COVID-19 Respiratory InfectionCOVID-RehabNCT05035628
Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue
A study testing Cardiopulmonary exercise training in people with COVID-19 Respiratory Infection, run by Louis Bherer at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- COVID-19 Respiratory Infection
- What is being tested?
- Cardiopulmonary exercise training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteCanada
- Study dates
- 15 Sep 2021to 31 May 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Canada1 site
Preventive medicine and physical activity centre (centre EPIC), Montreal Heart Institute
Montreal, Quebec, H1T1N6
About this study
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.
Read the 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.
- Conditions
- COVID-19 Respiratory Infection
- Being tested
- Cardiopulmonary exercise training
- Keywords
- COVID-19, cardiorespiratory, fitness, cognition, neurovascular coupling, brain functions, physical exercise, rehabilitation, inflammatory markers, long COVID-19, cortical pulsatility
- Medical subject headings
- COVID-19, Motor Activity, Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiopulmonary exercise trainingOther
Participants will follow a 2-month exercise training program, thrice-weekly trainings. The training sessions will start with a 5-min warmup, followed by an aerobic training (20 min) after which 20-min of resistance/muscular training will take place. The program will end with respiratory exercises and cool down period (10 min). Training will be adapted to individuals' baseline capacity as measured by the baseline cardiorespiratory test.
A certified kinesiologist will supervise trainings. Heart rate, oxygen saturation and rating of perceived exertion (Borg Scale, 6-20) will be measured during training sessions.
| Study group | Role | What they receive |
|---|---|---|
| Cardiopulmonary exercise training group | Experimental | Cardiopulmonary exercise intervention will include aerobic exercise, resistance and respiratory exercises, three sessions per week for 2 months Receives: Other: Cardiopulmonary exercise training |
| control group | No intervention | Control group with no intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cardiorespiratory fitness
Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)
Measured: Baseline and post-intervention at 2 months
Secondary outcomes (17)
Change in 6-min walking test performance
maximum distance performed in 6 minutes (distance, m)
Measured: Baseline and post-intervention at 2 months
Change in Functional mobility
Timed up and Go test (s).
Measured: Baseline and post-intervention at 2 months
Change in Lower limb muscles strength
Timed Sit-to-Stand test (s).
Measured: Baseline and post-intervention at 2 months
Change in Quality-of-life
36-Item Short Form Health Survey (Scale ranges from 0-100, with a higher score indicating a better health status).
Measured: Baseline and post-intervention at 2 months
Change in Anxiety
State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).
Measured: Baseline and post-intervention at 2 months
Change in Anxiety
Perceived Stress Scale questionnaire (Score ranges from 0-4, with 0 no stress,1 mild stress, 3 moderate stress and 4 severe).
Measured: Baseline and post-intervention at 2 months
Change in Sleep quality
Pittsburgh Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality). severe).
Measured: Baseline and post-intervention at 2 months
Change in functional respiratory capacity
forced expiratory volume in 1 second (L.)
Measured: Baseline and post-intervention at 2 months
Change in general cognitive functioning
Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning).
Measured: Baseline and post-intervention at 2 months
Change in processing speed
Validated remote version of neuropsychological tests (Z-score)
Measured: Baseline and post-intervention at 2 months
Change in executive functions
Validated remote version of neuropsychological tests (Z-score)
Measured: Baseline and post-intervention at 2 months
Change in episodic memory
Validated remote version of neuropsychological tests (Z-score)
Measured: Baseline and post-intervention at 2 months
Change in inflammatory profile
C-reactive protein (mg/L/L)
Measured: Baseline and post-intervention at 2 months
Change in oxidative stress
serum levels of uric acid (mg/dL), albumin (g/L)
Measured: Baseline and post-intervention at 2 months
Change in markers of coagulation
fibrinogen (g/L)
Measured: Baseline and post-intervention at 2 months
Change in neurovascular coupling
Changes in brain activity evoked by a N-back task and walking relative to baseline will be assessed by t-statistics maps, computed from variations of [HbO] and [HbR] measured by NIRS at the prefrontal cortex.
Measured: Baseline and post-intervention at 2 months
Change in cerebral pulsatility - cortical frontal region
Pulsatility will be measured as the normalized difference of relative near-infrared light intensity changes between systole and diastole, using NIRS in the prefrontal cortical region.
