Clinical trial NCT05566483: Physiology of Long COVID-19 and the Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity
Official title: Physiological Underpinnings of Post-Acute Sequelae of SARS CoV-2 ("Long COVID") and Impact of Cardiopulmonary Rehabilitation on Quality-of-Life and Functional Capacity
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Post-acute Sequelae of SARS-CoV-2 Infection
Keywords: Cardiopulmonary Rehabilitation
Long COVID
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2022-10-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Randomized control trial
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to establish exercise training as a novel intervention to treat Long COVID and characterize the cardiorespiratory and autonomic physiology in these patients to precisely characterize mechanisms contributing to this syndrome.

Detailed description: Abnormalities observed among Long COVID patients are consistent with cardiac deconditioning. The Long COVID syndrome has been attributed to dysautonomia and/or postural orthostatic tachycardia syndrome (POTS) based largely on anecdotal experience and observations of positional tachycardia among affected individuals. However, it has been emphasized that data are clearly lacking to implicate dysautonomia alone as the cause of Long COVID. Alternatively, cardiac deconditioning leads to a constellation of symptoms, including exercise intolerance, brain fog/cognitive impairments, tachycardia and orthostatic intolerance, all of which are reported among reported among patients with Long COVID. Multiple studies have demonstrated that cardiac deconditioning may occur with as little as 20 hours of bedrest. Exercise training improves cardiorespiratory performance among patients suffering from cardiac deconditioning. Exercise training improves HR regulation and cardiovascular function during submaximal and peak exercise, and improves overall exercise capacity particularly among individuals with cardiac deconditioning following bedrest (e.g. Dallas bedrest studies) and among individuals with postural orthostatic tachycardia syndrome. Our preliminary data demonstrate a significant improvement/resolution in Long-COVID symptoms following a twelve-week exercise training program in a community setting. During the height of the COVID pandemic, the investigators developed an exercise protocol that has been used in the clinical setting to assist with management of patients suffering from Long COVID. This protocol involves recumbent/semi-recumbent exercise - specifically, rowing or cycling on a recumbent ergometer.

This proposal involves a clinical trial involving a two-aim initiative whereby participants with Long COVID will be randomized to a 12-week period of exercise training v. usual care ("controls") with baseline and follow-up assessments in order to: 1) Establish exercise training as a novel treatment strategy for management of Long COVID (Aim 1); and 2) Characterize cardiovascular/autonomic physiology among patients with Long COVID (Aim 2).

There will be a total of 4 visits for testing.

* Baseline Evaluation

  * Visit 1: non-invasive baseline assessment. Visit length \~2 hours.
  * Visit 2: invasive baseline assessment. Visit length \~3 hours.
  * Visit 3: non-invasive, post-exercise assessment. Protocol identical to Visit 1
  * Visit 4: invasive, follow-up assessment. Protocol identical to Visit 2.
* Following completion of Visits 1 and 2, participants will be randomized in a 1:1 ratio to either: 1) Twelve weeks of exercise training (N=15); or 2) Twelve weeks of conservative management (N=15). Thereafter, all participants will complete follow-up evaluation with noninvasive assessment (Visit 3) and invasive assessment (Visit 4), identical to the protocol for Visits 1-2.

Eligibility criteria: Inclusion Criteria:

* Adults ≥18 years with documented history of COVID-19 infection and symptoms consistent with Long COVID lasting \>4 weeks after diagnosis.

Exclusion Criteria:

* History of cardiovascular/pulmonary disease prior to infection
* COVID-related myocardial injury such as evidence of myocarditis
* Deep vein thrombosis/pulmonary embolism following COVID-19 infection
* Exercise intolerance resulting from conditions that are not related to cardiorespiratory or autonomic factors (e.g. osteoarthritis or other musculoskeletal diseases);
* Dependency of supplemental oxygen following COVID infection due to cardiovascular and/or pulmonary complications following acute COVID infection
* body mass index \> 35kg/m2
* age of greater than 65 years.

Primary outcomes:
measure: Characterizing the impact of exercise training (cardiac rehabilitation) on functional capacity among patients with Long COVID
timeFrame: 12 weeks
measure: Characterizing the impact of exercise training (cardiac rehabilitation) on HRqOL among patients with Long COVID
timeFrame: 12 weeks
Secondary outcomes:
measure: Characterization of abnormalities contributing to Long COVID
timeFrame: >12 weeks
measure: Identify the mechanism by which exercise training improves functional capacity and HRqOL among patients with Long COVID
timeFrame: > 12 weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
Study officials:
References:
citation: Larsen NW, Stiles LE, Miglis MG. Preparing for the long-haul: Autonomic complications of COVID-19. Auton Neurosci. 2021 Nov;235:102841. doi: 10.1016/j.autneu.2021.102841. Epub 2021 Jul 3.
citation: Writing Committee; Gluckman TJ, Bhave NM, Allen LA, Chung EH, Spatz ES, Ammirati E, Baggish AL, Bozkurt B, Cornwell WK 3rd, Harmon KG, Kim JH, Lala A, Levine BD, Martinez MW, Onuma O, Phelan D, Puntmann VO, Rajpal S, Taub PR, Verma AK. 2022 ACC Expert Consensus Decision Pathway on Cardiovascular Sequelae of COVID-19 in Adults: Myocarditis and Other Myocardial Involvement, Post-Acute Sequelae of SARS-CoV-2 Infection, and Return to Play: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 May 3;79(17):1717-1756. doi: 10.1016/j.jacc.2022.02.003. Epub 2022 Mar 16. No abstract available.
citation: Mitchell JH, Levine BD, McGuire DK. The Dallas Bed Rest and Training Study: Revisited After 50 Years. Circulation. 2019 Oct 15;140(16):1293-1295. doi: 10.1161/CIRCULATIONAHA.119.041046. Epub 2019 Oct 14. No abstract available.
citation: Saltin B, Blomqvist G, Mitchell JH, Johnson RL Jr, Wildenthal K, Chapman CB. Response to exercise after bed rest and after training. Circulation. 1968 Nov;38(5 Suppl):VII1-78. No abstract available.
citation: Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of Cardiopulmonary Stress Testing for Patients With Unexplained Dyspnea Post-Coronavirus Disease. JACC Heart Fail. 2021 Dec;9(12):927-937. doi: 10.1016/j.jchf.2021.10.002.