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Resistance Training and Clinical Status in Patients With Post Discharge Symptoms After Covid-19 (EXER-COVID)

Primary Purpose

Covid19, SARS-CoV2, Fatigue Syndrome, Chronic

Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Resistance training
Standard care
Sponsored by
Universidad Pública de Navarra
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional health services research trial for Covid19

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years
  • SARS-CoV-2 diagnosed using real-time reverse transcriptase polymerase chain reaction (PCR) tests or positive for SARS-CoV-2 virus antigen >90 days before randomization.
  • Still present a chronic symptomatic phase lasting >90 days since debut of symptoms.
  • Have not been hospitalized.
  • There is no evidence on clinical records of pneumonia or any other organ failure related to SARS-CoV-2.
  • Capable and willing to provide an informed consent.

Exclusion Criteria:

  • Pregnancy or breast-feeding.
  • Present atrial fibrillation.
  • Diagnosed with acute myocarditis.
  • Health conditions that prevent participating in the exercise intervention
  • Patients who cannot undergo VO2max (e.g. acute heart attack or unstable angina, aortic stenosis, acute endocarditis / pericarditis, uncontrolled high blood pressure, acute thromboembolism, severe heart failure, respiratory failure and uncontrolled acute decompensated diabetes mellitus or low blood sugar).
  • Treatment with IL-6 receptor antagonists (tocilizumab, kevzara) within the last month due to drug interference with the cardiopulmonary exercise adaptations.

Sites / Locations

  • Robinson Ramírez-Vélez, Ph.D

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Exercise

Standard care

Arm Description

Resistance training

Non-supervised ACSM exercise guidelines

Outcomes

Primary Outcome Measures

Changes in Cardiorespiratory fitness
Measured with an incremental VO2 protocol on exercise bike by COSMED Quark CPET plus OMNIA (COSMED®, Rome, Italy)

