NHPMM: Natural History in Primary Mitochondrial Myopathies

Sponsor

Cristina Domínguez González (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05653544

Collaborator

(none)

150

Enrollment

Location

Anticipated Duration (Months)

6.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a longitudinal study in a cohort of patients with a genetic diagnosis of Primary Mitochondrial Myopathy to describe the natural history of the disease and identify clinical, biochemical, molecular, and radiological variables that allow evaluation of the severity and progression of the disease and may be useful in future clinical trials.

Condition or Disease	Intervention/Treatment	Phase
Primary Mitochondrial Myopathies

Detailed Description

Mitochondrial Diseases (MD) are among the most frequent inherited metabolic diseases. Despite their high impact on patients, there are still no authorized drugs capable of modifying their clinical course. MD are clinically and genetically heterogeneous disorders, with muscular symptoms being one of their main manifestations. When muscular symptoms predominate, the disorder is classified as a Primary Mitochondrial Myopathy. In recent years, there have been significant advances in developing potential new treatments in this field. However, the absence of natural history studies makes the design and interpretation of clinical trials difficult and leads to long delays or even failures in the development of new treatments. The investigators propose to characterize in-depth a cohort of patients with Primary Mitochondrial Disorders due to mutations in the mitochondrial DNA (mtDNA) or in genes located in the nuclear genome (nDNA), from a clinical perspective but also a radiological, biochemical, and molecular point of view, and carry out a longitudinal follow-up of these parameters to identify those that are better correlated with severity and that allow to measure changes in the patient's clinical situation. With this objective, the investigators will analyze clinical variables (evaluation of motor function through manual force exploration, functional scales and timed test, quality of life scales, serum biomarkers (GDF15 and FGF21), levels of heteroplasmy for cases harbouring mtDNA mutations and mtDNA copy-number, and muscle magnetic resonance image of the lower extremities with quantification of fat replacement. All parameters will be evaluated at the beginning of the study and then annually during two years of follow-up.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

150 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Natural History and Longitudinal Clinical Assessments in a Spanish Cohort of Primary Mitochondrial Myopathies

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Jan 1, 2025

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Mitochondrial myopathy Mitochondrial myopathy, confirmed genetically

Outcome Measures

Primary Outcome Measures

Motor Function (endurance) [36 months]
6MWT

Secondary Outcome Measures

Motor Function (functional scale) [36 months]
NSAA
Biomarkers [36 months]
Analysis of levels of GDF15 y FGF21 annually
Levels of heteroplasmy [36 months]
Analysis of levels of heteroplasmy annually
Muscle MRI [36 months]
Quantification of the fat fraction in muscle MRI, annually

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Muscle symptoms: exercise intolerance and fatigue, myalgia, recurrent rhabdomyolysis, chronic progressive external ophthalmoplegia and/or muscular weakness
Primary mtDNA mutation or pathogenic mutations in nDNA, especially in genes related to mtDNA maintenance such as TK2, POLG, TWNK and RRM2B, among others.