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Muscular Rehabilitation by Eccentric Exercise After Severe COVID-19 Infection (CovExc)

Primary Purpose

Covid19, Sarcopenia, Muscle Weakness

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Rehabilitation by Eccentric exercises
Rehabilitation by Concentric exercises
Sponsored by
University Hospital, Clermont-Ferrand
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Covid19 focused on measuring Covid19, Sarcopenia, Muscle Weakness, Eccentric exercises, Rehabilitation

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU de Clermont-FerrandRecruiting
  • CHU de DijonRecruiting
  • CHU de Saint-EtienneRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Eccentric group

Concentric group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Functional walking capacity
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.

Secondary Outcome Measures

Evaluating of lower extremity functioning by Short Physical Performance Battery (SPPB) score
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.
Evaluating the maximum muscle strength of the quadriceps by Quadriceps Isometric Maximum Strength (QIMS) test
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.
Evaluating the fatigability of the quadriceps by Quadriceps Intermittent Fatigue (QIF) test
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.
Evaluating the global fatigability by Modified Fatigue Impact Scale (MFIS)
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.
Evaluating functional capacities with EuroQol - 5 Dimensions (EQ-5D) questionnaire
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).
Evaluating the handgrip strength by standard handgrip strength test
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.
Metabolomic Profile
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.
Cross sectional area measurement
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.
Capillary to fibre ratio.
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.
Satellite cell number
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.
Neuromuscular activation
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.
Quadriceps muscular Oxygen Tissue Saturation
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.
O2 uptake Efficiency during walk test
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.
Creatine Kinase (CPK)
A blood sample collection to measure the CPK concentration.
Creatine Kinase (CPK)
A blood sample collection to measure the CPK concentration.
Creatine Kinase (CPK)
A blood sample collection to measure the CPK concentration.
C-reactive protein (CRP)
A blood sample collection to measure CRP concentration.
C-reactive protein (CRP)
A blood sample collection to measure CRP concentration.
C-reactive protein (CRP)
A blood sample collection to measure CRP concentration.

Full Information

First Posted
September 29, 2020
Last Updated
May 18, 2021
Sponsor
University Hospital, Clermont-Ferrand
Collaborators
GIRCI Auvergne Rhône-Alpes, Ministry of Health, France
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1. Study Identification

Unique Protocol Identification Number
NCT04649086
Brief Title
Muscular Rehabilitation by Eccentric Exercise After Severe COVID-19 Infection
Acronym
CovExc
Official Title
Muscular Rehabilitation by Eccentric Exercise After Severe COVID-19 Infection: Research Protocol for Randomized Controlled Trial (CovExc)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Unknown status
Study Start Date
June 5, 2020 (Actual)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
October 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Clermont-Ferrand
Collaborators
GIRCI Auvergne Rhône-Alpes, Ministry of Health, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
This is a prospective, open, controlled randomized study (2 x 60 individuals) performed in 5 centers. Participants will perform 24 exercise sessions on cycloergometer (3 sessions/week, 8 weeks). 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. 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 primary outcome will be the change in distance covered during the 6-min walk test between the initial assessment and month 2. Secondary outcomes will include study of sarcopenia, muscle strength, general and muscular fatigue, quality of life, blood metabolomic data, ex vitro data for mitochondrial and histo-biochemical functionality from muscle biopsies of the Vastus Lateralis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, Sarcopenia, Muscle Weakness
Keywords
Covid19, Sarcopenia, Muscle Weakness, Eccentric exercises, Rehabilitation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
All included participants will be randomly assigned (1:1) using the REDCap software, , at the experimental group or the control group. Participants will perform 24 exercise sessions on cycloergometer (3 sessions/week, 8 weeks). 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. The control group (concentric) will perform exercise training at an intensity of 60% of the reserve heart rate determined during an initial cardiorespiratory test.
Masking
None (Open Label)
Masking Description
Evaluations will be carried out with blinding by investigators different from those involved in the exercise training sessions. Patients will be blinded to the training mode hypothesis.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Eccentric group
Arm Type
Experimental
Arm Description
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.
Arm Title
Concentric group
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Rehabilitation by Eccentric exercises
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Rehabilitation by Concentric exercises
Intervention Description
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.
Primary Outcome Measure Information:
Title
Functional walking capacity
Description
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.
Time Frame
Day 0, Month 1, Month 2 and Month 6
Secondary Outcome Measure Information:
Title
Evaluating of lower extremity functioning by Short Physical Performance Battery (SPPB) score
Description
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.
Time Frame
Day 0, Month 2 and Month 6
Title
Evaluating the maximum muscle strength of the quadriceps by Quadriceps Isometric Maximum Strength (QIMS) test
Description
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.
Time Frame
Day 0, Month 2
Title
Evaluating the fatigability of the quadriceps by Quadriceps Intermittent Fatigue (QIF) test
Description
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.
Time Frame
Day 0, Month 2
Title
Evaluating the global fatigability by Modified Fatigue Impact Scale (MFIS)
Description
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.
Time Frame
Day 0, Month 2 and Month 6
Title
Evaluating functional capacities with EuroQol - 5 Dimensions (EQ-5D) questionnaire
Description
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).
Time Frame
Day 0, Month 2 and Month 6
Title
Evaluating the handgrip strength by standard handgrip strength test
Description
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.
Time Frame
Day 0, Month 2
Title
Metabolomic Profile
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
Cross sectional area measurement
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
Capillary to fibre ratio.
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
Satellite cell number
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
Neuromuscular activation
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
Quadriceps muscular Oxygen Tissue Saturation
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
O2 uptake Efficiency during walk test
Description
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.
Time Frame
Day 0, Month 2 (post-training)
Title
Creatine Kinase (CPK)
Description
A blood sample collection to measure the CPK concentration.
Time Frame
Day 0
Title
Creatine Kinase (CPK)
Description
A blood sample collection to measure the CPK concentration.
Time Frame
Day 7 (post-training)
Title
Creatine Kinase (CPK)
Description
A blood sample collection to measure the CPK concentration.
Time Frame
Month 2 (post-training)
Title
C-reactive protein (CRP)
Description
A blood sample collection to measure CRP concentration.
Time Frame
Day 0
Title
C-reactive protein (CRP)
Description
A blood sample collection to measure CRP concentration.
Time Frame
Day 7 (post-training)
Title
C-reactive protein (CRP)
Description
A blood sample collection to measure CRP concentration.
Time Frame
Month 2 (post-training)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lise Laclautre, PharmD
Phone
04 73 754 963
Ext
33
Email
promo_interne_drci@chu-clermontferrand.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maxime GROLIER, MD, MSc
Organizational Affiliation
CHU de Clermont-Ferrand
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Emmanuel COUDEYRE, MD, PhD
Organizational Affiliation
CHU de Clermont-Ferrand
Official's Role
Study Director
Facility Information:
Facility Name
CHU de Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lise Laclautre, PharmD
Email
promo_interne_drci@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Maxime GROLIER, MD, MSc
Facility Name
CHU de Dijon
City
Dijon
ZIP/Postal Code
21000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lise Laclautre, PharmD
Email
promo_interne_drci@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Paul ORNETTI, MD, PhD
Facility Name
CHU de Saint-Etienne
City
Saint-Étienne
ZIP/Postal Code
42000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lise Laclautre, PharmD
Email
promo_interne_drci@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Léonard FEASSON, MD, PhD

12. IPD Sharing Statement

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Muscular Rehabilitation by Eccentric Exercise After Severe COVID-19 Infection

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