Secondary Outcome Measures

Changes in Post-COVID manifestations
Questionnaires that sought information about symptoms related to COVID-19 will be administrate. It is a dichotomous scale (Yes/No), that reflects symptoms, functional limitations, and clinical characteristics (i.e., nausea/vomiting, impaired visual acuity or blurry vision, anosmia, dizziness, depression, chills, weakness, musculoskeletal pain, palpitations/tachycardia, change of appetite, frustration, cognitive involvement, anxiety/irritability, dryness, impaired concentration, and headache)
Changes in Blood samples analysed for markers related to low grade inflammation
Including ENA-78, GCSF, GM-CSF, GRO, GRO-alpha, I-309, IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p40/p70, IL-13, IL-15, IFN-gamma, MCP-1, MCP-2, MCP-3, MCSF, MDC, MIG, MIP-1delta, RANTES, SCF, SDF-1, TARC, TGF-beta1, TNF-alpha, TNF-beta, EGF, IGF-I, Angiogenin, Oncostatin M, Thrombopoietin, VEGF-A, PDGF BB, Leptin in (arbitrary units).
Changes in pulse wave velocity
Measuring pulse wave velocity (m/seg) by VaSera VS 2000 (Fukuda Denshi, Japan)
Changes in cardio-ankle vascular index (CAVI)
Measuring Cardio-Ankle Vascular Index (%) by VaSera VS 2000 (Fukuda Denshi, Japan)
Changes in Energy expenditure
Measuring by COSMED Q-NRG+ plus OMNIA (COSMED®, Rome, Italy)
Changes in bone mineral density measured with DXA
Measuring in bone mineral density (g)
Changes in fat mass measured with DXA
Measuring in fat mass (%)
Changes in lean mass measured with DXA
Measuring in lean mass (kg)
Changes in Fat max oxidation rate
Measured with an incremental VO2 protocol on exercise bike by COSMED k-5 plus OMNIA (COSMED®, Rome, Italy)
Changes in Dynamic and isometric strength
Muscular fitness testing (legs, chest, arms, hip and grip)
Changes in Axial accelerometer-based physical activity monitors
Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK)
Changes in blood samples analysed for markers related to oxidative stress
Including catalase, glutathione peroxidase, peroxidase, glutathione reductase in arbitrary units.
Changes in serum metabolic profiles
Utrahigh-performance liquid chromatography (UHPLC)-time of flight-MS based platforms analyzing methanol and chloroform/methanol serum extracts will be combined with the lipids measurement using an UHPLC-single quadrupole-MS based analysis in arbitrary units. Explained fraction of variance and the goodness of prediction will be calculated.
Changes in creatinine kinase
Creatinine kinase levels (units per liter)
Changes in total troponins levels (ng/mL)
Total troponins levels (ng/mL)
Changes in D-dimer
D-dimer (ng/mL)
Changes in thyroid function parameters
T3 and T4 levels (μg/dL)
Changes in liver function
ALT in (U/L), AST and GGT in (U/L)
Changes in renal function
Urea (mmol/L), sodium (mmol/L), potassium (mmol/L), chloride (mmol/L), calcium (mmol/L), inorganic phosphorus (mmol/L) and uric acid (mmol/L)
Changes in haematology parameters
White Blood Cells and Red Blood Cells (cell characterization)
Changes in cognitive status
Montreal Cognitive Assessment (MOCA) will be used as an indicator of cognitive status. Scores range between 0 and 30. A score of 26 or over is considered to be normal
Changes in visual attention and task switching
The Trail Making Test will be used as an indicator of visual scanning, graphomotor speed, and executive function. This test consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy
Changes in Quality of life
Two summary scores are reported from the EuroQOL EQ-5D instrument
Changes in psychological stress
The 1 Item Statistics Canada Stress Question (SCSQ) will be used. The SCSQ is a 1-item question with a possible scoring of 0 to 10, with higher scores indicating more stress.
Changes in physical health symptomology
A Physical Health item will be used in the baseline. The scoring range is 0-13, with higher numbers indicating experiencing more negative physical health symptoms.
Changes in psychological distress
The 10 Item Kessler Psychological Distress Scale will be used. Scores range from 10-50, with higher scores indicating more symptoms or more frequent experience of those symptoms.
Changes in depressive symptomology
The 10 Item Center for Epidemiologic Studies Depression Scale (CES-D) will be used in the baseline survey, and will be in each weekly survey to track changes in the CES-D over the study period. The possible range in scores is 0 to 30 depending on number of symptoms, with those symptoms weighted by frequency experienced in a week. Higher scores indicating more or more frequent symptoms.
Changes in life satisfaction
A Life Satisfaction item, consisting of three questions, will be used (scored 0-10). Higher scores indicate "the best possible life overall". In addition, 2-follow-up questions asking individuals to rate their physical and mental/emotional health on a five point scale from poor to excellent. Higher scores overall indicate more satisfaction with life.
Changes in resilience
The Brief Resilience Scale will be used (scores from 1-5). Higher scores indicate the individual perceives they have a better ability to 'bounce back' and recover from stressful events and/or situations.
Change in pain score using numeric 0-10 rating scale
The numeric rating scale is 0-10 where 0 is no pain, 5 is moderate pain and 10 is the worst pain
Tracking the amount of exercise variety participants feel they engage in
Using the Perceived Variety in Exercise questionnaire. There are 5 items asking about exercise variety, scored 1 (false) to 6 (true), with a possible score of 5-30; higher scores indicate greater perceived variety.
Changes in physical activity levels
Metabolic Equivalents (METs) throughout a week, including activity for work, during transport and leisure time, using the self-reported general physical activity questionnaire (GPAQ).
Including Changes in mononuclear cells of peripheral blood (sub-sample 40 participants)
CD4, CD8, PD1, CD62L, LKRG1, CD28, CD57, CD163, CD119, CD56, CD116, CD66b, CD11b, and CD14 by flow cytometry

Full Information

First Posted
March 8, 2021
Last Updated
October 31, 2022
Sponsor
Universidad Pública de Navarra
Collaborators
Fundacion Miguel Servet, Complejo Hospitalario de Navarra
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1. Study Identification

