Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT06286163 |
Other study ID # |
PA4099 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
October 1, 2023 |
Est. completion date |
June 30, 2025 |
Study information
Verified date |
February 2024 |
Source |
Imperial College London |
Contact |
Kian Fan Chung, MD |
Phone |
442075947959 |
Email |
f.chung[@]imperial.ac.uk |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
This study is being done in order to understand what causes people to have a chronic cough,
which is defined as a cough lasting for more than 8 weeks. The research team wish to find out
whether there is any inflammation in the lungs of patients with chronic cough. The research
team will also determine whether a suspected chemical produced in the body, called adenosine
triphosphate (ATP) can be responsible for causing the chronic cough. In order to be able to
find out what is abnormal in those who have a chronic cough, The research team will need to
compare their results with those that do not have a chronic cough.
In this study, the research team will examine 10 participants who suffer from chronic cough
and 8 individuals who do not have a chronic cough and are healthy.
Description:
Background to problem Chronic cough is a very common clinical problem that is experienced by
a large number of people and is a condition that can last for many years. It remains a
difficult problem to treat by doctors because there is at present very poor understanding of
what causes this condition of chronic cough. Consequently, the research team do not have much
efficacious treatments for this common condition. Often, a cause for the cough can be
identified by the doctor and treatment of the cause can help reduce or remove the cough. But
in many instances, the cough may not be helped. In many cases also, the cause of the cough is
not identified. These types of cough can be referred as being 'refractory' or 'idiopathic' or
'unexplained'.
Recently, the notion that chronic cough results from a state of hypersensitivity has been put
forward to explain this condition. This has been put forward because those suffering from
chronic cough often report that changes in ambient temperature, laughing, talking on the
phone for more than a few minutes, aerosol sprays, or smoky atmospheres characteristically
trigger bouts of coughing, indicating this state of hypersensitivity as a key common
characteristic in this condition. Furthermore, this state of Cough Hypersensitivity Syndrome
(CHS) could be caused by damage to the nerves (in the lungs and in the brain) by factors
including viral infection, chemicals and inflammation. The nervous system controlling the
sensitivity of the cough is necessarily complex and likely involves various molecules such as
receptors and proteins that increase the sensitivity to cough.
Recently, a blocker of a receptor of a substance called Adenosine triphosphate (ATP),
receptor P2X3, called AF-219 of Gefapixant has been shown to be extremely effective in
suppressing the chronic cough of patients with an idiopathic cough, with a reduction in the
number of coughs by 75% when compared to inactive drug 11. This is a very significant result
because this study would suggest that this ATP receptor, P2X3, may play an important part in
cough hypersensitivity syndrome. ATP is produced by cells and is the source of energy for
cells needed for cellular functions such as movement of the cell and division of the cell.
Indeed, the academic community knows very little about the role of ATP and its receptor,
P2X3, in chronic cough. First, it is possible that ATP may be released in greater amounts in
chronic cough from activated or stressed cells in the airways, including nerves. ATP can
cause inflammation and can be involved in the movement of inflammatory cells, production of
oxygen free radicals by neutrophils and production of cytokines by inflammatory cells. ATP
may induce a neuroimmune inflammatory response that could sensitise the peripheral nerves to
cause this hypersensitivity. Through the PX3R, ATP can cause long-lasting allodynia through
sensitisation of these receptors. Patients with chronic cough cough more to inhaled ATP
compared to healthy subjectsparticipants.
Therefore, The research team want to show that:
1. ATP is released by cough stimuli and stimulates P2X3 receptors in the upper and lower
airways
2. The increased sensory state of the peripheral sensory nerves leads to activation of P2X3
4 Together, these form the basis of cough hypersensitivity syndrome