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

NCT ID: NCT04914754

Last Updated: 2023-05-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 51 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-05-07
• Study Completion Date: 2023-01-17

Brief 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).

Detailed 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).

Conditions

COVID-19

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Long COVID with mild exercise impairment

Patients with prior serological or clinical diagnosis of CoV-2 infection and a referred to the UCLH Long-COVID clinic for persistent fatigue or exercise intolerance.

No interventions assigned to this group

Healthy Control

Healthy sex-matched and age-matched to within 5 years of Long Covid participants were recruited from UCL staff and students.

No interventions assigned to this group

Long COVID with severe exercise impairment

Patients with prior serological or clinical diagnosis of CoV-2 infection and a referred to the UCLH Long-COVID clinic for persistent fatigue or exercise intolerance and an abnormal walk test criteria included: peripheral oxygen desaturation, \<85% predicted walk distance, a lactate rise\> 1.0 from baseline or a Borg score \> 5 for breathlessness or fatigue at end of test.

No interventions assigned to this group

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University College, London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Professor Hughes

Role: PRINCIPAL_INVESTIGATOR

UCL, University College London

Locations

University College London

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 31820039 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24383418 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17136973 (View on PubMed)

Other Identifiers

137711

Identifier Type: -

Identifier Source: org_study_id