Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection

COVID-19 Clinical Trial

Official title:

Evaluation of Influence of Proprietary Physical Training Program on Quality of Life, Physical Endurance, Function of Muscles and Myokines Profile in Patients After COVID-19 Infection.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05449379
• Other study ID #: SUB/1/DN/22/001/3309
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2022
• Source: Medical University of Bialystok
• Contact: Mariusz Ciolkiewicz, PhD
• Phone: 858318315
• Email: mariusz.ciolkiewicz[@]umb.edu.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to evaluate the influence of 6 week physical training and respiratory rehabilitation performed in outpatients rehabilitation clinic on quality of life, symptoms, physical endurance, mental state, force of respiratory and skeletal muscles and myokines profile in patients after COVID-19 infection.

Description:

The study of interventional, prospective character will be conducted in Rehabilitation Department of Medical University of Bialystok on total group of 60 participants less than 12 months after COVID-19 (coronavirus disease) infection. In all participants medical anamnesis, physical examination (including chest wall mobility), anthropometric measures, The Short Physical Performance Battery (SPPB), 6-minute walking test (6MWT six minute walking test) and treadmill stress test will be performed.

Medical history will consist of questions regarding course of COVID-19 and its consequences with special emphasis on dyspnea during daily activities in Borg scale and dyspnea in daily living in mMRC scale, coexisting diseases, treatment, lifestyle, etc. Quality of life will be assessed with use of The Short Form (36) Health Survey - SF-36), Post-COVID-19 Functional Status (PCFS] scale and Modified Fatigue Impact Scale (MFIS). Mental status will be evaluated with the use of Beck Depression Inventory (BDI) and Hamilton Depression Scale (HAMD)) Biochemical measures will be performed including, among others, myokines such as BDNF (brain-derived neurotrophic factor), adiponectin, fibroblast growth factor 21 (FGF21), resistin, myonectin and inflammatory markers, such as interleukin 6 ((Il-6), C-reactive protein (CRP).

Fasting venous blood will be collected in 2 tubes each a 10 ml, one dedicated to obtain serum ("on clot"), second with heparin) to perform biochemical analyses, In clinical evaluation measurement of respiratory (inspiratory and expiratory) muscles force with use of device MicroRPM (respiratory pressure meter), hand grip strength with use of hand dynamometer (Jamar) and strength of quadriceps muscles with use of digital dynamometer (AXIS) will be performed. During first visit also ECG (electrocardiogram), six minute walking test and treadmill stress test will be done. All patients will have diaphragm ultrasound with measurement of diaphragm thickness.

Patient will be randomized to the control and interventional groups. Control group will be subjected to the safe protocol of 6 week physical training (aerobic training, resistance training, general improvement training, stretching training and respiratory rehabilitation) adjusted to the clinical state of patients. Additionally patients will be recommended to perform a set of exercises at home under a supervision of physiotherapist.

Patients from interventional group in addition to the training protocol will be subjected to additional resistance respiratory training with the use of respiratory muscle trainer (Philips Respironics Threshold IMT). Control group will have placebo with no resistance set on respiratory muscle trainer (Philips Respironics Threshold IMT). The study will be double blind, patients will be unaware of being assigned to a group and investigators assessing functional state in the next stages of the study will not conduct rehabilitation and will not be aware of the allocation of patients to groups. Physiotherapists conducting rehabilitation will receive detailed, individual guidelines regarding the training parameters of each patient. In addition, both groups will be educated on rules of safe physical activity and how to deal with troublesome symptoms.

