Cardiopulmonary Rehabilitation in COVID-19 Longhaulers

Not Applicable

• Conditions: Viral Syndrome; Covid19
• Interventions: Other: Treadmill Exercise; Other: Concentrated Oxygen; Other: Concentrated Air

• Registration Number: NCT04898205
• Lead Sponsor: Noah Greenspan

Brief Summary

This study will test the efficacy of treadmill exercise combined with supplemental oxygen during exercise and recovery for the treatment of persistent post-acute COVID-19 symptoms. Participants will be pseudo-randomized (stratified by age) to one of four conditions for 8 treatment sessions: 1) treadmill exercise plus supplemental oxygen, 2) treadmill exercise plus air, 3) supplemental oxygen only, 4) air only. All participants will then cross-over and receive 16 additional sessions of treadmill exercise plus supplemental oxygen.

Detailed Description

This study will test the efficacy of a COVID-19 specific cardiopulmonary rehabilitation protocol for treatment of persistent post-acute COVID symptoms and to study the impact of cardiopulmonary improvement on cognition, mental health, and function. Participants (N=36) with persistent post-acute COVID symptoms will undergo pre-treatment neurocognitive, orthostatic tolerance, and exercise tolerance tests before being pseudo-randomized (stratified by age and sex) to one of four conditions (all of which occur twice a week): 1) 8 sessions of treadmill exercise plus supplemental oxygen, 2) 8 sessions of treadmill exercise plus air, 3) 8 sessions of supplemental oxygen only, and 4) 8 sessions of air only. The pre-treatment testing will be repeated, after which all participants will receive 16 additional sessions of treadmill exercise plus supplemental oxygen, followed by post-treatment testing. All participants will complete baseline measures of physical and mental health, physical function, emotional wellbeing, and coping. A brief symptom measure will be collected daily and physical function, mental health, and emotional wellbeing will be assessed weekly.

Study Timeline

• Study Start: 2021-01-21
• Status Verified: 2021-05
• Study First Submitted: 2021-05-17
• Study First Submitted QC: 2021-05-20
• Last Update Submitted: 2021-05-21
• Study First Posted: 2021-05-24
• Last Update Posted: 2021-05-25
• Primary Completion: 2022-01-20
• Study Completion: 2022-01-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• Between the ages of 18-60
• Contracted COVID-19 between February - July 2020
• Has been clinician-diagnosed with COVID-19 based on PCR/antigen testing, antibody testing, or clinical symptoms
• Is currently experiencing one or more of the following symptoms, which began only after contracting COVID-19 : dyspnea, cough, chest pain, tachycardia or other arrhythmias, hypertension, hypotension, blood pressure lability, oxygen desaturation, exercise/activity intolerance, fatigue, or dizziness.
• Has been cleared by a physician for exercise and supplemental oxygen.
• Has the capacity to provide written, informed consent
• Able to complete questionnaires in English

Exclusion Criteria

• History of any of the following per the American College of Sports Medicine exercise testing guidelines (American College of Sports Medicine et al., 2018) to be determined during a screening consultation:

  1. Acute myocardial infarction within the past two days
  2. Ongoing unstable angina
  3. Uncontrolled cardiac arrhythmias
  4. Active endocarditis
  5. Symptomatic severe aortic stenosis
  6. Decompensated heart failure
  7. Active pulmonary embolism, pulmonary infarction, or deep venous thrombosis
  8. Active myocarditis or pericarditis
  9. Acute aortic dissection
  10. Physical disability that precludes safe and adequate testing

• Participants who demonstrate orthostatic intolerance or oxygen desaturation (<90%) during the exercise tolerance test will no longer be eligible for the study because it is not safe for them to exercise on a treadmill.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treadmill Exercise with Supplemental Oxygen	Treadmill Exercise	Participants will receive 24 sessions (2 x week for 12 weeks) of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
Supplemental Oxygen Only	Treadmill Exercise	Participants will receive 8 treatment sessions (2 x week for 4 weeks) of 6 liters per minute of continuous oxygen via nasal cannula for 30 minutes at rest. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three minutes. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
Supplemental Oxygen Only	Concentrated Oxygen	Participants will receive 8 treatment sessions (2 x week for 4 weeks) of 6 liters per minute of continuous oxygen via nasal cannula for 30 minutes at rest. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three minutes. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
Treadmill Exercise with Air	Treadmill Exercise	Participants will receive 8 sessions (2 x week for 4 weeks) of treadmill exercise combined with air delivered via nasal cannula during exercise and 5-minutes of recovery. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
Treadmill Exercise with Supplemental Oxygen	Concentrated Oxygen	Participants will receive 24 sessions (2 x week for 12 weeks) of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
Treadmill Exercise with Air	Concentrated Air	Participants will receive 8 sessions (2 x week for 4 weeks) of treadmill exercise combined with air delivered via nasal cannula during exercise and 5-minutes of recovery. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
No Intervention	Treadmill Exercise	Participants will receive 8 treatment sessions (2 x week for 4 weeks) of air via nasal cannula for 30 minutes at rest. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three minutes. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
Treadmill Exercise with Air	Concentrated Oxygen	Participants will receive 8 sessions (2 x week for 4 weeks) of treadmill exercise combined with air delivered via nasal cannula during exercise and 5-minutes of recovery. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
No Intervention	Concentrated Air	Participants will receive 8 treatment sessions (2 x week for 4 weeks) of air via nasal cannula for 30 minutes at rest. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three minutes. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.
No Intervention	Concentrated Oxygen	Participants will receive 8 treatment sessions (2 x week for 4 weeks) of air via nasal cannula for 30 minutes at rest. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three minutes. They will then cross-over to 16 sessions of treadmill exercise combined with 6 liters per minute of supplemental oxygen via nasal cannula during exercise and 5-minutes of recovery. The first treadmill session will last 25% longer than the exercise tolerance test, but at a lower intensity, such that 80-100% of peak exercise intensity calculated from the exercise tolerance test MET is achieved within three sessions, after which time and intensity will be increased by no more than 0.5 METS, as tolerated based on symptoms and vitals. Heart rate, rhythm, and oxygen saturation will be continuously monitored, and blood pressure readings will be obtained every three to five minutes.

