Reconditioning Exercise for COVID-19 Patients Experiencing Residual sYmptoms (RECOVERY)

Individuals who had COVID-19 and are thought to have recovered from the disease often experience long-term symptoms such as fatigue, extreme tiredness and shortness of breath, a condition referred to as Long COVID. Previous studies have shown that regular exercise is beneficial for individuals suffering similar symptoms as a result of other diseases such as Chronic Fatigue Syndrome. The goal of this study is determine if participation in a three-month structured exercise program will improve physical function in individuals suffering from Long COVID.

Study Overview

• Status: Withdrawn
• Conditions: Covid19
• Intervention / Treatment: Other: Exercise Therapy

Detailed Description

In December of 2019, a previously unknown betacoronavirus was discovered in the airways of patients with pneumonia in Wuhan, China. The novel coronavirus disease (COVID-19) caused by the virus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) spread rapidly around the world. Common symptoms include cough, fever, dyspnea (i.e. shortness of breath), musculoskeletal aches and pains and fatigue. These symptoms, most notably fatigue and dyspnea, have been reported months after the onset of the disease and often long after patients are thought to have recovered from the disease. Between one and two thirds of patients with milder forms of the disease report symptoms up to two months after the onset of symptoms. This condition is now referred to as Long COVID or Post- Acute Sequelae of SARS-CoV-2 infection, and the characteristic symptoms of this condition are dyspnea and extreme fatigue. Additionally, pulmonary, musculoskeletal, neurological, cardiac, and psychological sequelae in these survivors can affect their physical function and ability to perform activities of daily living. While exercise rehabilitation in patients recovering from COVID-19 has been cautiously recommended, there is little known about the response to exercise in patients with Long COVID-19 nor the optimal methods or strategies for rehabilitating these patients. Understanding the responses to an exercise program is instrumental in designing safe and effective rehabilitation strategies for these patients. The objective of this study is to examine the effect of a 3-month exercise therapy program on physical function in individuals who have recovered from COVID-19 between the previous 2 to 6 months, yet still report symptoms of the disease. The study is a randomized, wait-list-control pilot study designed to gather preliminary data. Participants will be randomized into one of two groups: an immediate treatment group or a wait-list-control group. The immediate treatment group will begin the exercise therapy program following randomization and will participate in the exercise program for a duration of three months. The wait-list-control group will receive usual care for the first three months, after which they will be allowed the opportunity to participate in the exercise therapy program for three months. Outcome measures will me made prior to randomization and following either the three-month exercise program or three months of usual care.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27109
      • Wake Forest University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 55 years of age or older
• Able to read and speak English
• Proof of a positive nucleic acid amplification test for the determination of COVID-19
• Two months post positive nucleic acid amplification test for the determination of COVID
• Self-report of COVID-19 symptoms (symptoms include any of the following: reduced exercise capacity, fatigue, cough, shortness of breath, headache and/or joint pain)
• Able to understand and willing to sign a written informed consent document
• Willing and able to complete all study procedures including attending all exercise sessions

Exclusion Criteria:

