Can Fatigability Neuromuscular Explain Chronic Fatigue in People With Multiple Sclerosis?

Phase 2

Terminated

• Conditions: Sclerosis, Multiple
• Interventions: Other: Evaluation of degree chronic fatigue.; Other: Questionnaires; Biological: Blood sample; Device: Capacity of muscular oxygen extraction; Other: Cardiopulmonary evaluation; Device: Sleep assessment; Device: Metabolic fatigue; Other: Neuromuscular evaluation

• Registration Number: NCT03983720
• Lead Sponsor: Centre Hospitalier Universitaire de Saint Etienne

Brief Summary

Chronic fatigue is the most common and debilitating symptom in multiple sclerosis patients. This chronic fatigue affects their quality of life by decreasing their capacity to perform simple tasks of daily life.

The aim of the present project is to determine whether deteriorated neuromuscular function (i.e. increased fatigability) is involved in this feeling of chronic fatigue. Because the causes of this feeling are multi-dimensional, a large battery of tests will allow us to better understand the origin of chronic fatigue. A better knowledge of chronic fatigue etiology will allow to optimize rehabilitation treatments to decrease the apparition/persistence of chronic fatigue and in fine improve quality of life.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-06-07
• Study First Submitted QC: 2019-06-11
• Study First Posted: 2019-06-12
• Study Start: 2020-01-21
• Primary Completion: 2021-06-16
• Study Completion: 2021-07-31
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-31
• Last Update Posted: 2023-11-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 67

Inclusion Criteria

For Patients:

• Aged ≥ 18 and ≤ 70 years
• Men or women
• With multiple sclerosis since 2 and 25 years
• Affiliates or beneficiaries of social security scheme
• Signed consent

For Healthy volunteers:

• Aged ≥ 18 and ≤ 70 years
• Men or women
• Matched in accordance with age, sex and level of physical activity

Exclusion Criteria

For Patients and Healthy volunteers:

• High heart rate resting
• Blood pressure > 144/94 mmHg
• Recent adjustment of drug or drug can have an impact on fatigue or stimulant for fatigue
• Taking neuroactive substances that can alter corticospinal excitability
• Contraindication at application magnetic field
• Contraindication at Magnetic Resonance Imaging (MRI)
• Currently participating in a structured exercise program
• Pregnant

For Patients only:

• Spasticity or cerebellar ataxia
• Abnormal range of motion (toe and/or ankle)
• Musculoskeletal injuries that impedes pedaling
• Appearance of symptoms of multiple sclerosis in the 90 days preceding the study

For Healthy volunteers:

• Neurological diseases, cardiovascular, musculoskeletal

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy subjects	Capacity of muscular oxygen extraction	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Evaluation of degree chronic fatigue.	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Blood sample	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Cardiopulmonary evaluation	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Sleep assessment	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Metabolic fatigue	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Questionnaires	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Metabolic fatigue	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Healthy subjects	Questionnaires	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Healthy subjects	Neuromuscular evaluation	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Evaluation of degree chronic fatigue.	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Capacity of muscular oxygen extraction	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and lowly fatigued	Neuromuscular evaluation	Patient with multiple sclerosis and lowly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Cardiopulmonary evaluation	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Sleep assessment	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Healthy subjects	Blood sample	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Healthy subjects	Sleep assessment	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Questionnaires	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Blood sample	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Capacity of muscular oxygen extraction	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Patient with multiple sclerosis and highly fatigued	Neuromuscular evaluation	Patient with multiple sclerosis and highly fatigued will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Healthy subjects	Cardiopulmonary evaluation	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue
Healthy subjects	Metabolic fatigue	Healthy subjects will be included. They will have: Visit 1 (day 0) = Questionnaires, blood sample, cardiopulmonary evaluation, capacity of muscular oxygen extraction, sleep assessment Visit 2 (day 15) = Neuromuscular evaluation Visit 3 (day 30) = Metabolic fatigue

Primary Outcome Measures

Name	Time	Method
Voluntary maximum contraction	Day : 30	Comparison the percentage of decrease in voluntary maximum contraction reported after the fatiguing task. Measured by an instrumented measuring pedal (PowerForce pedal, Model PF1.0.0.0, Radlabor GmbH, Freiburg, Germany)

Secondary Outcome Measures

Name	Time	Method
VO2 max	Day : 30	Measured by effort test
Anemia	Day : 30	Measured by blood count in blood sample
Thermoregulation	Day : 30	Measured by digestible thermometric pill (e-celcius Performance)
Muscle oxygen extraction capacity	Day : 30	Measured by near-infrared spectroscopy (NIRS)
Heart rate	Day : 30	Measured by heart rate monitor
Neuromuscular function during the dynamic strenuous exercise	Day : 30	Cortical activity by transcranial magnetic stimulation, evaluated by recording of the evoked motor potentials; .
Metabolic fatigue	Day : 30	Measured by a Phosphorus 31 Nuclear Magnetic Resonance test
Inflammation	Day : 30	Measured by C-reactiv protein in blood sample
Cognitive fatigue	Day : 30	Measured by Symbol Digit Modalities Test
Sleep quality	Day : 30	Measured by actigraphy
Perceived fatigue	Day : 30	Measured by Borg scale
Muscle volume	Day : 30	Measured by Magnetic Resonance Imaging

Trial Locations

Locations (1)

Chu Saint-Etienne; 🇫🇷 Saint-Étienne, France