Primary Outcome Measures

Name	Time	Method
Breathlessness	Up to 24-weeks	Breathlessness will be assessed during peak exercise via self-report using the Borg Dyspnea scale. Scores can range from 0 to 20 and higher scores indicate more breathlessness
Post-acute COVID symptoms (PACS)	Up to 24-weeks	Frequency and severity of 38 PACS symptoms will be assessed daily via an online survey. Each symptom will be rated on a scale of 0 (not present) to 5 (severe).
Heart rate and rhythm response to exercise and positional changes	Up to 24-weeks	Heart rate and rhythm will be measured using 3-lead ECG telemetry
Activity metabolic equivalent of task (MET) tolerated	Up to 24-weeks	MET will be computed based upon peak exercise speed (MPH) and incline % gradation). Scores are expected to range from 1.8 to 12.1 (but can be higher is speed exceeds 3.9 MPH). Higher METs indicate more energy output.
Blood pressure response to exercise and positional changes	Up to 24-weeks	Blood pressure will be measured via manual cuff
Physical Function	Up to 24-weeks	Physical function will be measured weekly via self-report with the Physical Function Short Form-36. Scores can range from 0 to 100 and higher scores indicate better function.
Rate of perceived exertion (RPE)	Up to 24-weeks	RPE will be assessed during peak exercise via self-report using the Borg RPE scale. Scores can range from 0 to 20 and higher scores indicate more RPE.
Cognition (attention, short, delayed, and working memory, verbal fluency, and abstraction).	Up to 24-weeks	Cognition will be assessed with the Repeatable Battery for the Assessment of Neuropsychological Status Update (RBANS-U) List Learning, List Recall, List Recognition, Story Memory, Story Recall, Semantic Fluency and Picture Naming subtests and the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV) Similarities and Digit Span subtests. All scores will be standard scores based on age norms.

Secondary Outcome Measures

Name	Time	Method
Trait anxiety	Up to 24-weeks	Trait anxiety will be measured weekly using the State Trait Anxiety Inventory (STAI) - Trait scale. Scores can range from 20 to 80, with higher scores indicating greater trait anxiety.
Perception of cognitive function	Up to 24-weeks	Perception of cognitive function will be assessed with the Neuro-QOL Cognitive function subscale which measures self-reported cognitive functioning over the past week, including perceptions of memory, executive functions, processing speed, and learning. Raw scores can range from 8 to 40, and will be converted to T-scores based on the administration manual norms. Higher scores indicated better perceived cognitive function.; We have modified the baseline administration to also assess whether perceived cognitive function has changed since onset of acute COVID-19.
Generalized anxiety	Up to 24-weeks	Generalized anxiety will be measured weekly using the Generalized Anxiety Disorder - 2 (GAD-2). Scores range from 0 to 6 and higher scores indicate greater anxiety severity.
Depression	Up to 24-weeks	Depression will be measured weekly with the Center for Epidemiological Studies Depression Scale - Revised (CESD-R). Scores range from 0 to 60 and higher scores indicate greater depression severity.
Improvement in quality of life	Up to 24-weeks	Quality of life will be measured weekly with the Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF). Raw scores range from 14 to 70 and will be converted to a percentage score based on the following formula: (raw total score -minimum score)/(maximum possible raw score -minimum score). Higher scores indicate greater life satisfaction.
State anxiety	Up to 24-weeks	Anxiety will be measured weekly using the State Trait Anxiety Inventory (STAI) - State scale. Scale scores range from 20 to 80, with higher scores indicating greater state anxiety.

Trial Locations

Locations (1)

Post-COVID Rehabilitation and Recovery Clinic at H&D Physical Therapy; 🇺🇸 New York, New York, United States