Mechanisms Underlying Long-term Fatigue and Exercise Intolerance Following COVID-19

COVID-19 Clinical Trial

— MEXICO  

Official title:

Mechanisms Underlying Long-term Fatigue and Exercise Intolerance Following SARS-CoV-2 Infection (COVID-19)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04914754
• Other study ID #: 137711
• Status: Completed
• Start date: May 7, 2021
• Est. completion date: January 17, 2023

Study information

• Verified date: May 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The MEXICO study is an observational study that aims to identify underlying mechanisms contributing to exercise intolerance in the presence of persistent COVID-19 symptoms (Long COVID).

Description:

Persistent symptoms of fatigue and severe exercise intolerance have been observed in some patients following infection with CoV-2. Termed 'Long COVID', these symptoms may persist for months after the acute infection has resolved. The mechanisms underlying exercise intolerance in Long COVID are not fully understood and could be the result of dysfunction at any point along the transfer pathway of oxygen from atmosphere to skeletal muscle (uptake in the lungs, heart and blood vessel function and metabolism within skeletal muscle). The primary objective of the MEXICO study was to identify underlying mechanisms that contributed to exercise intolerance in the presence of persistent covid-19 symptoms (long COVID). Initially it was planned that this would involve a comparison of people with long COVID with and without exercise intolerance. It became clear that recruitment to these two groups was unlikely to complete as while most people with long COVID had some degree of exercise intolerance, severe exercise intolerance was infrequent. Consequently the study was revised to include a reference group of healthy individuals with the primary analysis focusing on a comparison of people with and without long COVID. A comparison of people with long COVID with or without severe exercise intolerance was retained as a secondary exploratory analysis. Ethical approval for the measurements conducted in healthy control subjects was granted by the UCL research ethics Committee. Revised sample size calculations for study were based on a two-sample t-test (equal variance for simplicity - although the planned analysis would be using a doubly robust potential outcomes method accounting for potential confounders). Sample size estimates were performed using GPower 3.1.9.7 (alpha = 0.05 (two-tailed) and 80% power) assuming that the minimum clinically important difference for the primary outcomes corresponded to a standardized effect size of 0.88 based on previous studies (typically this represents a 10-20% difference in outcome measure). The study was designed to recruit cases and controls in an approximate proportion of 2:1 to enhance the power of the planned substudy analysis. On this basis 32 and 16 participants were required in the long COVID case and healthy group respectively (48 in total).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: January 17, 2023
• Est. primary completion date: June 20, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Serological or clinical diagnosis of CoV-2 infection
• Ability to provide written informed consent.

Exclusion Criteria:

• < 18 years old.
• Considered a vulnerable adult
• Participant unwilling to consent
• Terminal illness or severe comorbidities affecting attendance or study investigations
• Pregnancy
• If the participant is not willing to give their consent for a clinical advisor to contact them if necessary
• Inability or presence of a contra-indication for exercise testing
• Chronic oral corticosteroid use (e.g. any maintenance dose of oral steroid, 4 or more course of oral steroid in previous 12 months, but not including prescription of dexamethasone during the acute episode of COVID-19, as long as that has been discontinued).

Related Conditions & MeSH terms

• COVID-19

Locations

Country	Name	City	State
United Kingdom	University College London	London

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

References & Publications (3)

Casaburi R. Factors determining constant work rate exercise tolerance in COPD and their role in dictating the minimal clinically important difference in response to interventions. COPD. 2005 Mar;2(1):131-6. doi: 10.1081/copd-200050576. — View Citation

Jones PW, Beeh KM, Chapman KR, Decramer M, Mahler DA, Wedzicha JA. Minimal clinically important differences in pharmacological trials. Am J Respir Crit Care Med. 2014 Feb 1;189(3):250-5. doi: 10.1164/rccm.201310-1863PP. — View Citation

Jones S, Tillin T, Williams S, Eastwood SV, Hughes AD, Chaturvedi N. Type 2 diabetes does not account for ethnic differences in exercise capacity or skeletal muscle function in older adults. Diabetologia. 2020 Mar;63(3):624-635. doi: 10.1007/s00125-019-05055-w. Epub 2019 Dec 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary function (spirometry)	Pulmonary function (ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) (FEV1/FVC)), measured using spirometry, is a co-primary outcome. Compare pulmonary function between long COVID patients with and without severe exercise impairment.	Baseline
Primary	Cardiac function (echocardiography)	Cardiac function (ejection fraction), measured by echocardiography, is a co-primary outcome. Characterise and compare cardiac function between long COVID patients with and without severe exercise impairment.	Baseline
Primary	Microvascular function (microvascular reactivity)	Microvascular reactivity, measured by near-infrared Spectroscopy (NIRS), is a co-primary outcome. Characterise and compare microvascular function between long COVID patients with and without severe exercise impairment.	Baseline
Primary	Macrovascular function (central BP)	Central blood pressure, measured by pulse wave analysis, is a co-primary outcome. Characterise and compare macrovascular function between long COVID patients with and without severe exercise impairment.	Baseline
Primary	Skeletal muscle oxidative capacity	Skeletal muscle oxidative capacity (assessed as the rate of oxygen consumption recovery post-exercise), measured using NIRS, is a co-primary outcome. Characterise and compare skeletal muscle oxidative capacity between long COVID patients with and without severe exercise impairment.	Baseline
Secondary	Change in cardiorespiratory fitness (VO2max)	Compare changes in VO2max, measured on cardiopulmonary exercise testing, to changes in key markers of the oxygen transport pathway (the primary outcomes).	Baseline and 9 months