Measured: Baseline and post-intervention at 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start15 Sep 2021
- Primary completion31 May 2023
- Study completion31 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19 Respiratory InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- parallel assignement with 2 groups (1:1)
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Louis Bherer
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Louis Bherer, Montreal Heart Institute
- Investigators
- Louis Bherer, PhD, Principal investigator, Montreal Heart InstituteJacques Malo, MD, Principal investigator, Montreal Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05035628
- Sponsor's protocol ID
- 2021-2956
- Acronym
- COVID-Rehab
- Status last verified
- Nov 2024
- First submitted
- 2 Sep 2021
- Last updated
- 5 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38607276Besnier 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.
PubMed 38917451Besnier 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.
PubMed 35409815
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cardiopulmonary Rehabilitation in Long COVID-19 Patients With Persistent Breathlessness and Fatigue
- ClinicalTrials.gov ID
- NCT05035628
- Acronym / sponsor ID
- COVID-Rehab / 2021-2956
- Conditions
- COVID-19 Respiratory Infection
- Keywords
- COVID-19, cardiorespiratory, fitness, cognition, neurovascular coupling, brain functions, physical exercise, rehabilitation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Louis BhererUniversity, hospital or other
- Study start
- 15 Sep 2021 (actual)
- Primary completion
- 31 May 2023 (actual)
- Study completion
- 31 May 2023 (actual)
- First posted
- 5 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- parallel assignement with 2 groups (1:1)
| Arm | Type | Receives |
|---|---|---|
| Cardiopulmonary exercise training group | Experimental | Other: Cardiopulmonary exercise trainingCardiopulmonary exercise intervention will include aerobic exercise, resistance and respiratory exercises, three sessions per week for 2 months |
| control group | No intervention | –Control group with no intervention. |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cardiopulmonary exercise trainingParticipants will follow a 2-month exercise training program, thrice-weekly trainings. The training sessions will start with a 5-min warmup, followed by an aerobic training (20 min) after which 20-min of resistance/muscular training will take place. The program will end with respiratory exercises and cool down period (10 min). Training will be adapted to individuals' baseline capacity as measured by the baseline cardiorespiratory test. A certified kinesiologist will supervise trainings. Heart rate, oxygen saturation and rating of perceived exertion (Borg Scale, 6-20) will be measured during training sessions. | Other | Cardiopulmonary exercise training group |
Primary outcome
Change in cardiorespiratory fitness
Time frame: Baseline and post-intervention at 2 months
Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)
17 secondary outcomes
Change in 6-min walking test performance
Time frame: Baseline and post-intervention at 2 months
Change in Functional mobility
Time frame: Baseline and post-intervention at 2 months
Change in Lower limb muscles strength
Time frame: Baseline and post-intervention at 2 months
Change in Quality-of-life
Time frame: Baseline and post-intervention at 2 months
Change in Anxiety
Time frame: Baseline and post-intervention at 2 months
Change in Anxiety
Time frame: Baseline and post-intervention at 2 months
Change in Sleep quality
Time frame: Baseline and post-intervention at 2 months
Change in functional respiratory capacity
Time frame: Baseline and post-intervention at 2 months
Change in general cognitive functioning
Time frame: Baseline and post-intervention at 2 months
Change in processing speed
Time frame: Baseline and post-intervention at 2 months
Change in executive functions
Time frame: Baseline and post-intervention at 2 months
Change in episodic memory
Time frame: Baseline and post-intervention at 2 months
Change in inflammatory profile
Time frame: Baseline and post-intervention at 2 months
Change in oxidative stress
Time frame: Baseline and post-intervention at 2 months
Change in markers of coagulation
Time frame: Baseline and post-intervention at 2 months
Change in neurovascular coupling
Time frame: Baseline and post-intervention at 2 months
Change in cerebral pulsatility - cortical frontal region
Time frame: Baseline and post-intervention at 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2024.
- Results publication: PubMed 38607276Gaudreau-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.
- Results publication: PubMed 38917451Besnier 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.
- Derived from this study: PubMed 35409815Besnier 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Louis Bherer, PhD principal investigator
Montreal Heart Institute
Jacques Malo, MD principal investigator
Montreal Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiopulmonary exercise training in people with COVID-19 Respiratory Infection, run by Louis Bherer at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cardiorespiratory fitness (time frame: Baseline and post-intervention at 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05035628, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2024.