- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04649086
Muscular Rehabilitation by Eccentric Exercise After Severe COVID-19 Infection (CovExc)
Muscular Rehabilitation by Eccentric Exercise After Severe COVID-19 Infection: Research Protocol for Randomized Controlled Trial (CovExc)
With the COVID-19 pandemic, the number of patients to be treated in rehabilitation increased .
Hospitalization for severe infection can induce muscular atrophy and muscular dysfunction that persists for several months and rehabilitation capacities may be exceeded.
Exercises in eccentric mode could be performed, inducing greater muscular hypertrophy, muscle strength, power and speed than concentric exercises.
The goal of this study was to compare functional recovery at 2 months after a training program in eccentric and concentric mode after severe COVID-19.
An effective rehabilitation could help reduce costs and duration of care.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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-
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Clermont-Ferrand, France, 63000
- CHU de Clermont-Ferrand
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Dijon, France, 21000
- CHU de Dijon
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Saint-Étienne, France, 42000
- CHU de Saint-Etienne
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female, 18 to 80 years old
- Diagnosed for SARS-CoV-2 infection (COVID-19) requiring a rehabilitation program at least 1 month after the hospitalization
- Autonomy in daily life activities 1 month after diagnosis
- Able to walk for 6 min (discontinuous walking possible)
- Giving informed written consent to participate in the study
- Health insurance coverage
Exclusion Criteria:
- Cardiovascular or respiratory contraindication to the rehabilitation program
- Difficulty to perform an eccentric exercise on a seated ergometer
- Pregnant or breastfeeding
- Under guardianship, curatorship or deprived of liberty
- Taking antivitamin K anticoagulation (muscle biopsy)
- Refusal to participate
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Eccentric group
The experimental group (eccentric) will perform 5 habituation sessions: the initial power of the exercise will be set to 10 Watts and then increased by 10% each session, depending on the muscle tolerance.
The training power must correspond to 3 times that of the control group to obtain a similar metabolic stimulation and will be adapted according to the pain felt at the end of the session.
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Participants will perform 24 exercises sessions (30 minutes) with cycloergometer in eccentric mode (while resisting against self-paced pedaling), inducing a greater muscular hypertrophy as compared with concentric mode, the mechanical stimulation being 3 to 4 times greater at the same level metabolic stimulation.
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Active Comparator: Concentric group
The control group (concentric) will perform exercise training at an intensity of 60% of the reserve heart rate determined during an initial cardiorespiratory test.
The power will be adjusted weekly to stay within the target heart rate range.
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The control group (concentric) will perform exercise training at an intensity of 60% of the reserve heart rate determined during an initial cardiorespiratory test.
The power will be adjusted weekly to stay within the target heart rate range.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional walking capacity
Time Frame: Day 0, Month 1, Month 2 and Month 6
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Average change from baseline walking capacity measured by the 6-minutes walk test (6MWT), expressed in meters.
All patients will be asked to cover the longest distance over a 30-meters distance in 6 min with or without stopping and with standardized verbal encouragements according to standard recommendations; to take into account a learning effect, the test will be performed twice, with the longer distance retained, expressed in meters.
To prevent adverse effect, pulsed oxygen saturation (% of pSO²) and heart rate (heartbeat per minute) will be monitored continuously throughout the test by using a digital oximeter.
|
Day 0, Month 1, Month 2 and Month 6
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluating of lower extremity functioning by Short Physical Performance Battery (SPPB) score
Time Frame: Day 0, Month 2 and Month 6
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this test consists of assessing balance in a standing position, lifting from a chair (5 stand to-sit repetitions) and measuring 4-m walking speed (20).
The patient walks 4 m at a normal and comfortable speed.
The "test zone" (4 m) is preceded by an "acceleration zone" (1 m) and is followed by a "deceleration zone" (1 m).
The assessor starts and stops the timing when the subject's foot meets the ground when entering and leaving the "test area", respectively.
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Day 0, Month 2 and Month 6
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Evaluating the maximum muscle strength of the quadriceps by Quadriceps Isometric Maximum Strength (QIMS) test
Time Frame: Day 0, Month 2
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maximum muscle strength of the quadriceps, on the dominant limb, will be measured on a bench: - Strength during isometric contraction (at 90° knee flexion) - Standardized position with the arms crossed on the chest, the absence of back support during the measurement and the maintenance of the hips and the contralateral leg to avoid any compensating movement Three reproducible measurements (±10%) will be taken at 1-min intervals, with the highest value retained.
