Muscle Oxygenation in Effort in Neuromuscular Diseases

Study Overview
=================
Brief Summary
-----------------
Previous studies showed modifications of muscle oxygenation parameters in muscular dystrophies du to an impairment or an absence of dystrophin. Our study aim at assessing muscle oxygenation during effort in different neuromuscular diseases (muscular dystrophies related and not related to dystrophin, non dystrophic myopathies and motor neuron diseases) compared to a group of healthy controls. Patients and controls are invited to perform an inframaximal , standardized effort of the knee extensors by the mean of an isokinetic dynamometer. Muscle oxygenation parameters are assessed through a Near Infrared Spectroscopy (NIRS) Device. In patients affected by dystrophin related myopathies, a muscle biopsy will be performed in order to analyse mitochondrial oxygenation parameters and mitochondrial phenotype. Our Hypothesis is that muscle oxygenation is impaired in dystrophin related muscular dystrophies compared to other neuromuscular diseases and healthy controls because of lack of muscle capillary vessels dilatation during effort and impairment of mitochondrial function.

Detailed Description
-----------------
This study is a prospective physiological study in a pathological condition (neuromuscular diseases). 5 groups of voluntary participants will be investigated: 1. 20 subjects affected by Dystrophin related muscular dystrophy (Becker Muscular Dystrophy ) 2. Subjects affected by muscular dystrophy not related to dystrophin impairment : 20 subjects affected by facioscapulohumeral dystrophy and 20 subjects affected by Limb Girdle Muscular dystrophy 3. 20 subjects affected by non-dystrophic myopathies (Congenital myopathies ) 4. 20 subjects affected by motor diseases: amyotrophic lateral sclerosis(ALS), Charcot Marie Tooth disease, Spinal Muscular Atrophy . 5. 20 healthy controls Objective: asses the muscular oxygenation modifications during a standardized effort and compare the variables between groups. Analyze the mitochondrial function and phenotype in the BMD group compared to healthy controls Outcome : Muscle Oxygenation by Near Infrared Spectroscopy parameters; oxygen consumption, Muscle Function Measure, Vignos and Brooke score, Borg scale, 6 minutes walk test, mitochondrial phenotype, mitochondrial oxygenation 3 visits : 1- inclusion 2- standardized effort protocol 3- for Becker dystrophy patients and voluntary controls, muscle biopsy of the Vastus Lateralis

Official Title
-----------------
Muscle Oxygenation Modification During Effort in 4 Groups of Neuromuscular Diseases Compared to Healthy Controls, and Mitochondrial Function and Phenotype Assessment

Conditions
-----------------
Neuromuscular Diseases

Intervention / Treatment
-----------------
* Other: muscle oxygenation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: healthy subjects and subjects affected by one of the fallowing neuromuscular diseases: Becker Muscular dystrophy Facioscapulohumeral dystrophy, Limb Girdle Muscular Dystrophy , Congenital Myopathy , Spinal Muscular Atrophy Charcot Marie Tooth Disease and Amyotrophic Lateral Sclerosis , able to walk presenting a manual muscle testing of at Least 4/5 on the quadriceps according to the Medical research Council Exclusion Criteria: musculoskeletal pain of the quadriceps other neurological disorders Heart failure arrhythmia, uncontrolled hypertension, angina pectoris dyspnoea >2 according to the NYHA Peripheral artery disease BMI >30kg.m-2.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: muscle oxygenation<br>assesment of muscle oxygenation and gas exchanges | Other: muscle oxygenation<br>* Subjects will be invited to perform an isokinetic effort of the knee extensors against an isokinetic dynamometer. During this effort, muscle oxygenation and oxygen consumption will be assessed with a near infrared spectroscopy device and a gas exchange measurement device. Patients affected by Becker muscular dystrophy and healthy controls will be invited to have a muscle biopsy of the vastus lateralis.<br>* Other names: Muscle biopsy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| muscle oxygenation | level of deoxyhemoglobin assessed with the NIRS device during the isokinetic effort of the knee extensors | on the day of first evaluation Visit V1 | 
| Muscle oxygenation | kinetics of the deoxyhemoglobin assessed with the NIRS device during the isokinetic effort of the knee extensors | on the day of first evaluation Visit V1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximal isokinetic strength of the knee extensors | measurements of the maximal moment during a maximal effort of the knee extensors with an isokinetic dynamometer | on the day of first evaluation Visit V1 | 
| Gas exchange | measurements of O2 and CO2 exchanges during the isokinetic effort | on the day of first evaluation Visit V1 | 
| MFM score | Motor Function Measure score (in %) assessment. quantitative scale that makes it possible to measure the functional motor abilities of a person affected by a neuromuscular disease. | on the day of first evaluation Visit V1 | 
| 6 Minutes Walking Test (MWT) | assessment of the time performed during a 6 minutes walking test | on the day of first evaluation Visit V1 | 
| Vignos functional scales | assesment of the 1 to 6 Vignos score for the lower limb functional assesment | on the day of first evaluation Visit V1 | 
| Brooke functional scales | the 1 to 10 Brooke score for upper limb functional assesment | on the day of first evaluation Visit V1 | 
| Medical Research Council Muscle testing | Assesment of the Medical Research Council 1 to 5 Muscle testing score of the quadriceps muscles | on the day of first evaluation Visit V1 | 
| Mitochondrial phenotype | Mitochondrial respiration (O2 consumption) of muscle fibers of the vastus lateralis | at V2 at least 1 week after V1 | 
| Mitochondrial H2O2 production | Mitochondrial H2O2 production of muscle fibers of the vastus lateralis | at V2 at least 1 week after V1 | 
| kinetic of Muscle oxygenation | kinetic of level of deoxyhemoglobin during the isokinetic effort of the extensors of the knee | on the day of first evaluation Visit V1 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Becker muscular dystrophy, Facioscapulohumeral dystrophy, congenital myopathy, motor neurone diseases