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Contact Information:

Dr Emma Hart
+44 (0)117 331 1971
emma.hart@bristol.ac.uk


Dr Hazel Blythe
+44 (0)1173311971
sn18632@bristol.ac.uk


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Be Part of Research - Trial Details - The role of the carotid chemoreflex in long-COVID
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The role of the carotid chemoreflex in long-COVID

Recruiting

Open to: All Genders

Age: Adult

Bristol

Medical Conditions

Long-COVID

This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.


Long-COVID is a condition in which people continue to have health problems for many months or years after a COVID-19 infection. It is a big health and economic problem in the UK, affecting nearly 2 million people and costing ÂŁ8 billion each year. Of these, 71% reported having symptoms for >1 year, 51% >2 years, and 31% for at least 3 years, a prevalence which is worryingly similar to that of March 2023, indicating that incidence is not declining over time. Many people with long-COVID experience ongoing breathing difficulties. They have a pattern of erratic breathing at rest, and during exercise, despite their lung function being normal. It is not currently known why this occurs, but there is increasing evidence that this is due to disruption of the control of breathing, coordinated by the brain and nervous system, rather than a specific lung problem. A key part of this breathing control system is the carotid chemoreflex. This is driven by small organs in the neck called the carotid bodies, which monitor the chemical status of the blood, sending signals into the brain causing breathing and circulatory adjustments. Thus, the carotid chemoreflex controls breathing and feelings of breathlessness. When someone is infected with the COVID-19 virus, the virus enters the carotid bodies and disrupts their normal function, which may explain why some patients with long-COVID are breathless at rest and during exercise. Our recent research shows that the carotid chemoreflex is more sensitive in people with long-COVID, without other health problems.
The aim of this study is to determine whether temporary inactivation of the carotid bodies improves breathing at rest and during exercise in people with long-COVID. We will monitor whether hyperventilation at rest is reduced, and breathing efficiency during exercise is improved when the carotid bodies are inactivated. This study will determine whether the carotid body is a target for future therapeutic treatment for patients with long-COVID and unexplained breathing difficulties.

Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.  

The recruitment start and end dates are as follows:

24 Feb 2025 05 Jan 2027

Three study visits at the Clinical Research Facility, Bristol. Visit 1 is a screening visit and will involve five questionnaires, a 12-lead ECG, lung function tests, urine dipstick and pregnancy tests, height, weight, office blood pressure measurements and a blood sample. Participants will also be sent home with a 24-hour blood pressure monitor. Visits 2 and 3 will be identical, except participants will receive a different infusion (dopamine and saline) each day. The dopamine and saline infusion conditions will be randomised in order. Resting ventilation assessments and hypoxic ventilatory response testing will be completed. A ramped exercise tolerance test will also be performed. Ventilation, blood pressure, oxygen saturation and heart rate will be continuously recorded throughout the visits.


All participants must be 18-75 years old. For the long-COVID group, participants must have a diagnosis of long-COVID and breathlessness that affects their daily lives. For the control group, the participants must have had COVID but symptoms lasted less than 4 weeks, and no breathlessness.

You can take part if:



You may not be able to take part if:


1. Body mass index ≥30 kg/m22. Diagnosed with severe asthma or uncontrolled asthma3. Pregnancy/breastfeeding women4. Ongoing requirement for oxygen therapy 5. Taking antihypertensive, nitrate, steroid or immunosuppressant medication or medication 6. Major illness e.g., cancer, inflammatory disease (including vasculitis) or receiving palliative care7. History of organ transplantation or are candidates for organ transplantation at the time of screening8. History of Chronic Fatigue Syndrome prior to COVID-19 infection9. Diagnosed cardiovascular disease (including current non-benign arrhythmia, chronic heart failure) 10. History of major psychiatric disorder including bipolar disorders, schizophrenia, schizoaffective disorder, major depression11. Diagnosis of structural lung disease (such as COPD or pulmonary fibrosis)12. Diagnosed renal disease13. Congenital or acquired neurological conditions (including dementia), language disorders, repeated or chronic pain conditions (excluding menstrual pain and minor sporadic headaches)14. Diabetes mellitus15. Symptoms of febrile illness 2 weeks before experiment 16. Lower respiratory tract symptoms at time of screening visit17. Excessive alcohol consumption (>28 units/week) or use of illicit drugs18. History of tobacco smoking within the last 12 months19. Inability to understand instructions given in English20. Surgery under general anaesthesia within 3 months21. History of stroke22. Heart transplant23. Coronary revascularisation24. Haemodialysis or peritoneal dialysis25. Participating in another study for an investigational medicinal product26. Known allergy to dopamine


Below are the locations for where you can take part in the trial. Please note that not all sites may be open.

  • University Hospitals Bristol and Weston - Clinical Research Facility
    Clinical Research Facility 60 St Michael's Hill
    Bristol
    BS2 8DX

Benefits: You will get a heart tracing, full blood pressure screen and blood tests, which may be of some benefit from a health check-up point of view; however, these tests should not be relied upon for the identification of undiagnosed medical conditions. Taking part in this study will help us understand more about the science underlying long-COVID, and how the carotid body is involved in it. We want to learn more about the mechanisms of long-COVID, to help identify a treatment to improve some of the symptoms that people with long-COVID experience. Side effects: Venous cannulation: This may cause some discomfort and local bruising. There is a very small chance of a clot forming and infection. The risk is very small as the cannula will not remain in long.
Respiratory (breathing) monitoring: A mask will be fitted that allows us to measure what you are breathing in and out. There are no risks to breathing room air at rest. Dopamine infusion: We will give you a very low dose of dopamine (a drug) which we expect will not give any side effects. We will monitor you closely at all times and if there are any problems with the drug, we will stop the infusion which will stop any problems quickly (within a couple of minutes). This is used commonly in medical practice and is safe at this dose. Dopamine also exists naturally in your body and is a vital chemical messenger in your brain. The dose of dopamine we will use is lower than the routine dose in hospital care. The risk therefore is low. Dopamine is used in the UK for treating cardiogenic shock during a heart attack or during heart surgery because it improves blood flow. The side effects seen at higher doses include feeling and being sick, chest pain, heart racing, fast heart rate, temporary narrowing of blood vessels, low blood pressure, breathlessness, and headache. Very rarely, patients develop a slow heart rate, high blood pressure, injury if the drug leaks into soft tissue, big pupils and abnormal heart rhythms. Given the low dose we are using, we do not expect any side effects. We have used this technique in several other studies, without any problems. Hypoxic ventilatory response testing: Breathing nitrogen can cause some short-lived dizziness or light-headedness. The nitrogen can be immediately switched off and clears from the breathing circuit in seconds. Oxygen levels return to normal quickly after the nitrogen is switched off, and additional oxygen can be given if needed. Bike exercise test: we will ask you to cycle for up to 12 minutes. A research nurse and researcher will be with you at all times, and if you feel unwell, the test can be stopped at any time. The inherent side effects of exhaustive exercise may be experienced.

Dr Emma Hart
+44 (0)117 331 1971
emma.hart@bristol.ac.uk


Dr Hazel Blythe
+44 (0)1173311971
sn18632@bristol.ac.uk



The study is sponsored by University of Bristol and funded by Medical Research Council.



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Read full details for Trial ID: ISRCTN16564696

Or CPMS 65060

Last updated 01 April 2025

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