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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jean-Philippe CAMDESSANCHE, MD PhD; Phone Number: +33 (0)477120559; Email: j.philippe.camdessanche@chu-st-etienne.fr
• Study Contact Backup: Name: Amandine BAUDOT, CRA; Phone Number: +33 (0)477829450; Email: Amandine.Baudot@chu-st-etienne.fr

Study Locations

• France
  • Saint-Étienne, France
    • CHU Saint-Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient with multiple sclerosis and lowly fatigued; 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	Other: Evaluation of degree chronic fatigue.; Evaluation of degree chronic fatigue with the results of survey Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). This result will allow to divide patients in groups : lowly fatigued and highly fatigued.; Other: Questionnaires; Fatigue Severity Scale (FSS); Modified Fatigue Impact Scale (MFIS); Godin Leisure-Time Exercise Questionnaire (GLTEQ); Scale of life quality of multiple sclerosis (SEP-59); Center for Epidemiologic Studies Depression (CES-D); Pittsburgh Sleep Quality Index (PSQ-I); Biological: Blood sample; Blood sample will be realized to evaluate anemia and inflammations.; Other: Cardiopulmonary evaluation; Cardiopulmonary evaluation will be realized with a cycle ergometer.; Device: Capacity of muscular oxygen extraction; Measure the capacity of muscular oxygen extraction with a cycle ergometer.; Device: Sleep assessment; Sleep assessment will be measured by actigraphy during 15 days.; Device: Metabolic fatigue; Metabolic fatigue will be measured by Magnetic Resonance Imaging (MRI).; Other: Neuromuscular evaluation; Neuromuscular evaluation will be measured by the composite of the results of: Fatigue test; Measure of voluntary isometric force; Surface electromyography; Peripheral nerve stimulation; Transcranial Magnetic Stimulation (TMS); Perceived fatigue; Cognitive fatigue; Thermoregulation
Experimental: Patient with multiple sclerosis and highly fatigued; 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	Other: Evaluation of degree chronic fatigue.; Evaluation of degree chronic fatigue with the results of survey Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). This result will allow to divide patients in groups : lowly fatigued and highly fatigued.; Other: Questionnaires; Fatigue Severity Scale (FSS); Modified Fatigue Impact Scale (MFIS); Godin Leisure-Time Exercise Questionnaire (GLTEQ); Scale of life quality of multiple sclerosis (SEP-59); Center for Epidemiologic Studies Depression (CES-D); Pittsburgh Sleep Quality Index (PSQ-I); Biological: Blood sample; Blood sample will be realized to evaluate anemia and inflammations.; Other: Cardiopulmonary evaluation; Cardiopulmonary evaluation will be realized with a cycle ergometer.; Device: Capacity of muscular oxygen extraction; Measure the capacity of muscular oxygen extraction with a cycle ergometer.; Device: Sleep assessment; Sleep assessment will be measured by actigraphy during 15 days.; Device: Metabolic fatigue; Metabolic fatigue will be measured by Magnetic Resonance Imaging (MRI).; Other: Neuromuscular evaluation; Neuromuscular evaluation will be measured by the composite of the results of: Fatigue test; Measure of voluntary isometric force; Surface electromyography; Peripheral nerve stimulation; Transcranial Magnetic Stimulation (TMS); Perceived fatigue; Cognitive fatigue; Thermoregulation
Active Comparator: Healthy subjects; 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	Other: Questionnaires; Fatigue Severity Scale (FSS); Modified Fatigue Impact Scale (MFIS); Godin Leisure-Time Exercise Questionnaire (GLTEQ); Scale of life quality of multiple sclerosis (SEP-59); Center for Epidemiologic Studies Depression (CES-D); Pittsburgh Sleep Quality Index (PSQ-I); Biological: Blood sample; Blood sample will be realized to evaluate anemia and inflammations.; Other: Cardiopulmonary evaluation; Cardiopulmonary evaluation will be realized with a cycle ergometer.; Device: Capacity of muscular oxygen extraction; Measure the capacity of muscular oxygen extraction with a cycle ergometer.; Device: Sleep assessment; Sleep assessment will be measured by actigraphy during 15 days.; Device: Metabolic fatigue; Metabolic fatigue will be measured by Magnetic Resonance Imaging (MRI).; Other: Neuromuscular evaluation; Neuromuscular evaluation will be measured by the composite of the results of: Fatigue test; Measure of voluntary isometric force; Surface electromyography; Peripheral nerve stimulation; Transcranial Magnetic Stimulation (TMS); Perceived fatigue; Cognitive fatigue; Thermoregulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Voluntary maximum contraction	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)	Day : 30

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Investigators: Principal Investigator: Jean-Philippe CAMDESSANCHE, MD PhD, CHU de Saint Etienne

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Actual): June 16, 2021
• Study Completion (Actual): July 31, 2021

Study Registration Dates

• First Submitted: June 7, 2019
• First Submitted That Met QC Criteria: June 11, 2019
• First Posted (Actual): June 12, 2019

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Multiple sclerosis; Chronic fatigue; Sleep assessment; Neuromuscular Fatigability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Fatigue
• Other Study ID Numbers: 19CH030; 2019-A00427-50 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No