Clinical trial NCT05035628: Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue
Official title: Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: COVID-19 Respiratory Infection
Keywords: COVID-19
cardiorespiratory
fitness
cognition
neurovascular coupling
brain functions
physical exercise
rehabilitation
inflammatory markers
long COVID-19
cortical pulsatility
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
First posted: 2021-09-05
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel assignement with 2 groups (1:1)
Primary purpose: PREVENTION

Brief summary: The objective of this project is to assess the effects of a 2-month cardiopulmonary rehabilitation program on cardiorespiratory fitness in long COVID19 patients. Quality of life, functional capacity, functional respiratory capacity, inflammatory profile, coagulation markers, cognitive functions and brain O2 saturation will also be assessed before and after the exercise rehabilitation program.

Detailed description: Some symptoms such as breathlessness and fatigue appear to persist for several months after COVID-19 infection in about 50% of cases. Stress, anxiety, neurological and cognitive disorders have also been reported in the long-term side effects associated with the disease. Cardiopulmonary rehabilitation programs are recognized as an essential component of the management of people with chronic respiratory disease. These programs are based on exercise training with aerobic exercises, muscle strengthening, breathing exercises. Beyond the benefit on morbi-mortality, a marked improvement in symptoms, fitness and quality of life is observed in chronic respiratory diseases. Several hospital departments, research teams and scientific organizations as the WHO recommend the use of rehabilitation programs for COVID-19 patients.

The main objective is to assess the effects of a 2-month cardiopulmonary rehabilitation program on cardiorespiratory fitness in long COVID19 patients. Secondary objectives include: to characterize baseline and intervention-related changes in quality of life, functional capacity, functional respiratory capacity, inflammatory profile, coagulation markers, cognitive functions, neurovascular coupling and cortical pulsatility.

All participants will have signed a written consent form before taking part in the study.

40 patients who have had COVID-19 with persistent breathlessness and fatigue symptoms after at least 3 months after the diagnosis will be randomly assigned to one of the 2 following study arms : 1/ cardiopulmonary exercise training program; 2/ control group.

Eligibility criteria: Inclusion Criteria:

* Age between 40 and 80
* Individuals infected by the SARS-COV2 virus, with positive PCR diagnosis
* Still having breathlessness and fatigue at least 3 months after the diagnosis of COVID-19 or patients presenting an increase of 1 point (compared to before infection) on the Modified Medical Research Council scale.
* Able to perform a maximal cardiopulmonary stress test and exercise training program in accordance with current guidelines on cardiopulmonary rehabilitation.
* Able to read, understand and sign the information and consent form.

Exclusion Criteria:

* pulmonary embolism diagnosed by scintigraphy
* Absolute and relative contraindication to exercise stress test and / or exercise training
* Recent cardiovascular events (cardiac decompensation or angioplasty or cardiac surgery, less than 1 month; valvular disease requiring surgical correction, active myopericarditis, severe ventricular arrhythmias not stabilized under treatment).
* Kidney failure requiring dialysis
* heart failure (NYHA III or IV)

Primary outcomes:
measure: Change in cardiorespiratory fitness
timeFrame: Baseline and post-intervention at 2 months
Secondary outcomes:
measure: Change in 6-min walking test performance
timeFrame: Baseline and post-intervention at 2 months
measure: Change in Functional mobility
timeFrame: Baseline and post-intervention at 2 months
measure: Change in Lower limb muscles strength
timeFrame: Baseline and post-intervention at 2 months
measure: Change in Quality-of-life
timeFrame: Baseline and post-intervention at 2 months
measure: Change in Anxiety
timeFrame: Baseline and post-intervention at 2 months
measure: Change in Anxiety
timeFrame: Baseline and post-intervention at 2 months
measure: Change in Sleep quality
timeFrame: Baseline and post-intervention at 2 months
measure: Change in functional respiratory capacity
timeFrame: Baseline and post-intervention at 2 months
measure: Change in general cognitive functioning
timeFrame: Baseline and post-intervention at 2 months
measure: Change in processing speed
timeFrame: Baseline and post-intervention at 2 months
measure: Change in executive functions
timeFrame: Baseline and post-intervention at 2 months
measure: Change in episodic memory
timeFrame: Baseline and post-intervention at 2 months
measure: Change in inflammatory profile
timeFrame: Baseline and post-intervention at 2 months
measure: Change in oxidative stress
timeFrame: Baseline and post-intervention at 2 months
measure: Change in markers of coagulation
timeFrame: Baseline and post-intervention at 2 months
measure: Change in neurovascular coupling
timeFrame: Baseline and post-intervention at 2 months
measure: Change in cerebral pulsatility - cortical frontal region
timeFrame: Baseline and post-intervention at 2 months
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Preventive medicine and physical activity centre (centre EPIC), Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Louis Bherer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montreal Heart Institute
name: Jacques Malo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gaudreau-Majeau F, Gagnon C, Djedaa SC, Berube B, Malo J, Iglesies-Grau J, Gayda M, Bherer L, Besnier F. Cardiopulmonary rehabilitation's influence on cognitive functions, psychological state, and sleep quality in long COVID-19 patients: A randomized controlled trial. Neuropsychol Rehabil. 2025 Mar;35(2):345-361. doi: 10.1080/09602011.2024.2338613. Epub 2024 Apr 12.
citation: Besnier F, Malo J, Mohammadi H, Clavet S, Klai C, Martin N, Berube B, Lecchino C, Iglesies-Grau J, Vincent T, Gagnon C, Gaudreau-Majeau F, Juneau M, Simard F, L'Allier P, Nigam A, Gayda M, Bherer L. Effects of Cardiopulmonary Rehabilitation on Cardiorespiratory Fitness and Clinical Symptom Burden in Long COVID: Results From the COVID-Rehab Randomized Controlled Trial. Am J Phys Med Rehabil. 2025 Feb 1;104(2):163-171. doi: 10.1097/PHM.0000000000002559. Epub 2024 Jun 24.
citation: Besnier F, Berube B, Malo J, Gagnon C, Gregoire CA, Juneau M, Simard F, L'Allier P, Nigam A, Iglesies-Grau J, Vincent T, Talamonti D, Dupuy EG, Mohammadi H, Gayda M, Bherer L. Cardiopulmonary Rehabilitation in Long-COVID-19 Patients with Persistent Breathlessness and Fatigue: The COVID-Rehab Study. Int J Environ Res Public Health. 2022 Mar 31;19(7):4133. doi: 10.3390/ijerph19074133.