Pro-inflammatory Cytokines in Facioscapulohumeral Muscular Dystrophy (CYTOKINE-FSH) (CYTOKINE-FSH)
Primary Purpose
Muscular Dystrophies
Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
cytokines dosage
test of walk
Manual muscular test
Motrice fonction mesurement
Sponsored by
About this trial
This is an interventional other trial for Muscular Dystrophies
Eligibility Criteria
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
Sites / Locations
- CHU de NICE
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Facioscapulohumeral muscular dystrophy
Arm Description
Adult ambulant patients with facioscapulohumeral muscular dystrophy type 1 (FSHD1)
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
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
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
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)
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
Full Information
NCT ID
NCT04694456
First Posted
December 31, 2020
Last Updated
January 5, 2021
Sponsor
Centre Hospitalier Universitaire de Nice
1. Study Identification
Unique Protocol Identification Number
NCT04694456
Brief Title
Pro-inflammatory Cytokines in Facioscapulohumeral Muscular Dystrophy (CYTOKINE-FSH)
Acronym
CYTOKINE-FSH
Official Title
Pro-inflammatory Cytokines as Potential Therapeutic Target in Type 1 Facioscapulohumeral Muscular Dystrophy: Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 30, 2018 (Actual)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
March 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophies
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Interventional pilot study
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Facioscapulohumeral muscular dystrophy
Arm Type
Experimental
Arm Description
Adult ambulant patients with facioscapulohumeral muscular dystrophy type 1 (FSHD1)
Intervention Type
Other
Intervention Name(s)
cytokines dosage
Other Intervention Name(s)
biological analysis
Intervention Description
Mesure of cytokines concentration in serum
Intervention Type
Procedure
Intervention Name(s)
test of walk
Intervention Description
patient must walk during 6 minutes on a flat surface
Intervention Type
Procedure
Intervention Name(s)
Manual muscular test
Intervention Description
test performed to evaluate the patient muscular weakness
Intervention Type
Procedure
Intervention Name(s)
Motrice fonction mesurement
Intervention Description
scale allowing the evaluation of patient posture and upper body movements
Primary Outcome Measure Information:
Title
Comparison of serum IL-6 levels between FSHD1 patients and control subjects (from other previous studies) comparable in terms of age and sex
Description
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)
Time Frame
21 months
Secondary Outcome Measure Information:
Title
Comparison of serum levels of 28 oher pro-inflammatory cytokines between FSHD1 patients and control subjects
Description
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
Time Frame
21 months
Title
Comparison of cytokines produced upon in vitro stimulation of blood cells in FSHD1 patients and control subjects
Description
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
Time Frame
21 months
Title
Evaluation of potential correlations between cytokines levels (either in the serum or produced upon in vitro stimulation) and clinical severity in FSHD1 patients
Description
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)
Time Frame
21 months
Title
Evaluation of potential correlations between cytokines levels (either in the serum or produced upon in vitro stimulation) and muscle MRI caracteristics in FSHD1 patients
Description
Whole body MRI will be recorded (T1 and T2STIR sequences) in order to evaluate muscle oedema, inflammation and degeneration
Time Frame
21 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
CHU de NICE
City
Nice
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
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Pro-inflammatory Cytokines in Facioscapulohumeral Muscular Dystrophy (CYTOKINE-FSH)
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