Unique Protocol Identification Number
NCT04797871
Brief Title
Resistance Training and Clinical Status in Patients With Post Discharge Symptoms After Covid-19
Acronym
EXER-COVID
Official Title
Resistance Training Intervention on the Clinical Status in Patients With Post Discharge Symptoms After Covid-19: The "EXER-COVID Study"
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
March 8, 2021 (Actual)
Primary Completion Date
September 18, 2022 (Actual)
Study Completion Date
September 18, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universidad Pública de Navarra
Collaborators
Fundacion Miguel Servet, Complejo Hospitalario de Navarra

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
COVID-19 survivors commonly exhibit a marked extra-respiratory complication affecting the cardiac (arrhythmias and myocardial injury), renal (acute kidney injury), gastrointestinal, nervous (neuropathy, encephalopathy), endocrine and musculoskeletal (weakness, pain, and fatigue) systems. In this context, several studies have found that resistance training intervention promotes important health-related benefits, including cardiac function, compared to aerobic exercise training. Other exercise adaptations include increased skeletal muscle metabolism function, yet physio/psychological adaptations are known to be limited in COVID-19 survivors. Hence, given that resistance training intervention is implemented in a manner that is tolerable to the individual patient, it may be a potential beneficiary "personalized" rehabilitation treatment for patients with COVID-19 syndrome ambulatory. The "EXER-COVID Clinical Study" project aims at determining the role of personalized exercise intervention in the treatment of post-COVID-19 syndrome ambulatory patients.
Detailed Description
100 patients will be recruited and undergo baseline testing, including examination, immune systems, biochemistry markers, ECG, DXA, metabolic/respiratory function, VO2max, muscular fitness, lipidomic/inflammatory/oxidative markers and psychological outcomes. After baseline testing, participants will be randomly allocated into one group receiving standard of care (control group) or a group performing personalized resistance training intervention two times a week over a period of 6 weeks. The randomization procedure involves a computer-generated block randomization schedule in a ratio of 1:1 stratified by an independent person. Following the 8-week intervention period (with a 1-week washout period), both groups will complete a series of follow-up tests (as baseline testing). A 12-week follow-up experimental day is also planned in order to evaluate physio/psychological changes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Covid19, SARS-CoV2, Fatigue Syndrome, Chronic, Stress, Psychological, Pain, Chronic