Physical endurance (6 MWT, treadmill stress test), respiratory function, respiratory and peripheral muscle strength, other functional tests (SPPB), biochemical determinations, dyspnea (mMRC, Borg scale), quality of life (SF-36, PCFS, MFIS) mental state (BDI, HAMD), chest wall mobility and diaphragm ultrasound will be assessed at the beginning and end of the intervention. In addition, an analysis of the potential change in lifestyle of all patients will be carried out using accelerometry counting daily number of steps and assessing physical activity. Each patient will be equipped with basic exercise equipment and the necessary monitors of physical activity and vital signs to carry out the recommended activities at home (except for training units in the outpatient clinic). A reassessment of the long-term effects will be performed six months after the end of the exercises and will include 6 MWT, treadmill stress test, SPPB, spirometry, measurement of respiratory muscles force, handgrip strength, strength of quadriceps muscles, SF-36, PCFS, MFIS, BDI, HAMD, assessment of dyspnea in Borg scale during daily activities, mMRC, blood samples for biochemical analyses, ), chest wall mobility and diaphragm ultrasound . Patients in both groups will be monitored with the use of accelerometers in order to asses daily activity, daily number of steps within 7 days prior to intervention, after intervention and after observation period.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• COVID 19 infection confirmed with a positive PCR (polymerase chain reaction) SARS-CoV-2 (Severe Scute Respiratory Syndrome coronavirus type 2) test less than 12 moths prior to intervention

• more than 14 days from the day of obtaining a positive PCR test result for SARS-CoV-2 or discharge from hospital.

• mMRC (modified Medical Research Council) score =1

• age >18 years

• informed consent signed by patient to conduct the study

Exclusion Criteria:

• severe pulmonary disease (e.g. COPD)

• the functional state that makes it impossible to carry out the pre-examination and improvement program

• severe chest pain

• worsening dyspnea

• hemoptysis

• worsening dry cough

• syncope

• worsening oedema of extremities

• myocarditis (less than 6 months from acute phase)

Related Conditions & MeSH terms

• COVID-19
• Rehabilitation

Intervention

Other:
• Respiratory training with the use of resistance set on respiratory muscle trainer
Performing respiratory training with resistance set on respiratory trainer.
• Respiratory training without resistance set on respiratory muscle trainer
Performing respiratory training with no resistance set on respiratory trainer

Locations

Country	Name	City	State
Poland	Medical University of Bialystok, Department of Rehabilitation	Bialystok	Podlaskie

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Bialystok

Country where clinical trial is conducted

Poland, 

References & Publications (14)

Ajaz S, McPhail MJ, Singh KK, Mujib S, Trovato FM, Napoli S, Agarwal K. Mitochondrial metabolic manipulation by SARS-CoV-2 in peripheral blood mononuclear cells of patients with COVID-19. Am J Physiol Cell Physiol. 2021 Jan 1;320(1):C57-C65. doi: 10.1152/ajpcell.00426.2020. Epub 2020 Nov 5. — View Citation

Azoulay D, Shehadeh M, Chepa S, Shaoul E, Baroum M, Horowitz NA, Kaykov E. Recovery from SARS-CoV-2 infection is associated with serum BDNF restoration. J Infect. 2020 Sep;81(3):e79-e81. doi: 10.1016/j.jinf.2020.06.038. Epub 2020 Jun 20. — View Citation

Benzarti W, Toulgui E, Prefaut C, Chamari K, Ben Saad H. General practitioners should provide the cardiorespiratory rehabilitation' 'minimum advice' for long COVID-19 patients. Libyan J Med. 2022 Dec;17(1):2009101. doi: 10.1080/19932820.2021.2009101. — View Citation

Cheng YY, Chen CM, Huang WC, Chiang SL, Hsieh PC, Lin KL, Chen YJ, Fu TC, Huang SC, Chen SY, Chen CH, Chen SM, Chen HS, Chou LW, Chou CL, Li MH, Tsai SW, Wang LY, Wang YL, Chou W. Rehabilitation programs for patients with COronaVIrus Disease 2019: consensus statements of Taiwan Academy of Cardiovascular and Pulmonary Rehabilitation. J Formos Med Assoc. 2021 Jan;120(1 Pt 1):83-92. doi: 10.1016/j.jfma.2020.08.015. Epub 2020 Aug 17. Review. — View Citation