• Currently exercising more than 60 minutes per week at a moderate intensity or 30 minutes per week at a high intensity
• Current use of supplemental oxygen
• Active treatment for cancer
• Severe congestive heart failure, pulmonary disease, stroke, peripheral vascular disease, coronary artery disease and/or valvular heart disease
• Positive graded exercise test
• Major psychiatric disease
• Severe liver or hepatic disease
• Uncontrolled hypertension or diabetes
• Orthopedic impairment that prevents participation in an exercise program
• Blindness
• BMI > 40kg/m2
• Living more than 35 miles from exercise facility
• Plans to move within the next 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise Therapy; Exercise therapy will be performed three times per week for 12 weeks.	Other: Exercise Therapy; Each exercise session will involve 5 to10 minutes of stretching and slow walking followed by a 30 minute stimulus phase of aerobic exercise. Exercise intensity during the stimulus phase will be prescribed based on the graded exercise test results and will be gradually increased with the goal of the participant exercising continuously for 30 minutes at 50% to 85% of symptom-limited maximum heart rate, or maintained at a level below that which causes symptomatic or silent ischemia. Following the aerobic phase of exercise, participants will complete one set of 8 to 12 repetitions of muscle-strengthening activities for all major muscle groups (legs, hips, back, abdomen, chest, shoulders, and arms). Participants will be provided with a home based aerobic exercise program. They will be encouraged to perform this home-based program twice a week on days when they are not attending the center-based program.
No Intervention: Wait List Control; Wait-list-control participants will be asked to continue their normal activities over the 12 week period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance Based Physical Function	Six minute walk distance will be used to measure performance based physical function. Subjects will walk at their chosen pace for six minutes on a pre-determined course. Total distance walked will be recorded.	Baseline
Performance Based Physical Function	Six minute walk distance will be used to measure performance based physical function. Subjects will walk at their chosen pace for six minutes on a pre-determined course. Total distance walked will be recorded.	Week 12
Self-reported Physical Function	The Physical Functioning scale of the Medical Outcomes 36 Item Short Form (SF-36) will be used to measure self-reported physical function. Patient responses are rated on a on a 3-point scale (1- yes, limited a lot; 2 - yes, limited a little; or 3- no, not limited at all) and will then be normalized with a mean of 50 and standard deviation of 10.	Baseline
Self-reported Physical Function	The Physical Functioning scale of the Medical Outcomes 36 Item Short Form (SF-36) will be used to measure self-reported physical function. Patient responses are rated on a on a 3-point scale (1- yes, limited a lot; 2 - yes, limited a little; or 3- no, not limited at all) and will then be normalized with a mean of 50 and standard deviation of 10.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical Function	Physical functioning will also be assessed using the Short Physical Performance Battery (SPPB). The SPPB score is based on timed measures of standing balance, walking speed, and ability to rise from a chair. Scores on each measure range from 0 - 4 and will be summed for a final score. Scores for the SPPB range from 0 to 12 with higher scores indicative of greater physical function.	Baseline and Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Volumes and Capacities	Nitrogen (N2) washout will be used to measure the various lung volumes and lung capacities according to American Thoracic Society and European Respiratory Society guidelines.	Baseline and Week 12
Air Flow	Air flow out of the lungs will be measured using spirometry. The forced expiratory volume in one second (FEV1) will be measured according to American Thoracic Society and European Respiratory Society guidelines.	Baseline and Week 12
Diffusion Capacity	Gas exchange will be used to measure the diffusion capacity of the lungs. All measures will be made according to American Thoracic Society and European Respiratory Society guidelines.	Baseline and Week 12
Respiratory Muscle Weakness	Maximum inspiratory strength and maximum expiratory strength will be used to determine respiratory muscle weakness. Maximum inspiratory strength and maximum expiratory strength will be measured as pressures at the mouth generated at residual volume and total lung capacity, respectively. All measures will be made according to American Thoracic Society and European Respiratory Society guidelines.	Baseline and Week 12
Exercise Capacity	Peak oxygen consumption (ml/kg/min) or aerobic capacity will be measured directly during a graded exercise test on an electronically braked cycle ergometer.	Baseline and Week 12
Cognitive Function	The Montreal Cognitive Assessment (MoCA) will be used to characterize global cognitive function. Scores range from 0 to 30, with a score of 26 and higher considered normal.	Baseline and Week 12
Generic Health Related Quality of Life (HRQL) - Physical Component	The SF-36 will be used as a generic measure of HRQL. The SF-36 consists of eight scales. Four of the eight scales will be used to produce a Physical Component score ranging from 0 -100 with lower scores indicative of poorer physical health.	Baseline and Week 12
Generic Health Related Quality of Life (HRQL) - Mental Component	The SF-36 will be used as a generic measure of HRQL. The SF-36 consists of eight scales. Four of the eight scales will be used to produce a Mental Component score ranging from 0 -100 score with lower scores indicative of poorer mental health.	Baseline and Week 12
Disease Specific Health Related Quality of Life (HRQL)	St. George's Respiratory Questionnaire (SGRQ) will be used as a disease specific measure of HRQL. SGRQ consists of three sub-scales. All three scales will be used to produce a score ranging from 0 - 100 score with lower scores indicative of a poorer health related quality of life.	Baseline and Week 12
Disability	The Functional Performance Inventory - Short Form (FPI-SF) will be used to assess disability. The FPI-SF queries participants about performance of activities of daily living to assess disability. Scores range from 0 to 3 with higher scores reflecting better functioning.	Baseline and Week 12
Fatigue	The Chalder Fatigue Score (CFQ-11) will be used to measure the severity of fatigue. Scores range from 0 to 33. Persons without fatigue problems would score 11 or lower.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Investigators: Principal Investigator: Michael J Berry, PhD, Wake Forest University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 12, 2021

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: exercise; rehabilitation; physical function
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: IRB00075690

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All IPD that underlie results in a publication will be made available.
• IPD Sharing Time Frame: Starting 6 months after publication
• IPD Sharing Access Criteria: IPD that underlie results in a publication will be posted to a publicly accessible website following publication.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No