Unraveling Metabolic Involvement in Facioscapulohumeral Dystrophy Through Metabolomics (METIN-FSHD)

The pathogenesis of facioscapulohumeral dystrophy (FSHD), one of the most prevalent types of inherited muscle disease, is unknown. The reasons underlying its significant clinical heterogeneity, incomplete penetrance, and sex specific differences in the age of onset, are not currently understood. While metabolic changes associated with this disease have so far deserved little attention, recent studies have pinpointed significant metabolic dysregulation as an emerging driving mechanism in the pathophysiology of this untreatable disease. To test this hypothesis, we will perform a deep metabolic phenotyping in a large cohort of highly clinically characterized FSHD patients at different stage of disease and age/sex-matched controls by state-of-art plasma metabolomic and mitochondrial biomarker profiling. These data will allow attributing specific metabolomic signatures to different stages of the disease in each sex. Metabolic pathway analysis will allow gaining insights into the type of metabolic dysregulation associated with the disease pathogenesis, leading to the identification of targeted metabolic/nutritional interventions and biomarker discovery.

Study Overview

• Status: Not yet recruiting
• Conditions: Facioscapulohumeral Muscular Dystrophy
• Intervention / Treatment: Other: metabolomic on plasma sample

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Marco Spinazzi, MD, PhD; Phone Number: +33 (0)2 41 35 51 19; Email: Marco.Spinazzi@chu-angers.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Recruitment of participants will be conducted at Centre Hospitalier Universitaire d'Angers. All subjects will be clinically evaluated on the basis of the CCEF evaluation protocol. Informed consent will be obtained according to the declaration of Helsinki by each participant after explanations on the research protocol and scientific aims.

Patients will be excluded when they have other disorders that will influence the measurements. Age- and sex-matched healthy subjects will be included through specific calls depending on age.

Description

Inclusion Criteria:

• participant fasting for at least 8 h at the time of blood sampling
• patient with a molecular diagnosis of FSHD (know number of D4Z4 contractions)
• patient with a typical FSHD presentation (at least facial, pelvic ans scapular girdles signs)
• patient with a preserved ability to ambulate at the time of the selection (use of a cane is allowed)

Exclusion Criteria:

• Severe cardiac and respiratory dysfunction.
• Presence of severe systemic diseases unrelated to FSHD.
• Presence of uncontrolled diabetes or hypothyroidism.
• Alcohol or toxic abuse.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
cases; patients with molecular diagnosis of facioscapulohumeral dystrophy	Other: metabolomic on plasma sample; metabolic phenotyping by plasma metabolomic and mitochondrial biomarker profiling
controls; healthy volunteers	Other: metabolomic on plasma sample; metabolic phenotyping by plasma metabolomic and mitochondrial biomarker profiling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
metabolic profiling	to perform a detailed metabolic profiling by state-of-art plasma metabolomic coupled to the analysis of GDF15 and FGF21, two recently established biomarkers of mitochondrial dysfunction, in symptomatic FSHD patients of different clinical severity compared to controls	results should be obtained within 3 months following the inclusion of the last participant

Collaborators and Investigators

• Sponsor: University Hospital, Angers
• Collaborators: Federico II University; University of Modena and Reggio Emilia

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: October 11, 2023
• First Submitted That Met QC Criteria: October 11, 2023
• First Posted (Actual): October 17, 2023

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Facioscapulohumeral
• Other Study ID Numbers: 49RC23_0340

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No