentage of patients with abnormal immunological parameters

Trial Locations

Locations (2)

Chu Bordeaux; 🇫🇷 Bordeaux, France

Hopital Toulouse; 🇫🇷 Toulouse, France