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Day 0, Month 2
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Evaluating the fatigability of the quadriceps by Quadriceps Intermittent Fatigue (QIF) test
Time Frame: Day 0, Month 2
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this test consists of performing 10 knee extensions at 10% QIMS, then gradually increasing the load (10% by 10%) until exhaustion (cannot perform the movement 2 consecutive times).
The value retained is the last level (% QIMS) performed.
|
Day 0, Month 2
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Evaluating the global fatigability by Modified Fatigue Impact Scale (MFIS)
Time Frame: Day 0, Month 2 and Month 6
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this scale explores cognitive (10 items), physical (9 items) and psychosocial (2 items) fatigue.
The MFIS included 21 items with a total score ranging from 0 to 84 with higher scores indicating a greater impact of quality of life.
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Day 0, Month 2 and Month 6
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Evaluating functional capacities with EuroQol - 5 Dimensions (EQ-5D) questionnaire
Time Frame: Day 0, Month 2 and Month 6
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This questionnaire explores 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
The EQ-5D-5L included 5 items independently scored from 1 to 5 (higher scores indicating a greater impact)and a 0-100 visual analogic scale exploring general health (0 means the worst heath patient can imagine, 100 means the best health patient can imagine).
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Day 0, Month 2 and Month 6
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Evaluating the handgrip strength by standard handgrip strength test
Time Frame: Day 0, Month 2
|
measurement is in 90° elbow flexion, wrist in neutral position.
Three reproducible measurements (± 10%) will be taken at 1-min intervals, with the highest value retained.
|
Day 0, Month 2
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Metabolomic Profile
Time Frame: Day 0, Month 2 (post-training)
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Plasma metabolome profile assessed by variation of number of blood metabolites.
Changes from baseline to post-training intervention in plasma metabolome profile will be compared between excentric and concentric exercise groups.
|
Day 0, Month 2 (post-training)
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Cross sectional area measurement
Time Frame: Day 0, Month 2 (post-training)
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Biopsy from the Vastus lateralis will be performed and the variation of cross sectional area measurement of muscle fibers (µm2) will be analysed and compared between excentric and concentric exercise groups from baseline to post-training intervention.
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Day 0, Month 2 (post-training)
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Capillary to fibre ratio.
Time Frame: Day 0, Month 2 (post-training)
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Biopsy from the Vastus lateralis will be performed and the capillarization (variation of capillary to fiber ratio) will be analysed. Muscle adapations from baseline to post-training intervention will be compared between excentric and concentric exercise groups. |
Day 0, Month 2 (post-training)
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Satellite cell number
Time Frame: Day 0, Month 2 (post-training)
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Biopsy from the Vastus lateralis will be performed and the evolution of number of satellite cell per muscle fiber will be analysed and compared between excentric and concentric exercise groups from baseline to post-training intervention.
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Day 0, Month 2 (post-training)
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Neuromuscular activation
Time Frame: Day 0, Month 2 (post-training)
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Electrophsyiological stimulation of the quadriceps for the measurement of the neuromuscular activation before, during and after the QIF test.
During this test, we measure maximal M-wave, contraction time and torque and the percentage of neuromuscular activation.
Neuromuscular activation will be analysed and compared between excentric and concentric exercise groups from baseline to post-training intervention.
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Day 0, Month 2 (post-training)
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Quadriceps muscular Oxygen Tissue Saturation
Time Frame: Day 0, Month 2 (post-training)
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An infrared spectroscopy device is localized on the anterior part of the quadriceps.
The device measures hemoglobin and desoxyhemoglobin concentration under the placement area.
This measure is performed, before, during and after the QIF test.
During this test, we measure the hemoglobin and desoxyhemoglobin concentration as well as the tissue saturation index.Quadriceps muscular Oxygen Tissue Saturation will be analysed and compared between excentric and concentric exercise groups from baseline to post-training intervention.
