Muscle Oxygenation in Effort in Neuromuscular Diseases

Neuromuscular Diseases Clinical Trial

— OXYNEMU  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02789059
• Other study ID #: 2013_29
• Secondary ID: 2014-A01157-40
• Status: Recruiting
• Phase: N/A
• First received: May 24, 2016
• Last updated: May 18, 2017
• Start date: July 2, 2015
• Est. completion date: July 2017

Study information

• Verified date: May 2017
• Source: University Hospital, Lille
• Contact: Vincent Tiffreau, MD
• Email: vincent.tiffereau[@]CHRU-LILLE.FR
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: July 2017
• Est. primary completion date: July 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neuromuscular Diseases

Intervention

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.

Locations

Country	Name	City	State
France	Hôpital Amiens Nord, Service de Neurologie	Amiens
France	CHRU de Lille, Hôpital Swyngedhauw	Lille
France	Hôpital Sébastopol, CHU de Reims	Reims

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Lille

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Gas exchange	measurements of O2 and CO2 exchanges during the isokinetic effort	on the day of first evaluation Visit V1
Secondary	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
Secondary	6 Minutes Walking Test (MWT)	assessment of the time performed during a 6 minutes walking test	on the day of first evaluation Visit V1
Secondary	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
Secondary	Brooke functional scales	the 1 to 10 Brooke score for upper limb functional assesment	on the day of first evaluation Visit V1
Secondary	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
Secondary	Mitochondrial phenotype	Mitochondrial respiration (O2 consumption) of muscle fibers of the vastus lateralis	at V2 at least 1 week after V1
Secondary	Mitochondrial H2O2 production	Mitochondrial H2O2 production of muscle fibers of the vastus lateralis	at V2 at least 1 week after V1
Secondary	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