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

Covid19 Clinical Trial

— EXER-COVID  

Official title:

Resistance Training Intervention on the Clinical Status in Patients With Post Discharge Symptoms After Covid-19: The "EXER-COVID Study"

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04797871
• Other study ID #: PI_2020/140
• Status: Completed
• Phase: N/A
• Start date: March 8, 2021
• Est. completion date: September 18, 2022

Study information

• Verified date: July 2022
• Source: Universidad Pública de Navarra
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: September 18, 2022
• Est. primary completion date: September 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Pain
• COVID-19
• Covid19
• Fatigue Syndrome, Chronic
• Pain, Chronic
• SARS-CoV2
• Stress, Psychological

Intervention

Behavioral:
• Resistance training
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.
• Standard care
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.

Locations

Country	Name	City	State
Spain	Robinson Ramírez-Vélez, Ph.D	Pamplona

Sponsors (3)

Lead Sponsor	Collaborator
Universidad Pública de Navarra	Complejo Hospitalario de Navarra, Fundacion Miguel Servet

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Cardiorespiratory fitness	Measured with an incremental VO2 protocol on exercise bike by COSMED Quark CPET plus OMNIA (COSMED®, Rome, Italy)	Baseline, 6 Weeks and 12 Weeks
Secondary	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)	Baseline, 6 Weeks and 12 Weeks
Secondary	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).	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in pulse wave velocity	Measuring pulse wave velocity (m/seg) by VaSera VS 2000 (Fukuda Denshi, Japan)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in cardio-ankle vascular index (CAVI)	Measuring Cardio-Ankle Vascular Index (%) by VaSera VS 2000 (Fukuda Denshi, Japan)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in Energy expenditure	Measuring by COSMED Q-NRG+ plus OMNIA (COSMED®, Rome, Italy)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in bone mineral density measured with DXA	Measuring in bone mineral density (g)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in fat mass measured with DXA	Measuring in fat mass (%)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in lean mass measured with DXA	Measuring in lean mass (kg)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in Fat max oxidation rate	Measured with an incremental VO2 protocol on exercise bike by COSMED k-5 plus OMNIA (COSMED®, Rome, Italy)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in Dynamic and isometric strength	Muscular fitness testing (legs, chest, arms, hip and grip)	Baseline, 6 Weeks and 12 Weeks
Secondary	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)	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in blood samples analysed for markers related to oxidative stress	Including catalase, glutathione peroxidase, peroxidase, glutathione reductase in arbitrary units.	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in creatinine kinase	Creatinine kinase levels (units per liter)	Baseline
Secondary	Changes in total troponins levels (ng/mL)	Total troponins levels (ng/mL)	Baseline
Secondary	Changes in D-dimer	D-dimer (ng/mL)	Baseline
Secondary	Changes in thyroid function parameters	T3 and T4 levels (µg/dL)	Baseline
Secondary	Changes in liver function	ALT in (U/L), AST and GGT in (U/L)	Baseline
Secondary	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)	Baseline
Secondary	Changes in haematology parameters	White Blood Cells and Red Blood Cells (cell characterization)	Baseline
Secondary	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	Baseline, 6 Weeks and 12 Weeks
Secondary	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	Baseline, 6 Weeks and 12 Weeks
Secondary	Changes in Quality of life	Two summary scores are reported from the EuroQOL EQ-5D instrument	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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	Baseline, 6 Weeks and 12 Weeks
Secondary	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.	Baseline, 6 Weeks and 12 Weeks
Secondary	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).	Baseline, 6 Weeks and 12 Weeks
Secondary	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	Baseline, 6 Weeks and 12 Weeks