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Day 0, Month 2 (post-training)
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O2 uptake Efficiency during walk test
Time Frame: Day 0, Month 2 (post-training)
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A gaz exchange device records the O2 uptake during the 6 minutes walk test. The O2 uptake efficiency was defined as the volume of O2 per meter used by the participant. An infrared spectroscopy device is localized on the anterior part of the quadriceps. O2 uptake Efficiency during walk test will be analysed and compared between excentric and concentric exercise groups from baseline to post-training intervention. |
Day 0, Month 2 (post-training)
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Creatine Kinase (CPK)
Time Frame: Day 0
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A blood sample collection to measure the CPK concentration.
|
Day 0
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Creatine Kinase (CPK)
Time Frame: Day 7 (post-training)
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A blood sample collection to measure the CPK concentration.
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Day 7 (post-training)
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Creatine Kinase (CPK)
Time Frame: Month 2 (post-training)
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A blood sample collection to measure the CPK concentration.
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Month 2 (post-training)
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C-reactive protein (CRP)
Time Frame: Day 0
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A blood sample collection to measure CRP concentration.
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Day 0
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C-reactive protein (CRP)
Time Frame: Day 7 (post-training)
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A blood sample collection to measure CRP concentration.
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Day 7 (post-training)
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C-reactive protein (CRP)
Time Frame: Month 2 (post-training)
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A blood sample collection to measure CRP concentration.
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Month 2 (post-training)
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Collaborators and Investigators
Investigators
- Principal Investigator: Maxime GROLIER, MD, MSc, CHU de Clermont-Ferrand
- Study Director: Emmanuel COUDEYRE, MD, PhD, CHU de Clermont-Ferrand
Publications and helpful links
General Publications
- Puthucheary ZA, Rawal J, McPhail M, Connolly B, Ratnayake G, Chan P, Hopkinson NS, Phadke R, Dew T, Sidhu PS, Velloso C, Seymour J, Agley CC, Selby A, Limb M, Edwards LM, Smith K, Rowlerson A, Rennie MJ, Moxham J, Harridge SD, Hart N, Montgomery HE. Acute skeletal muscle wasting in critical illness. JAMA. 2013 Oct 16;310(15):1591-600. doi: 10.1001/jama.2013.278481. Erratum In: JAMA. 2014 Feb 12;311(6):625. Padhke, Rahul [corrected to Phadke, Rahul].
- Bailey P, Thomsen GE, Spuhler VJ, Blair R, Jewkes J, Bezdjian L, Veale K, Rodriquez L, Hopkins RO. Early activity is feasible and safe in respiratory failure patients. Crit Care Med. 2007 Jan;35(1):139-45. doi: 10.1097/01.CCM.0000251130.69568.87.
- Needham DM. Mobilizing patients in the intensive care unit: improving neuromuscular weakness and physical function. JAMA. 2008 Oct 8;300(14):1685-90. doi: 10.1001/jama.300.14.1685.
- Wu Y, Xu X, Chen Z, Duan J, Hashimoto K, Yang L, Liu C, Yang C. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020 Jul;87:18-22. doi: 10.1016/j.bbi.2020.03.031. Epub 2020 Mar 30.
- van Zanten ARH, De Waele E, Wischmeyer PE. Nutrition therapy and critical illness: practical guidance for the ICU, post-ICU, and long-term convalescence phases. Crit Care. 2019 Nov 21;23(1):368. doi: 10.1186/s13054-019-2657-5.
- Zhang P, Li J, Liu H, Han N, Ju J, Kou Y, Chen L, Jiang M, Pan F, Zheng Y, Gao Z, Jiang B. Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study. Bone Res. 2020 Feb 14;8:8. doi: 10.1038/s41413-020-0084-5. eCollection 2020. Erratum In: Bone Res. 2020 Sep 21;8:34.
- Connolly B, Salisbury L, O'Neill B, Geneen L, Douiri A, Grocott MP, Hart N, Walsh TS, Blackwood B. Exercise rehabilitation following intensive care unit discharge for recovery from critical illness: executive summary of a Cochrane Collaboration systematic review. J Cachexia Sarcopenia Muscle. 2016 Dec;7(5):520-526. doi: 10.1002/jcsm.12146. Epub 2016 Sep 16.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Respiratory Tract Diseases
- Pneumonia, Viral
- Pneumonia
- Lung Diseases
- Neurologic Manifestations
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Manifestations
- Pathological Conditions, Anatomical
- Muscular Atrophy
- Atrophy
- COVID-19
- Muscle Weakness
- Sarcopenia
- Paresis
Other Study ID Numbers
- PHRCI 2020 COSTE (CovExc)
- 2020-A01201-38 (Other Identifier: ANSM)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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