Clinical trial NCT05449379: Evaluation of Effectiveness of Proprietary Rehabilitation Program in Patients After COVID-19 Infection
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: COVID-19
Rehabilitation
Keywords: COVID-19
rehabilitation
respiratory training
Lead sponsor: Medical University of Bialystok
Sponsor class: OTHER
First posted: 2022-07-08
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Physical endurance improvement assessment of 6 MWT distance and outcome of treadmill stress test.
timeFrame: 6 months
measure: Evaluation of quality of life
timeFrame: 6 months
measure: Force of respiratory muscles
timeFrame: 6 months
Secondary outcomes:
measure: Spirometry
timeFrame: 6 months
measure: Force of quadriceps muscles
timeFrame: 6 months
measure: Handgrip strength
timeFrame: 6 months
measure: The Short Physical Performance Battery (SPPB)
timeFrame: 6 months
measure: Weight
timeFrame: 6 months
measure: Beck Depression Inventory (BDI)
timeFrame: 6 months
measure: Hamilton Depression Scale (HAMD))
timeFrame: 6 months
measure: Post-COVID-19 Functional Status [PCFS] scale. Range 0-4 0- no limitation of daily functioning, 4 severe limitation of daily functioning
timeFrame: 6 months
measure: Modified Fatigue Impact Scale (MFIS).
timeFrame: 6 months
measure: Modified Medical Research Council (mMRC)
timeFrame: 6 months
measure: Chest wall mobility
timeFrame: 6 months
measure: Diaphragm ultrasound
timeFrame: 6 months
measure: Modified Borg scale
timeFrame: 6 months
measure: Concentration of CRP
timeFrame: 6 months
measure: Concentration of Il-6
timeFrame: 6 months
measure: Concentration of BDNF( brain-derived neurotrophic factor)
timeFrame: 6 months
measure: Concentration of adiponectin
timeFrame: 6 months
measure: Concentration of fibroblast growth factor 21 (FGF21)
timeFrame: 6 months
measure: Concentration of resistin
timeFrame: 6 months
measure: Concentration of myonectin
timeFrame: 6 months
Other outcomes:
Locations:
city: Białystok
country: Poland
facility: Medical University of Bialystok, Department of Rehabilitation
state: Podlaskie
Study officials:
affiliation: Medical University of Bialystok
name: Anna Kuryliszyn-Moskal, Professor
role: STUDY_CHAIR
References:
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.
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.
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. No abstract available.
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.
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.
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 Dec 3;56(6):2002197. doi: 10.1183/13993003.02197-2020. Print 2020 Dec.
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.
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. No abstract available.
citation: 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.
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.
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. No abstract available.
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.
citation: Sagarra-Romero L, Vinas-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):8715. doi: 10.3390/ijerph17238715.
citation: Nobari H, Fashi M, Eskandari A, Perez-Gomez 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):6304. doi: 10.3390/ijerph18126304.