Pro-inflammatory Cytokines in Facioscapulohumeral Muscular Dystrophy (CYTOKINE-FSH) (CYTOKINE-FSH)

Pro-inflammatory Cytokines as Potential Therapeutic Target in Type 1 Facioscapulohumeral Muscular Dystrophy: Pilot Study

The facial-glenohumeral muscular dystrophy type 1 (DMFSH1) is characterized by a selective and asymmetrical involvement of the facial muscles, the shoulder girdle and the anterolateral lodge legs. Genetically, the disease is transmitted in an autosomal dominant manner and is caused by a pathogen contraction of repeat units (UR) say D4Z4 localized to the telomeric portion of chromosome 4qA. The loss of UR causes hypomethylation of DNA and chromatin relaxation of the region that lead to inappropriate expression of DUX4 retrogene highly toxic. The inappropriate expression induces a T cell reaction inflammatory response that participate and increase muscle damage. In favor of this hypothesis, several muscle MRI studies have shown that atrophy and fibro-adipose degeneration (hyper signal in T1) were preceded by the appearance of muscle inflammation (hyper signal T2STIR) confirmed on histologically and dysregulation of genes involved in adaptive and innate immunity. scientific hypothesis and potential benefits: the investigateur hypothesize that in patients of DMFSH1, the immune system cells may participate in the pathophysiology of the disease through changes in serum secretion of one or more cytokines and / or a modification of the response of inflammatory cells in some cell damage stimuli. Design: this is a single-center pilot study, interventional. In this study, the investigator will assay the serum cytokines and changes in peripheral blood cells of the expression of cytokines in response to some stimuli in 20 patients with Type 1 DMFSH genetically confirmed at an intermediate stage of clinical disease (kept walking, but at least one muscle of lower limbs reached) and compare with controls from the CYTOKINAGE study. The investigator will also carry patients clinical testing (MMT sum score) and functional (6minute test march MFM) and a MRI not injected whole body (T1 sequences + and T2STIR) to study the relationship between these parameters and secretion cytokines or serum in response to certain stimuli Main objective: to compare serum levels of IL-6 in patients with DMFSH and controls.

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophies
• Intervention / Treatment: Other: cytokines dosage; Procedure: test of walk; Procedure: Manual muscular test; Procedure: Motrice fonction mesurement

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France
    • CHU de Nice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• male or female age 18 to 75
• suffering from genetically confirmed FSHD1 (<11 D4Z4 repeat units on permissive chromosome 4 allele)
• ambulant or walking with assistance
• Manual Muscle Testing ≥4 for 1 of lower limb muscles

Exclusion Criteria:

• pregnancy or breast feeding
• stay in tropical/subtropical country within 3 months
• physical exercice within 10 hours
• specific diet (e.g. hypocaloric or cholesterol lowering diet)
• regular alcohol consumption; drug consumption within 3 months
• immunosuppressive or immonumodulating drug within 2 weeks or for more than 3 months withing last 6 months
• vaccination, blood transfusion of immunoglobulin treatment within 3 months
• infection within 3 weeks; HIV, HBV, HCV seropositivity
• chronic inflammatory and/or autoimmune or allergic disease from the gut (Crohn disease, ulcerative colitis), skin (psoriasis, atopic dermatitis), joints (rhumatoid arthritis), nervous system (multiple sclerosis), diabetes type I and II
• neurodegenerative disorders (Alzheimer's or Parkinson's diseases)
• diagnosed cancer not under remission for at least 5 years
• participation in the last 3 months in a research clinical trial with exposure to a pharmaceutical product or a medical device
• muscular MRI contraindication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Facioscapulohumeral muscular dystrophy; Adult ambulant patients with facioscapulohumeral muscular dystrophy type 1 (FSHD1)	Other: cytokines dosage; Mesure of cytokines concentration in serum; Other Names: biological analysis; Procedure: test of walk; patient must walk during 6 minutes on a flat surface; Procedure: Manual muscular test; test performed to evaluate the patient muscular weakness; Procedure: Motrice fonction mesurement; scale allowing the evaluation of patient posture and upper body movements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of serum IL-6 levels between FSHD1 patients and control subjects (from other previous studies) comparable in terms of age and sex	Serum IL-6 levels will be measured using v-plex technology (MSD) in FSHD1 patients and compared with results obtained in paired control subjects from 2 cohorts (NCT00998231 and Cytokinage study NCT02660723)	21 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of serum levels of 28 oher pro-inflammatory cytokines between FSHD1 patients and control subjects	Serum levels of 28 other cytokines will be measured using v-plex technology (MSD) in FSHD1 patients and compared with results obtained in paired control subjects	21 months
Comparison of cytokines produced upon in vitro stimulation of blood cells in FSHD1 patients and control subjects	Cytokine production will be induced in blood cells by non-specific stimulation with LPS, ATP+LPS-EB or poly (I:C) in FSHD1 patients and compared with results obtained in control subjects	21 months
Evaluation of potential correlations between cytokines levels (either in the serum or produced upon in vitro stimulation) and clinical severity in FSHD1 patients	Clinical severity and muscle impairment will be evaluated using standardized clinical scales (Manual Muscle Testing, Motor Function Measure-32, 6-minute walk test, age-corrected Clinical Severity Score)	21 months
Evaluation of potential correlations between cytokines levels (either in the serum or produced upon in vitro stimulation) and muscle MRI caracteristics in FSHD1 patients	Whole body MRI will be recorded (T1 and T2STIR sequences) in order to evaluate muscle oedema, inflammation and degeneration	21 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2018
• Primary Completion (Actual): May 18, 2021
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: December 31, 2020
• First Submitted That Met QC Criteria: December 31, 2020
• First Posted (Actual): January 5, 2021

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 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: 16-AOI-13

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