Dun Y, Liu C, Ripley-Gonzalez JW, Liu P, Zhou N, Gong X, You B, Du Y, Liu J, Li B, Liu S. Six-month outcomes and effect of pulmonary rehabilitation among patients hospitalized with COVID-19: a retrospective cohort study. Ann Med. 2021 Dec;53(1):2099-2109. doi: 10.1080/07853890.2021.2001043. — View Citation

Fukushima A, Kinugawa S, Homma T, Masaki Y, Furihata T, Yokota T, Matsushima S, Abe T, Suga T, Takada S, Kadoguchi T, Katsuyama R, Oba K, Okita K, Tsutsui H. Decreased serum brain-derived neurotrophic factor levels are correlated with exercise intolerance in patients with heart failure. Int J Cardiol. 2013 Oct 12;168(5):e142-4. doi: 10.1016/j.ijcard.2013.08.073. Epub 2013 Aug 27. — View Citation

Kearns SM, Ahern KW, Patrie JT, Horton WB, Harris TE, Kadl A. Reduced adiponectin levels in patients with COVID-19 acute respiratory failure: A case-control study. Physiol Rep. 2021 Apr;9(7):e14843. doi: 10.14814/phy2.14843. — View Citation

Kirwan R, McCullough D, Butler T, Perez de Heredia F, Davies IG, Stewart C. Sarcopenia during COVID-19 lockdown restrictions: long-term health effects of short-term muscle loss. Geroscience. 2020 Dec;42(6):1547-1578. doi: 10.1007/s11357-020-00272-3. Epub 2020 Oct 1. Review. — View Citation

Liu K, Zhang W, Yang Y, Zhang J, Li Y, Chen Y. Respiratory rehabilitation in elderly patients with COVID-19: A randomized controlled study. Complement Ther Clin Pract. 2020 May;39:101166. doi: 10.1016/j.ctcp.2020.101166. Epub 2020 Apr 1. — View Citation

Nobari H, Fashi M, Eskandari A, Pérez-Gómez J, Suzuki K. Potential Improvement in Rehabilitation Quality of 2019 Novel Coronavirus by Isometric Training System; Is There "Muscle-Lung Cross-Talk"? Int J Environ Res Public Health. 2021 Jun 10;18(12). pii: 6304. doi: 10.3390/ijerph18126304. — View Citation

Sagarra-Romero L, Viñas-Barros A. COVID-19: Short and Long-Term Effects of Hospitalization on Muscular Weakness in the Elderly. Int J Environ Res Public Health. 2020 Nov 24;17(23). pii: E8715. doi: 10.3390/ijerph17238715. Review. — View Citation

Spruit MA, Holland AE, Singh SJ, Tonia T, Wilson KC, Troosters T. COVID-19: Interim Guidance on Rehabilitation in the Hospital and Post-Hospital Phase from a European Respiratory Society and American Thoracic Society-coordinated International Task Force. Eur Respir J. 2020 Aug 13. pii: 2002197. doi: 10.1183/13993003.02197-2020. [Epub ahead of print] — View Citation

Wang TJ, Chau B, Lui M, Lam GT, Lin N, Humbert S. Physical Medicine and Rehabilitation and Pulmonary Rehabilitation for COVID-19. Am J Phys Med Rehabil. 2020 Sep;99(9):769-774. doi: 10.1097/PHM.0000000000001505. Review. — View Citation

