Chronic Fatigue Etiology and Recovery in Covid-19 Patients: the Role of Fatigability (FatCovid-19)

Chronic Fatigue Etiology and Recovery in Covid-19 Patients : the Role of Fatigability and Stay in Intensive Care

Chronic fatigue is the most common and debilitating symptom in intensive care unit (ICU) survivors. Indeed, it has been widely reported that patients who stayed in ICU for prolonged periods report a feeling of tiredness for months to years after ICU discharge. This symptom seems particularly pronounced in Covid-19 patients and may affect 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 the feeling of fatigue of Covid-19 patients. 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 and its recovery will allow to optimize rehabilitation treatments to shorten the persistence of chronic fatigue and in fine improve life quality.

Study Overview

• Status: Recruiting
• Conditions: Chronic Fatigue Syndrome; Intensive Care Unit; Muscle
• Intervention / Treatment: Other: Questionnaires; Biological: blood test; Other: Maximal effort test; Device: actigraphy; Device: Neuromuscular evaluation; Other: stool analysis; Other: food diary

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jérome MOREL, MD PhD; Phone Number: +33 0477828553; Email: jerome.morel@chu-st-etienne.fr

Study Locations

• France
  • Grenoble, France
    • Not yet recruiting
    • CHU de Grenoble
    • Contact: Pierre BOUZAT, MD PhD
    • Principal Investigator: Pierre BOUZAT, MD PhD
    • Sub-Investigator: Renaud TAMISIER, MD PhD
    • Sub-Investigator: Stéphane DOUTRELEAU, MD PhD
  • Lyon, France
    • Not yet recruiting
    • Clinique de la Sauvegarde - Lyon
    • Contact: Olivier DESEBBE, MD
    • Principal Investigator: Olivier DESEBBE, MD
  • Lyon, France
    • Not yet recruiting
    • Hôpital Croix Rousse - HCL
    • Contact: Céline GUICHON, MD
    • Sub-Investigator: Céline GUICHON, MD
    • Sub-Investigator: Mélanie PRUDENT, MD
    • Sub-Investigator: Emeric STAUFFER, MD
  • Pierre-benite, France, 69310
    • Recruiting
    • Centre Hospitalier de Lyon Sud
    • Contact: Sébastien COURAUD, MD PhD
    • Principal Investigator: Sébastien COURAUD, MD PhD
  • Saint Etienne, France, 42055
    • Recruiting
    • CHU Saint-etienne
    • Sub-Investigator: Pascal GIRAUX, MD
    • Sub-Investigator: Lydia OUJAMAA, MD
    • Sub-Investigator: Marine Sorg, MD
    • Sub-Investigator: Léonard FEASSON, MD PhD
    • Sub-Investigator: Clément Foschia, MD
    • Sub-Investigator: Pierre CROISILLE, MD PhD
    • Contact: Jérome MOREL, MD PhD; Phone Number: +33 (0)477828553; Email: jerome.morel@chu-st-etienne.fr
    • Principal Investigator: Jérôme MOREL, MD PhD
    • Principal Investigator: Guillaume THIERY, MD PhD
  • Saint Etienne, France, 42100
    • Not yet recruiting
    • Clinique Mutualiste Saint Etienne
    • Contact: Vincent GAUTHIER, MD
    • Principal Investigator: Vincent GAUTHIER, MD
  • Saint-Genis-Laval, France, 69230
    • Recruiting
    • Hôpital Henry Gabrielle
    • Contact: Sophie JACQUIN-COURTOIS, MD PhD
    • Principal Investigator: Sophie JACQUIN-COURTOIS, MD PhD
  • Saint-Étienne, France, 42000
    • Not yet recruiting
    • Hôpital privé de la Loire
    • Principal Investigator: Laurent GERGELE, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for patients who have been in intensive care :

• Diagnosed with Covid-19
• Ventilated in ICU for at least 3 consecutive days
• ICU discharge between 4 and 8 weeks
• Approval received from a physician
• Command of the French language

Inclusion Criteria for patients who have NOT been in intensive care :

• Diagnosed with Covid-19 : positive serological test or positive PCR test following nasopharyngeal swabbing
• Approval received from a physician
• Command of the French language

Exclusion Criteria:

