Clinical trial NCT02789059: Muscle Oxygenation in Effort in Neuromuscular Diseases
Official title: Muscle Oxygenation Modification During Effort in 4 Groups of Neuromuscular Diseases Compared to Healthy Controls, and Mitochondrial Function and Phenotype Assessment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Neuromuscular Diseases
Keywords: Becker muscular dystrophy
Facioscapulohumeral dystrophy
congenital myopathy
motor neurone diseases
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2016-06-02
Enrollment: 170
Sex: MALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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

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.

Primary outcomes:
measure: muscle oxygenation
timeFrame: on the day of first evaluation Visit V1
measure: Muscle oxygenation
timeFrame: on the day of first evaluation Visit V1
Secondary outcomes:
measure: maximal isokinetic strength of the knee extensors
timeFrame: on the day of first evaluation Visit V1
measure: Gas exchange
timeFrame: on the day of first evaluation Visit V1
measure: MFM score
timeFrame: on the day of first evaluation Visit V1
measure: 6 Minutes Walking Test (MWT)
timeFrame: on the day of first evaluation Visit V1
measure: Vignos functional scales
timeFrame: on the day of first evaluation Visit V1
measure: Brooke functional scales
timeFrame: on the day of first evaluation Visit V1
measure: Medical Research Council Muscle testing
timeFrame: on the day of first evaluation Visit V1
measure: Mitochondrial phenotype
timeFrame: at V2 at least 1 week after V1
measure: Mitochondrial H2O2 production
timeFrame: at V2 at least 1 week after V1
measure: kinetic of Muscle oxygenation
timeFrame: on the day of first evaluation Visit V1
Other outcomes:
Locations:
city: Amiens
country: France
facility: Hôpital Amiens Nord, Service de Neurologie
city: Lille
country: France
facility: CHRU de Lille, Hôpital Swyngedhauw
city: Reims
country: France
facility: Hôpital Sébastopol, CHU de Reims
Study officials:
affiliation: CHRU de LILLE
name: Vincent Tiffreau, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Allart E, Olivier N, Hovart H, Thevenon A, Tiffreau V. Evaluation of muscle oxygenation by near-infrared spectroscopy in patients with Becker muscular dystrophy. Neuromuscul Disord. 2012 Aug;22(8):720-7. doi: 10.1016/j.nmd.2012.04.011. Epub 2012 Jun 8.