RECOVER-ENERGIZE Platform Protocol_Appendix A (Exercise Intolerance)

RECOVER-ENERGIZE: A Platform Protocol for Evaluation of Interventions for Exercise Intolerance in Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Long COVID; Long Covid19; Long Covid-19
• Intervention / Treatment: Behavioral: Personalized Cardiopulmonary Rehabilitation; Other: Education

Detailed Description

Study interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix. Study intervention appendices may be added or removed according to adaptive design and/or emerging evidence.

The platform protocol enrolls participants who meet study eligibility criteria. After completing initial screening assessments, eligible participants are assigned to one of the study intervention appendices that are actively enrolling. Participants must meet certain criteria within a specific appendix in order to be included in that appendix. Once assigned to an appendix, eligible participants are randomized to either the study intervention group or a control group.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • All sites listed under NCT06404047

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• See NCT06404047 for RECOVER-ENERGIZE: Platform Protocol level inclusion and exclusion criteria which applies to this appendix

Additional Appendix A (Cardiopulmonary Rehabilitation (Exercise Intolerance)) Level Exclusion Criteria:

1. Known pre-existing postural orthostatic tachycardia syndrome, not related to SARS-CoV-2 infection
2. Known uncontrolled hypertension (blood pressure [BP] ≥ 160/100 mmHg at rest)
3. Any of the following within 4 weeks of enrollment - acute myocardial infarction, unstable angina, uncontrolled arrhythmias causing symptoms or hemodynamic compromise, acute myocarditis or pericarditis, uncontrolled acutely decompensated heart failure (acute pulmonary edema), acute pulmonary embolism, suspected dissecting aneurysm, severe hypoxemia at rest, thromboembolic event(s), any acute or chronic disorder that may affect exercise capacity or be aggravated by exercise (e.g., infection, exercise induced syncope, thyrotoxicosis, unable to cooperate)
4. Score of 2 or greater for both frequency and severity for any of the first 5 questions on the Screening mDSQ-PEM AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of > 14 hours in item 9 OR Score of 3 or greater on any severity question (regardless of frequency) AND answer of 'YES' to either item 7 or 8 on the Screening mDSQ-PEM, and response of > 14 hours in item 9 OR Any score of 3 or greater on any of the severity questions on the mDSQ-PEM 48-72 hours following the Screening ISWT test
5. A selection of ≥ 8 on question 1 or ≥ 9 on question 3 of the OH Activity Scale from the mOHQ
6. Engaged in purposeful moderate or greater intensity exercise with the intent to improve one's health 2 or more times per week over the 30 days prior to informed consent
7. Inability to walk

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cardiopulmonary Rehabilitation (Exercise Intolerance); Participants assigned to Cardiopulmonary Rehabilitation will undergo a 12-week personalized cardiopulmonary rehabilitation intervention with a follow-up period of 3 months (total study duration of 6 months).	Behavioral: Personalized Cardiopulmonary Rehabilitation; Participants in this group will complete 2-3 cardiopulmonary rehabilitation sessions per week, for 12 weeks, as tolerated. Rehabilitation sessions are provided by respiratory therapists, exercise physiologists, physical therapists, nurses, or others who have experience and training in either pulmonary or cardiac rehabilitation. Rehabilitation sessions (adjusted based on the participant's baseline assessment, symptoms, and progress) last about 1 hour and include education, aerobic exercise, strength, and flexibility training.
Active Comparator: Education; Participants in this group will receive two general education sessions at the start of the intervention with weekly phone/virtual follow-ups from site study staff.	Other: Education; Participants in this group will receive two general education sessions at the start of the intervention with weekly phone/virtual follow-ups from site study staff.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Endurance Shuttle Walk Test (ESWT)	The ESWT consists of timed walking on a 10m course. The result is expressed as total walking time after an initial 2-minute warm-up. The ESWT is an outcome measure of exercise capacity.	Baseline, week 12 (End of Intervention (EOI))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physical function, as measured by the PROMIS SF-Physical Function (PROMIS-PF)	The PROMIS Short Form v2.0 - Physical Function 8b (PROMIS-PF) consists of 8 items. The PROMIS Physical Function instruments measure self-reported capability rather than actual performance of physical activities.	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)
Change in physical function, as measured by actigraphy		Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)
Change in symptom frequency, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)	Symptom frequency is rated on a 5-point Likert scale: 0 = none of the time, 1 = a little of the time, 2 = about half the time, 3 = most of the time, and 4 = all of the time.	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)
Change in symptom severity, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)	Symptom severity is rated on a 5-point Likert scale: 0 = symptom not present, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.	Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)
Change in symptom duration, as measured by the Modified DePaul Symptom Questionnaire - Post-Exertional Malaise (mDSQ-PEM)		Baseline, week 6 (middle of intervention), week 12 (EOI) and week 24 End of Study (EOS)

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Study Chair: Gary M Felker, MD, Duke Clinical Research Institute; Study Chair: Barry Make, MD, National Jewish Health; Study Chair: Lucinda Bateman, MD, Bateman Horne Center; Study Chair: Janna Friedly, MD, MPH, University of Washington

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Actual): March 10, 2026
• Study Completion (Estimated): May 30, 2026

Study Registration Dates

• First Submitted: May 3, 2024
• First Submitted That Met QC Criteria: May 6, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; PASC; PEM (post exertional malaise)
• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Behavior; Post-Acute COVID-19 Syndrome; Motor Activity; Socioeconomic Factors; Population Characteristics; Educational Status
• Other Study ID Numbers: Pro00112409_A; OT2HL156812 (U.S. NIH Grant/Contract); NHLBI Grant to RTI (Other Grant/Funding Number: RTI subcontracting with DCRI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The summary of the results will be shared on the study website: https://recovercovid.org/

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No