Yan H, Ouyang Y, Wang L, Luo X, Zhan Q. Effect of respiratory rehabilitation training on elderly patients with COVID-19: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020 Sep 11;99(37):e22109. doi: 10.1097/MD.0000000000022109. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Physical endurance improvement assessment of 6 MWT distance and outcome of treadmill stress test.	6-min walk test (6 MWT) is a exercise test that entails measurement of distance walked over a span of 6 minutes by patient good outcome > 500 m, bad outcome < 200 m.; Treadmill stress test is performed with use of Bruce or ModBruce (modified Bruce) protocol, the outcome is measured in metabolic equivalents (METs) adjusted to the sex and age	6 months
Primary	Evaluation of quality of life	Quality of life measurement with SF36 (The Short Form (36) Health Survey, which is a 36-item, patient-reported survey of patient health.The Optum™ SF-36v2® Health Survey asks 36 questions to measure functional health and wellbeing from the patient's point of view. It is a practical, reliable and valid measure of physical and mental health that can be completed in five to ten minutes. The more number of points witness of better quality of life. Scores are calibrated so that 50 is the average score or norm. This norm-based score allows comparison among the three surveys and across the more than 19,000 studies published in the past 20 years. This bibliography includes studies of hundreds of diseases, conditions and populations, and greatly enhances the ability to interpret SF health survey data in new studies.Range 0-180 points	6 months
Primary	Force of respiratory muscles	Measurement of maximal inspiratory and expiratory pressure	6 months
Secondary	Spirometry	Measurement of basic parameters as VC (vital capacity), FEV1 (forced expiratory volume in 1 second), FEV1/VC (forced expiratory volume in 1 second//vital capacity) ratio	6 months
Secondary	Force of quadriceps muscles	Measurement the force of quadriceps muscles	6 months
Secondary	Handgrip strength	Measurement of handgrip strength	6 months
Secondary	The Short Physical Performance Battery (SPPB)	Series of tests used to evaluate lower extremity function and mobility including the gait speed, chair stand and balance tests. Range 0-12 points, 0-6 low performance, 10-12 high performance;	6 months
Secondary	Weight	measurement of weight in kilograms	6 months
Secondary	Beck Depression Inventory (BDI)	21-item, self-report rating inventory measuring characteristic attitudes and symptoms of depression. (Range 0-63 ponts, 0-11 points no depression, 50-63 points- severe depression)	6 months
Secondary	Hamilton Depression Scale (HAMD))	Multiple-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery. (Range 0-50 ponts, 0-6points no depression, 25-50 points- severe depression)	6 months
Secondary	Post-COVID-19 Functional Status [PCFS] scale. Range 0-4 0- no limitation of daily functioning, 4 severe limitation of daily functioning	Simple and rapid self-report scale allowing monitoring of the functional impact of the disease	6 months
Secondary	Modified Fatigue Impact Scale (MFIS).	21-item scale measuring the impact of fatigue on a patient's daily life.Range 0-84 points. 0- no impact, 84 very severe impact	6 months
Secondary	Modified Medical Research Council (mMRC)	Modified Medical Research Council (mMRC) most commonly used validated scale to assess dyspnea in daily living in chronic pulmonary diseases. Range 0-4, 0 grade dyspnea only with strenuous exercise, 4 patient too dyspneic to leave house or breathless when dressing	6 months
Secondary	Chest wall mobility	Measurement of chest wall mobility at the level of the xiphoid process and the tenth rib	6 months
Secondary	Diaphragm ultrasound	Measurement of diaphragm thickness in ultrasonography	6 months
Secondary	Modified Borg scale	10 item scale describing dyspnea during daily activities (0- no dyspnea, 10 ver very severe dyspnea)	6 months
Secondary	Concentration of CRP	Measurement of serum concentrations of CRP (C-reactive protein) mg/dl	6 months
Secondary	Concentration of Il-6	Measurement of serum concentrations of interleukin 6 (IL-6) pg/ml	6 months
Secondary	Concentration of BDNF( brain-derived neurotrophic factor)	Measurement of serum concentrations of BDNF ng/ml	6 months
Secondary	Concentration of adiponectin	Measurement of serum concentrations adiponectin ug/ml	6 months
Secondary	Concentration of fibroblast growth factor 21 (FGF21)	Measurement of serum concentrations of fibroblast growth factor 21 (FGF21) ng/ml	6 months
Secondary	Concentration of resistin	Measurement of serum concentrations resistin ng/ml	6 months
Secondary	Concentration of myonectin	Measurement of serum concentrations myonectin ng/ml	6 months