7. Study Design

Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
Investigator
Masking Description
Single (Investigator)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Exercise
Arm Type
Experimental
Arm Description
Resistance training
Arm Title
Standard care
Arm Type
Active Comparator
Arm Description
Non-supervised ACSM exercise guidelines
Intervention Type
Behavioral
Intervention Name(s)
Resistance training
Intervention Description
Participants will complete a 2-days-a-week training routine: Resistance training (RT, 50-75% 1RM (one-repetition maximum), 4 sets, 8-12 repetitions, 4 exercises). The warn up include Light Intensity Continuous Training (8-10 min, 65-70% HRR). Progressions will be individualized and consistent with patient tolerance. Sessions will be supervised by Physiotherapists and Graduated in Sports Sciences.
Intervention Type
Behavioral
Intervention Name(s)
Standard care
Intervention Description
This group will be allocated to standard care and therefore no supervised exercise regimen according to scientific guidelines for general physical activity and return to sport provided by the ACSM guidelines for Chronic Obstructive Pulmonary Disease and Cardiovascular Disease.
Primary Outcome Measure Information:
Title
Changes in Cardiorespiratory fitness
Description
Measured with an incremental VO2 protocol on exercise bike by COSMED Quark CPET plus OMNIA (COSMED®, Rome, Italy)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Secondary Outcome Measure Information:
Title
Changes in Post-COVID manifestations
Description
Questionnaires that sought information about symptoms related to COVID-19 will be administrate. It is a dichotomous scale (Yes/No), that reflects symptoms, functional limitations, and clinical characteristics (i.e., nausea/vomiting, impaired visual acuity or blurry vision, anosmia, dizziness, depression, chills, weakness, musculoskeletal pain, palpitations/tachycardia, change of appetite, frustration, cognitive involvement, anxiety/irritability, dryness, impaired concentration, and headache)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in Blood samples analysed for markers related to low grade inflammation
Description
Including ENA-78, GCSF, GM-CSF, GRO, GRO-alpha, I-309, IL-1alpha, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 p40/p70, IL-13, IL-15, IFN-gamma, MCP-1, MCP-2, MCP-3, MCSF, MDC, MIG, MIP-1delta, RANTES, SCF, SDF-1, TARC, TGF-beta1, TNF-alpha, TNF-beta, EGF, IGF-I, Angiogenin, Oncostatin M, Thrombopoietin, VEGF-A, PDGF BB, Leptin in (arbitrary units).
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in pulse wave velocity
Description
Measuring pulse wave velocity (m/seg) by VaSera VS 2000 (Fukuda Denshi, Japan)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in cardio-ankle vascular index (CAVI)
Description
Measuring Cardio-Ankle Vascular Index (%) by VaSera VS 2000 (Fukuda Denshi, Japan)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in Energy expenditure
Description
Measuring by COSMED Q-NRG+ plus OMNIA (COSMED®, Rome, Italy)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in bone mineral density measured with DXA
Description
Measuring in bone mineral density (g)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in fat mass measured with DXA
Description
Measuring in fat mass (%)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in lean mass measured with DXA
Description
Measuring in lean mass (kg)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in Fat max oxidation rate
Description
Measured with an incremental VO2 protocol on exercise bike by COSMED k-5 plus OMNIA (COSMED®, Rome, Italy)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in Dynamic and isometric strength
Description
Muscular fitness testing (legs, chest, arms, hip and grip)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in Axial accelerometer-based physical activity monitors
Description
Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK)
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in blood samples analysed for markers related to oxidative stress
Description
Including catalase, glutathione peroxidase, peroxidase, glutathione reductase in arbitrary units.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in serum metabolic profiles
Description
Utrahigh-performance liquid chromatography (UHPLC)-time of flight-MS based platforms analyzing methanol and chloroform/methanol serum extracts will be combined with the lipids measurement using an UHPLC-single quadrupole-MS based analysis in arbitrary units. Explained fraction of variance and the goodness of prediction will be calculated.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in creatinine kinase
Description
Creatinine kinase levels (units per liter)
Time Frame
Baseline
Title
Changes in total troponins levels (ng/mL)
Description
Total troponins levels (ng/mL)
Time Frame
Baseline
Title
Changes in D-dimer
Description
D-dimer (ng/mL)
Time Frame
Baseline
Title
Changes in thyroid function parameters
Description
T3 and T4 levels (μg/dL)
Time Frame
Baseline
Title
Changes in liver function
Description
ALT in (U/L), AST and GGT in (U/L)
Time Frame
Baseline
Title
Changes in renal function
Description
Urea (mmol/L), sodium (mmol/L), potassium (mmol/L), chloride (mmol/L), calcium (mmol/L), inorganic phosphorus (mmol/L) and uric acid (mmol/L)
Time Frame
Baseline
Title
Changes in haematology parameters
Description
White Blood Cells and Red Blood Cells (cell characterization)
Time Frame
Baseline
Title
Changes in cognitive status
Description
Montreal Cognitive Assessment (MOCA) will be used as an indicator of cognitive status. Scores range between 0 and 30. A score of 26 or over is considered to be normal