• Taking neuroactive substances that can alter corticospinal excitability
• Patients with co-morbidities leading to significant fatigue: e.g. cancerous pathologies, sleep apnea
• Patients with neurodegenerative or neuromuscular disease
• Contraindication to the application of a magnetic field
• Contraindication to the practice of Magnetic Resonance Imaging
• Participant is pregnant
• Patients with psychiatric disorders
• Paraplegic and hemiplegic patients
• Addictive disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: "Non-fatigued" patients who have been in intensive care units	Other: Questionnaires; Quality of life Depression Physical pain Social provisions Quality of sleep; Biological: blood test; complete blood count and cytokine concentration, TNF-alpha, LDL oxidized, AOPP, SOD, GPX, catalase, albumin, transthyretin, RBP, transferin, α-1 glycoprotein acide, ferritine, selenium, zinc, magnesium; Other: Maximal effort test; The maximal effort test with VO2max recordings will be assessed during the first visit to the laboratory.; Device: actigraphy; assessment of sleep quality; Device: Neuromuscular evaluation; The maximum isometric force produced by the knee extensors will be measured on the ergometer; the intensity of muscular electrical activity recorded by surface electromyography; Peripheral nerve stimulation; Transcranial magnetic stimulation; Magnetic resonance imaging; Other: stool analysis; analyze the composition of the intestinal microbiote. concerns only the patients of Saint Etienne; Other: food diary; 3 days of information to determine nutrient intakes. concerns only the patients of Saint Etienne
Experimental: "Fatigued" patients who have been in intensive care units	Other: Questionnaires; Quality of life Depression Physical pain Social provisions Quality of sleep; Biological: blood test; complete blood count and cytokine concentration, TNF-alpha, LDL oxidized, AOPP, SOD, GPX, catalase, albumin, transthyretin, RBP, transferin, α-1 glycoprotein acide, ferritine, selenium, zinc, magnesium; Other: Maximal effort test; The maximal effort test with VO2max recordings will be assessed during the first visit to the laboratory.; Device: actigraphy; assessment of sleep quality; Device: Neuromuscular evaluation; The maximum isometric force produced by the knee extensors will be measured on the ergometer; the intensity of muscular electrical activity recorded by surface electromyography; Peripheral nerve stimulation; Transcranial magnetic stimulation; Magnetic resonance imaging; Other: stool analysis; analyze the composition of the intestinal microbiote. concerns only the patients of Saint Etienne; Other: food diary; 3 days of information to determine nutrient intakes. concerns only the patients of Saint Etienne
Experimental: patients who have not been in intensive care units	Other: Questionnaires; Quality of life Depression Physical pain Social provisions Quality of sleep; Biological: blood test; complete blood count and cytokine concentration, TNF-alpha, LDL oxidized, AOPP, SOD, GPX, catalase, albumin, transthyretin, RBP, transferin, α-1 glycoprotein acide, ferritine, selenium, zinc, magnesium; Other: Maximal effort test; The maximal effort test with VO2max recordings will be assessed during the first visit to the laboratory.; Device: actigraphy; assessment of sleep quality; Device: Neuromuscular evaluation; The maximum isometric force produced by the knee extensors will be measured on the ergometer; the intensity of muscular electrical activity recorded by surface electromyography; Peripheral nerve stimulation; Transcranial magnetic stimulation; Magnetic resonance imaging; Other: stool analysis; analyze the composition of the intestinal microbiote. concerns only the patients of Saint Etienne; Other: food diary; 3 days of information to determine nutrient intakes. concerns only the patients of Saint Etienne

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
voluntary maximum force reduction	6 weeks post-discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuromuscular function : cortical activity	Level of cortical activation and cortico-spinal excitability measured by transcranial magnetic stimulation	6 weeks post-discharge
Neuromuscular function : Peripheral function	Peripheral function by electrical nerve stimulation	6 weeks post-discharge
Maximal oxygen uptake (VO2max)	measured by effort test	6 weeks post-discharge
quality of sleep	measured by actigraphy	6 weeks post-discharge
muscle volume	with Magnetic resonance imaging	6 weeks post-discharge
metabolic fatigue	measured by a Phosphorus 31 Nuclear magnetic resonance test	6 weeks post-discharge
microbiote intestinal	stool analysis (concerns only the patients of Saint Etienne)	baseline and 6 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: University of Saint-Etienne; Laboratoire des Adaptations Métaboliques à l'Exercice en conditions Physiologiques et Pathologiques
• Investigators: Principal Investigator: Jérome MOREL, MD PhD, CHU de Saint Etienne

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Neuromuscular function; Fatigability
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Disease Attributes; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Chronic Disease; Neuroinflammatory Diseases; Fatigue; Fatigue Syndrome, Chronic
• Other Study ID Numbers: 20CH085; 2020-A00982-37 (Other Identifier: ANSM)

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