COVID-19MEXICONCT04914754
Mechanisms Underlying Long-term Fatigue and Exercise Intolerance Following COVID-19
An observational study of COVID-19, run by University College, London at 1 site in United Kingdom.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- How many people
- 51 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 7 May 2021to 17 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Study population (n=51) are either patients with symptoms of Long COVID who have been referred for clinical investigation (with or without severe exercise impairment) or healthy controls.
Who may be able to join
- Serological or clinical diagnosis of CoV-2 infection
- Ability to provide written informed consent.
Who cannot join
- < 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mechanisms Underlying Long-term Fatigue and Exercise Intolerance Following SARS-CoV-2 Infection (COVID-19)
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).
Read the 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
- Keywords
- Long COVID, Exercise intolerance, Quality of Life, Coronavirus
- Medical subject headings
- COVID-19, Post-Acute COVID-19 Syndrome, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| Healthy Control | Healthy sex-matched and age-matched to within 5 years of Long Covid participants were recruited from UCL staff and students. | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline
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.
Measured: Baseline
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.
Measured: Baseline
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.
Measured: Baseline
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.
Measured: Baseline
Secondary outcomes (1)
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).
Measured: Baseline and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2021
- Study start7 May 2021
- Primary completion20 Jun 2022
- Study completion17 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Professor Hughes, Principal investigator, UCL, University College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04914754
- Sponsor's protocol ID
- 137711
- Acronym
- MEXICO
- Status last verified
- May 2023
- First submitted
- 26 Apr 2021
- Last updated
- 16 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 31820039Jones 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.
PubMed 24383418Casaburi 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.
PubMed 17136973Jamieson A, Al Saikhan L, Alghamdi L, Hamill Howes L, Purcell H, Hillman T, Heightman M, Treibel T, Orini M, Bell R, Scully M, Hamer M, Chaturvedi N, Montgomery H, Hughes AD, Astin R, Jones S. Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction. Physiol Rep. 2024 Feb;12(3):e15940. doi: 10.14814/phy2.15940.
PubMed 38346773
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms Underlying Long-term Fatigue and Exercise Intolerance Following SARS-CoV-2 Infection (COVID-19)
- ClinicalTrials.gov ID
- NCT04914754
- Acronym / sponsor ID
- MEXICO / 137711
- Conditions
- COVID-19
- Keywords
- Long COVID, Exercise intolerance, Quality of Life, Coronavirus
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Study start
- 7 May 2021 (actual)
- Primary completion
- 20 Jun 2022 (actual)
- Study completion
- 17 Jan 2023 (actual)
- First posted
- 7 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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. |
| Healthy Control | – | –Healthy sex-matched and age-matched to within 5 years of Long Covid participants were recruited from UCL staff and students. |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Study population (n=51) are either patients with symptoms of Long COVID who have been referred for clinical investigation (with or without severe exercise impairment) or healthy controls.
Key inclusion criteria (2 listed)
- Serological or clinical diagnosis of CoV-2 infection
- Ability to provide written informed consent.
Key exclusion criteria (8 listed)
- < 18 years old.
- Considered a vulnerable adult
- Participant unwilling to consent
- Terminal illness or severe comorbidities affecting attendance or study investigations
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Pulmonary function (spirometry)
Time frame: Baseline
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.
Cardiac function (echocardiography)
Time frame: Baseline
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.
Microvascular function (microvascular reactivity)
Time frame: Baseline
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.
Macrovascular function (central BP)
Time frame: Baseline
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.
Skeletal muscle oxidative capacity
Time frame: Baseline
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.
1 secondary outcome
Change in cardiorespiratory fitness (VO2max)
Time frame: Baseline and 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2023.
- Background: PubMed 31820039Jones 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.
- Background: PubMed 24383418Jones 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.
- Background: PubMed 17136973Casaburi 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.
- Derived from this study: PubMed 38346773Jamieson A, Al Saikhan L, Alghamdi L, Hamill Howes L, Purcell H, Hillman T, Heightman M, Treibel T, Orini M, Bell R, Scully M, Hamer M, Chaturvedi N, Montgomery H, Hughes AD, Astin R, Jones S. Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction. Physiol Rep. 2024 Feb;12(3):e15940. doi: 10.14814/phy2.15940.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Professor Hughes principal investigator
UCL, University College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of COVID-19, run by University College, London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulmonary function (spirometry) (time frame: Baseline). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04914754, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2023.