Pilot study examining whether gefapixant inhibits the carotid chemoreflex

Heart failure affects over 1 million people in the UK. The prognosis is poor and patients with heart failure often have a reduced quality of life. People with heart failure are more breathless during physical activity, leading to impaired ability to perform daily activities. There are several reasons for this, including overactivity of the carotid body functions. The carotid body, a small organ in the carotid arteries, monitors oxygen levels in the blood and keeps tight control over breathing, heart rate, blood pressure and the sympathetic nervous system (the carotid body chemoreflex). In heart failure, this reflex is known to be oversensitive. Historically we have used dopamine to understand the role of the carotid chemoreflex in human diseases. One issue with dopamine is that it also affects other structures in the body which limits interpretation of results. Recently we have learnt that a specific receptor in the carotid body (the P2X3 receptor) causes overactivity of the carotid chemoreflex in certain diseases including heart failure. Gefapixant is an oral tablet licensed for use in the UK for chronic cough and specifically targets P2X3 receptors. We want to know whether P2X3 blockade via gefapixant reduces chemoreflex sensitivity in healthy humans. We plan to conduct a pilot mechanistic study in healthy adults, to determine whether a single dose of gefapixant can acutely lower carotid body activity and sympathetic nervous activity. We aim to assess this first in a small number of healthy humans, to establish the mechanisms by which P2X3 blockade may reduce carotid body overactivity. We will compare its effect to a control condition using a placebo.