Rehabilitation and Pacing for Long COVID

No longer recruiting at 45 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify the best methods to help people with Long COVID improve their exercise capacity and manage daily activities. It tests two main treatments: personalized cardiopulmonary rehabilitation (a tailored exercise program) and structured pacing (a method to manage activity levels). These treatments focus on reducing symptoms such as extreme tiredness and shortness of breath following even light activity. Individuals who have had COVID-19 and continue to experience fatigue, shortness of breath, or significant tiredness after simple tasks for at least 12 weeks may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to enhance understanding of effective treatments for Long COVID symptoms.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that personalized heart and lung rehabilitation is generally well-received by patients recovering from severe COVID-19, significantly improving heart and lung function. This treatment includes customized exercise plans with safe levels of strength and endurance exercises.

Structured pacing helps manage energy levels and reduce tiredness after activity, known as post-exertional malaise (PEM). While specific safety data for structured pacing in long COVID patients remains limited, this gentle approach aims to manage symptoms by gradually increasing activity levels.

Both treatments aim to improve exercise capacity and enhance quality of life. Since these treatments do not involve drugs, they usually present fewer risks compared to medication. However, specific safety information for these treatments will become clearer as more studies are completed. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for Long COVID because they offer personalized, non-pharmacological approaches that specifically target different aspects of the condition. The Structured Pacing protocol is designed to help manage post-exertional malaise (PEM) by teaching patients how to balance their activity levels, which is a fresh approach compared to traditional medication or general advice. On the other hand, the Personalized Cardiopulmonary Rehabilitation focuses on improving exercise tolerance through tailored physical therapy, a more individualized approach than standard exercise programs. These treatments aim to provide targeted relief for Long COVID symptoms, potentially leading to more effective management strategies.

What evidence suggests that this trial's treatments could be effective for PASC?

This trial will compare two approaches for managing long-term COVID-19 symptoms. Research has shown that personalized cardiopulmonary rehabilitation, which participants in this trial may receive, can significantly improve the health of people recovering from severe COVID-19 by increasing exercise ability, reducing tiredness, and enhancing quality of life. Another treatment option in this trial is a structured pacing plan, which has proven effective in reducing the frequency and severity of post-exertional malaise (PEM), a condition where individuals feel very tired after activity. These findings suggest that both approaches may help those with long-term COVID-19 symptoms manage their symptoms better and improve their daily lives. ^{2 6 7 8 9}

Who Is on the Research Team?

Janna Friedly, MD, MPH

Principal Investigator

University of Washington

Lucinda Bateman, MD

Principal Investigator

Bateman Horne Center

Gary M Felker, MD

Principal Investigator

Duke Clinical Research Institute

Barry Make, MD

Principal Investigator

National Jewish Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11722468/

A Personalised Pacing and Active Rest Rehabilitation ... Conclusions: A structured pacing protocol effectively reduced PESE episode frequency, duration, and severity but did not produce clinically significant changes ...

2. link.springer.com link.springer.com/article/10.1007/s11357-024-01179-z

Optimizing cardiopulmonary rehabilitation duration for long ... Our follow-up study proved that a 2-week long, patient-centered pulmonary rehabilitation program has a positive long-term effect on people with symptomatic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06404047

NCT06404047 | RECOVER-ENERGIZE Platform Protocol Appendix A is a randomized controlled trial designed to evaluate the effect of a 12-week personalized cardiopulmonary rehabilitation intervention on exercise ...

4. withpower.com withpower.com/trial/phase-post-acute-covid-19-syndrome-5-2024-a611d

Cardiopulmonary Rehabilitation for Long COVID Research shows that personalized cardiopulmonary rehabilitation can significantly improve heart and lung function in patients recovering from severe COVID-19.

5. apm.amegroups.org apm.amegroups.org/article/view/111995/html

Cardiopulmonary rehabilitation programme improves physical ... Outpatient Pulmonary Rehabilitation in Patients with Long COVID Improves Exercise Capacity, Functional Status, Dyspnea, Fatigue, and Quality of Life ...

6. trials.recovercovid.org trials.recovercovid.org/ENERGIZE

recover-energize Without the control groups to use as points of comparison, researchers would not be able to learn how the active study programs affect Long COVID symptoms.

7. withpower.com withpower.com/trial/rehabilitation-and-pacing-for-long-covid-355ce

Rehabilitation and Pacing for Long COVID Research shows that personalized cardiopulmonary rehabilitation can significantly improve heart and lung function in patients recovering from severe COVID-19, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11330745/

Personalized Exercise Prescription in Long COVID Personalized exercise prescription includes resistance training at a submaximal threshold (4–6 exercises, 3 days/week); whole-body endurance exercise titrated ...

9. mdpi.com mdpi.com/2077-0383/14/1/97

A Personalised Pacing and Active Rest Rehabilitation ... A National Evaluation of Outcomes in Long COVID Services Using Digital PROM Data from the ELAROS Platform. LOCO-MOTION and ELAROS, Published by NHS England ...