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in visual attention and task switching
Description
The Trail Making Test will be used as an indicator of visual scanning, graphomotor speed, and executive function. This test consists of two parts in which the subject is instructed to connect a set of 25 dots as quickly as possible while still maintaining accuracy
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in Quality of life
Description
Two summary scores are reported from the EuroQOL EQ-5D instrument
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in psychological stress
Description
The 1 Item Statistics Canada Stress Question (SCSQ) will be used. The SCSQ is a 1-item question with a possible scoring of 0 to 10, with higher scores indicating more stress.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in physical health symptomology
Description
A Physical Health item will be used in the baseline. The scoring range is 0-13, with higher numbers indicating experiencing more negative physical health symptoms.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in psychological distress
Description
The 10 Item Kessler Psychological Distress Scale will be used. Scores range from 10-50, with higher scores indicating more symptoms or more frequent experience of those symptoms.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in depressive symptomology
Description
The 10 Item Center for Epidemiologic Studies Depression Scale (CES-D) will be used in the baseline survey, and will be in each weekly survey to track changes in the CES-D over the study period. The possible range in scores is 0 to 30 depending on number of symptoms, with those symptoms weighted by frequency experienced in a week. Higher scores indicating more or more frequent symptoms.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in life satisfaction
Description
A Life Satisfaction item, consisting of three questions, will be used (scored 0-10). Higher scores indicate "the best possible life overall". In addition, 2-follow-up questions asking individuals to rate their physical and mental/emotional health on a five point scale from poor to excellent. Higher scores overall indicate more satisfaction with life.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in resilience
Description
The Brief Resilience Scale will be used (scores from 1-5). Higher scores indicate the individual perceives they have a better ability to 'bounce back' and recover from stressful events and/or situations.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Change in pain score using numeric 0-10 rating scale
Description
The numeric rating scale is 0-10 where 0 is no pain, 5 is moderate pain and 10 is the worst pain
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Tracking the amount of exercise variety participants feel they engage in
Description
Using the Perceived Variety in Exercise questionnaire. There are 5 items asking about exercise variety, scored 1 (false) to 6 (true), with a possible score of 5-30; higher scores indicate greater perceived variety.
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Changes in physical activity levels
Description
Metabolic Equivalents (METs) throughout a week, including activity for work, during transport and leisure time, using the self-reported general physical activity questionnaire (GPAQ).
Time Frame
Baseline, 6 Weeks and 12 Weeks
Title
Including Changes in mononuclear cells of peripheral blood (sub-sample 40 participants)
Description
CD4, CD8, PD1, CD62L, LKRG1, CD28, CD57, CD163, CD119, CD56, CD116, CD66b, CD11b, and CD14 by flow cytometry
Time Frame
Baseline, 6 Weeks and 12 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years SARS-CoV-2 diagnosed using real-time reverse transcriptase polymerase chain reaction (PCR) tests or positive for SARS-CoV-2 virus antigen >90 days before randomization. Still present a chronic symptomatic phase lasting >90 days since debut of symptoms. Have not been hospitalized. There is no evidence on clinical records of pneumonia or any other organ failure related to SARS-CoV-2. Capable and willing to provide an informed consent. Exclusion Criteria: Pregnancy or breast-feeding. Present atrial fibrillation. Diagnosed with acute myocarditis. Health conditions that prevent participating in the exercise intervention Patients who cannot undergo VO2max (e.g. acute heart attack or unstable angina, aortic stenosis, acute endocarditis / pericarditis, uncontrolled high blood pressure, acute thromboembolism, severe heart failure, respiratory failure and uncontrolled acute decompensated diabetes mellitus or low blood sugar). Treatment with IL-6 receptor antagonists (tocilizumab, kevzara) within the last month due to drug interference with the cardiopulmonary exercise adaptations.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikel Izquierdo, Ph.D
Organizational Affiliation
Universidad Publica de Navarra
Official's Role
Study Chair
Facility Information:
Facility Name
Robinson Ramírez-Vélez, Ph.D
City
Pamplona
ZIP/Postal Code
31001
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35945634
Citation
Ramirez-Velez R, Oteiza J, de Tejerina JMCF, Garcia-Alonso N, Legarra-Gorgonon G, Oscoz-Ochandorena S, Arasanz H, Garcia-Alonso Y, Correa-Rodriguez M, Izquierdo M. Resistance training and clinical status in patients with postdischarge symptoms after COVID-19: protocol for a randomized controlled crossover trial "The EXER-COVID Crossover Study". Trials. 2022 Aug 9;23(1):643. doi: 10.1186/s13063-022-06608-y.
Results Reference
derived

Learn more about this trial

Resistance Training and Clinical Status in Patients With Post Discharge Symptoms After Covid-19

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