Muscle Oxygenation in Effort in Neuromuscular Diseases (OXYNEMU)

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

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.

Study Overview

• Status: Unknown
• Conditions: Neuromuscular Diseases
• Intervention / Treatment: Other: muscle oxygenation

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

• Study Type: Interventional
• Enrollment (Anticipated): 170
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vincent Tiffreau, MD; Email: vincent.tiffereau@CHRU-LILLE.FR
• Study Contact Backup: Name: Nicolas Olivier, PhD; Email: nicolas.olivier@univ-lille2.fr

Study Locations

• France
  • Amiens, France
    • Not yet recruiting
    • Hôpital Amiens Nord, Service de Neurologie
    • Contact: Philippe MERLE, MD,PhD; Email: merle.philippe@chu-amiens.fr
    • Principal Investigator: Philippe MERLE, MD,PhD
  • Lille, France
    • Recruiting
    • CHRU de Lille, Hôpital Swyngedhauw
    • Contact: Vincent TIFFEREAU, MD; Email: vincent.tiffreau@chru-lille.fr
  • Reims, France
    • Not yet recruiting
    • Hôpital Sébastopol, CHU de Reims
    • Contact: François BOYER, MD,PhD; Email: fboyer@chu-reims.fr
    • Principal Investigator: François BOYER, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: muscle oxygenation; assesment of muscle oxygenation and gas exchanges

Other: muscle oxygenation; 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.; 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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Principal Investigator: Vincent Tiffreau, MD, CHRU de Lille

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 2, 2015
• Primary Completion (ANTICIPATED): July 1, 2017
• Study Completion (ANTICIPATED): July 1, 2017

Study Registration Dates

• First Submitted: May 24, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (ESTIMATE): June 2, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Becker muscular dystrophy; congenital myopathy; Facioscapulohumeral dystrophy; motor neurone diseases
• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases
• Other Study ID Numbers: 2013_29; 2014-A01157-40 (OTHER: ID RCB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED