Rehabilitation and Pacing for Long COVID

Recruiting at 44 trial locations

Overseen By Pinky Agarwal, MD, FAAN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Duke University

Disqualifiers: Active SARS-CoV-2, ME/CFS, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

660 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently using a formal program similar to the study interventions, you may need a washout period (time without taking certain medications) as per the trial's appendices.

What data supports the effectiveness of the treatment Personalized Cardiopulmonary Rehabilitation and Structured Pacing for Long COVID?

Research shows that personalized cardiopulmonary rehabilitation can significantly improve heart and lung function in patients recovering from severe COVID-19, with both low- and high-intensity training proving effective over a 3-month period. This suggests that similar personalized rehabilitation strategies could be beneficial for Long COVID patients. ^{1 2 3 4 5}

Is rehabilitation and pacing for Long COVID safe for humans?

Research on similar rehabilitation programs for heart and lung conditions shows they are generally safe, with minor side effects in some patients. These programs are well-tolerated and do not increase life-threatening events when safety criteria are met. ^{2 3 6 7 8}

How does the treatment 'Personalized Cardiopulmonary Rehabilitation, Structured Pacing' differ from other treatments for Long COVID?

This treatment is unique because it combines personalized cardiopulmonary rehabilitation with structured pacing to manage post-exertional malaise (PEM), a common symptom of Long COVID. It focuses on tailoring exercise protocols to accommodate exercise intolerance and improve overall health, which is different from standard treatments that may not address these specific needs. ^{1 9 10 11 12}

What is the purpose of this trial?

This is a platform protocol designed to be flexible so that it is suitable for a range of interventions and settings within diverse health care systems and community settings with incorporation into clinical COVID-19 management programs and treatment plans if results achieve key study outcomes. This protocol is a prospective, multi-center, multi-arm, randomized, controlled platform trial evaluating interventions to address and improve exercise intolerance and post-exertional malaise (PEM) as manifestations of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). The focus of this protocol is to assess interventions that can improve exercise capacity, daily activities tolerance, and quality of life in patients with PASC.

Research Team

Janna Friedly, MD, MPH

Principal Investigator

University of Washington

Gary M Felker, MD

Principal Investigator

Duke Clinical Research Institute

Barry Make, MD

Principal Investigator

National Jewish Health

Lucinda Bateman, MD

Principal Investigator

Bateman Horne Center

Eligibility Criteria

Adults over 18 who had confirmed or suspected COVID-19 before May 1, 2021, experiencing lasting symptoms like fatigue and shortness of breath for at least 12 weeks. Participants must be able to give consent and complete study tasks. Only a small portion can have unconfirmed cases.

Inclusion Criteria

I have had physical limitations for over 12 weeks due to long COVID.

I am willing to sign consent, answer questions, and follow the study's procedures.

I might have had COVID-19 before May 1, 2021.

Exclusion Criteria

Participation in another interventional clinical trial

Any condition that would make the participant unsuitable for the study

I have been diagnosed with Chronic Fatigue Syndrome not caused by COVID-19.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a 12-week Structured Pacing intervention or a 12-week personalized cardiopulmonary rehabilitation intervention

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

Treatment Details

Interventions

• Personalized Cardiopulmonary Rehabilitation
• Structured Pacing

Trial Overview The trial is testing personalized cardiopulmonary rehabilitation, structured pacing, education against usual care in improving exercise capacity and quality of life in long COVID patients. It's multi-center and randomized.

Participant Groups

Group I: Experimental: Appendix B - Structured Pacing (PEM) Experimental Treatment 2 Interventions

Appendix B is a randomized controlled trial designed to evaluate the effect of a 12-week Structured Pacing intervention on reducing the symptoms of post-exertional malaise (PEM) in participants with PASC. Participants who meet eligibility criteria for Appendix B will be assigned to either Structured Pacing (study intervention group) or Usual Care (control group) in a 1:1 ratio. The intervention duration is 12 weeks with a follow-up period of 3 months (total study duration of 6 months). Anticipated enrollment is 300 participants. Details about Appendix B: Structured Pacing (PEM) are available under NCT06404073.

Group II: Experimental: Appendix A - Cardiopulmonary Rehabilitation (Exercise Intolerance) Experimental Treatment 2 Interventions

Appendix A is a randomized controlled trial designed to evaluate the effect of a 12-week personalized cardiopulmonary rehabilitation intervention on exercise tolerance in participants with PASC. Participants who meet eligibility criteria for Appendix A will be assigned to either Personalized Cardiopulmonary Rehabilitation (study intervention group) or Education (control group) in a 1:1 ratio. The intervention duration is 12 weeks with a follow-up period of 3 months (total study duration of 6 months). Anticipated enrollment is 360 participants. Details about Appendix A: Cardiopulmonary Rehabilitation (Exercise Intolerance) are available under NCT06404060.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Findings from Research

A study of 84 patients recovering from severe COVID-19 showed that both low-intensity and high-intensity rehabilitation significantly improved various cardiopulmonary health markers, including lung function and heart efficiency, over a 3-month period.

Personalized rehabilitation strategies were effective in enhancing recovery, emphasizing the need for tailored approaches based on individual patient needs to optimize long-term cardiopulmonary health post-COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Severe-COVID-19 Cardiopulmonary Rehabilitation: A Comprehensive Study on Patient Features and Recovery Dynamics in Correlation with Workout Intensity. Dumitrescu, A., Doros, G., Lazureanu, VE., et al.[2023]

Exercise training is essential for both preventing and managing cardiovascular disease (CVD), as it can improve quality of life and reduce mortality rates.

Using cardiopulmonary exercise testing helps clinicians create personalized exercise prescriptions based on individual patient characteristics, enhancing the effectiveness of exercise as a treatment for those at risk of or diagnosed with CVD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease. D'Ascenzi, F., Cavigli, L., Pagliaro, A., et al.[2022]

The Cardio-Respiratory Exercise Maugeri Algorithm (CREMA) was found to be a feasible and safe method for tailoring rehabilitation exercise programs for 620 outpatients with various heart and lung diseases over a 4-year period.

Patients who underwent rehabilitation showed significant improvements in physical capabilities, particularly those with recent myocardial revascularization, indicating that personalized exercise training can effectively enhance recovery in patients with chronic heart conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapist Driven Rehabilitation Protocol for Patients with Chronic Heart and Lung Diseases: A Real-Life Study. Simonelli, C., Vitacca, M., Ambrosino, N., et al.[2023]

In a study of 17 patients with chronotropic incompetence, rate response VVIR pacing significantly increased maximal exercise heart rate from 74 to 118 bpm, leading to improved oxygen uptake and exercise tolerance.

The use of VVIR pacing resulted in a 17% increase in exercise tolerance and a 19% increase in exercise time, demonstrating its efficacy in enhancing cardiopulmonary function during exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiopulmonary stress: control of the function of frequency variable pacemaker systems]. Treese, N., Coutinho, M., Ophoff, N., et al.[2013]

Rate adaptive cardiac pacing (RAP) significantly increased peak heart rate (HR) by 15 bpm compared to fixed rate pacing in patients with chronic heart failure, based on a systematic review of 14 studies.

Despite the increase in peak HR, RAP did not lead to a significant improvement in peak exercise capacity (peak VO2), suggesting that while RAP enhances heart rate response, it may primarily benefit cardiac output at lower exercise intensities rather than overall peak performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate adaptive pacing in people with chronic heart failure increases peak heart rate but not peak exercise capacity: a systematic review. Clark, HI., Pearson, MJ., Smart, NA.[2023]

An individualized physical rehabilitation program (PRP) was well tolerated by inotrope-dependent patients with end-stage chronic heart failure (CHF), with over 80% attendance and no life-threatening adverse events reported during the 6-month study involving 120 participants.

The study demonstrated that continued inotropic support (dobutamine or dopamine) does not contraindicate participation in PR, as patients showed comparable exercise intensity and lactate levels to those without inotropic support, indicating safety in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of an Individualized Physical Rehabilitation Program in Patients Dependent on Inotropic Support With End-Stage Chronic Heart Failure. Bortsova, MA., Demchenko, EA., Fedotov, PA., et al.[2023]

Resistive exercise training is considered safe for selected individuals with cardiovascular impairment and can improve muscular strength, endurance, and overall cardiovascular health, making it beneficial for recovery after cardiac events.

Patients should undergo clinical screening and a symptom-limited exercise test before starting resistive training, and those at higher risk for cardiac events should avoid heavy lifting; however, circuit weight training and isometric exercises can enhance strength and self-efficacy with minimal risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistive exercise training in cardiac patients. Recommendations. Verrill, D., Shoup, E., McElveen, G., et al.[2018]

A study involving 24 patients in cardiopulmonary rehabilitation found that exercising while wearing procedural masks still resulted in significant increases in airborne particles, particularly in larger class sizes (four or more participants).

The increase in particle generation peaked around 35 to 40 minutes into the rehabilitation classes, raising concerns about the potential risk of infectious respiratory particles being produced during these sessions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Particulate Generation During Cardiopulmonary Rehabilitation Classes With Patients Wearing Procedural Masks. Helgeson, SA., Taylor, BJ., Lim, KG., et al.[2021]

A study of 176 COVID-19 patients showed that physical performance, measured by the 6-minute walk test, was suboptimal both before discharge and one month later, indicating incomplete recovery after hospitalization.

Younger patients with more extensive lung damage and higher inflammation markers (like ESR) were identified as having a poor recovery trajectory, suggesting that specific predictors can help target rehabilitation efforts more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous physical functional recovery after hospitalization for COVID-19: insights from a 1 month follow-up and a model to predict poor trajectory. Honchar, O., Ashcheulova, T.[2023]

Long COVID affects 25-30% of individuals who have had SARS-CoV-2, leading to symptoms like fatigue and impaired functional capacity, highlighting the need for effective treatment strategies.

Tailored exercise prescriptions can help alleviate symptoms of Long COVID by addressing deconditioning caused by inactivity, suggesting that exercise may be a beneficial management approach for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID. Edward, JA., Peruri, A., Rudofker, E., et al.[2023]

A 6-week structured pacing protocol significantly reduced the average number of post-exertional symptom exacerbation (PESE) episodes in individuals with long-standing post-COVID syndrome, from 3.4 episodes in Week 1 to 1.1 in Week 6.

Participants also experienced improved overall health, as indicated by an increase in EQ-5D 5L scores from 51.4 to 60.6 points, demonstrating both the efficacy of the pacing protocol and its positive impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome. Parker, M., Sawant, HB., Flannery, T., et al.[2023]

Cardio-pulmonary rehabilitation significantly improved physical capacity in 25 discharged COVID-19 patients, with an 18% increase in maximal aerobic capacity (VO2 max) and a 26% increase in maximal workload after 23 rehabilitation sessions.

The program also reduced exercise hyperventilation by 10%, indicating that rehabilitation can enhance respiratory efficiency and overall physical performance in patients recovering from moderate to severe COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of Cardio-Pulmonary Rehabilitation in Moderate to Severe Forms of COVID-19 Infection. Douin, C., Forton, K., Lamotte, M., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Post-Severe-COVID-19 Cardiopulmonary Rehabilitation: A Comprehensive Study on Patient Features and Recovery Dynamics in Correlation with Workout Intensity. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Clinician approach to cardiopulmonary exercise testing for exercise prescription in patients at risk of and with cardiovascular disease. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Therapist Driven Rehabilitation Protocol for Patients with Chronic Heart and Lung Diseases: A Real-Life Study. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

[Cardiopulmonary stress: control of the function of frequency variable pacemaker systems]. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Rate adaptive pacing in people with chronic heart failure increases peak heart rate but not peak exercise capacity: a systematic review. [2023]

6. Russia (Federation) pubmed.ncbi.nlm.nih.gov

Tolerability of an Individualized Physical Rehabilitation Program in Patients Dependent on Inotropic Support With End-Stage Chronic Heart Failure. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Resistive exercise training in cardiac patients. Recommendations. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Characterizing Particulate Generation During Cardiopulmonary Rehabilitation Classes With Patients Wearing Procedural Masks. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Spontaneous physical functional recovery after hospitalization for COVID-19: insights from a 1 month follow-up and a model to predict poor trajectory. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Characteristics and Treatment of Exercise Intolerance in Patients With Long COVID. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Effect of using a structured pacing protocol on post-exertional symptom exacerbation and health status in a longitudinal cohort with the post-COVID-19 syndrome. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Benefits of Cardio-Pulmonary Rehabilitation in Moderate to Severe Forms of COVID-19 Infection. [2022]