Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04318392 |
| Other study ID # |
B00081 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2018 |
| Est. completion date |
October 8, 2021 |
Study information
| Verified date |
November 2021 |
| Source |
Manchester University NHS Foundation Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Sarcoidosis is a chronic condition which predominantly affects the lungs and lymph glands
within the chest, however, may affect any organ within the body. At the present time, very
little is known as to the exact cause of sarcoidosis and it is widely believed that the
condition arises due to overreaction of the immune system to an unknown trigger in the
environment such as an infection. Alongside this, the clinical course and progression of the
condition varies considerably; some patients have a very mild form which does require any
specific treatment, where as other patients develop a more severe form which can lead to
permanent scarring (fibrosis) of the lungs if left untreated. At the present time it is
difficult to predict how a patient will be affected by their sarcoidosis as there is a
distinct lack of clinically useful markers which help predict prognosis and identify people
at risk of disease progression or those who require treatment.
The main aims of this study are to use a technique which captures and analyses breath samples
to provide a profile of the chemicals known as volatile organic compounds (VOCs) which are
present in the exhaled breath of patients with sarcoidosis. Specifically the study would look
to see if these VOCs are different in patients with sarcoidosis compared to people who do not
have sarcoidosis or any lung conditions. In addition, the study would look to see how these
breath profiles relate to potential infections, change over time or in response to treatment
with steroids.
The study will involve a total of 80 patients presenting with suspected sarcoidosis and
involve a total of four study visits over the course of twelve months. During each study
visit a sample of breath will be collected alongside a blood test to look for markers of
disease activity as well as completion of two questionnaires relating to a patients degree of
breathlessness and quality of life. At the start of the study an additional questionnaire
will be completed to identify possible risk factors for the development of sarcoidosis as
well as the option of providing a sample of blood for genetic testing (which is voluntary).
In patients undergoing a bronchoscopy or endobronchial ultrasound (EBUS), a sample of fluid
which naturally lines the airways (bronchoalveolar lavage) will also be taken and used for
metagenomic sequencing to try and identify any microbes which might be present within the
lung and airways.
Description:
Sarcoidosis is chronic condition which can affect any organ within the body, however
frequently involves the lungs and thoracic lymph nodes. The exact cause of the disease
remains uncertain and it is thought that the immune system overreacts to a possible inhaled
antigen in the environment. A role has been suggested for triggers such as certain types of
infection.
The clinical course and prognosis of sarcoidosis is extremely variable. Some patients make a
full recovery without the need for any specific treatment, however up to a third of patients
may develop a more severe form of the disease which can lead to scarring and fibrosis of the
lungs. As such, the treatment of sarcoidosis focuses on suppressing the immune system,
however the evidence to support this remains weak. Furthermore, such treatment may place the
patient at risk of long-term side effects.
At the present time, there is a lack of useful markers which not only help diagnose the
condition, but also help to predict and identify those patients at risk of developing more
severe disease or who may require treatment.
The purpose of this study is to use a technique which analyses breath samples to provide a
profile of chemicals which are present in the exhaled breath of patients with sarcoidosis. It
is important to know if this profile differs from healthy people, relates to infections or
changes over time, particularly in response to treatment. As such, hopefully this technique
will provide an alternative way of monitoring the disease or predicting progression.
This is an observational case-control study of patients with suspected sarcoidosis receiving
standard care at two NHS hospitals over the course of 12 months. At baseline, if patients are
undergoing a bronchoscopy or endobronchial ultrasound and lymph node biopsy as part of their
routine clinical care an additional sample of bronchoalveolar lavage fluid will be collected
and used for metagenomic sequencing to identify the presence of any infections such as
bacterial, viruses or fungi. In addition, patients will also be invited to provide additional
voluntary consent for an extra biopsy to be taken which would also be used for metagenomic
sequencing. Alongside this a sample of breath would be collected using the ReCIVA device
(Owlstone Medical, Cambridge, UK), as well as blood sampling and storage for biomarker
analysis. Patients would also be asked to complete three questionnaires including the medical
research council dyspnoea score (MRC) and King's Sarcoidosis Health Related Quality of Life
Questionnaire (KSQ) relating to their employment, level of breathlessness, symptoms and
quality of life. Additional voluntary consent would also be sought for an extra blood test to
be taken at baseline and stored for future genetic analysis.
During the course of study, three further follow-up visits would then take place at 3, 6 and
12 months. During each visit a sputum sample would be collected (if the patient was able to
expectorate spontaneously) as well as repeated blood and breath sampling and completion of
the medical research council dyspnoea score and King's Sarcoidosis Questionnaire. Pulmonary
function tests would be performed as part of routine clinical care. At the end of the study,
a repeat high resolution computerised tomography (CT) scan of the chest would take place to
look for any new changes related to sarcoidosis and assess the activity of the disease.
The study will aim to recruit a total of 80 patients presenting with suspected sarcoidosis
across both sites. In a subset of 10 participants, repeated breath sampling will take place
two weeks from baseline to assess for reproducibility.
Alongside patients with suspected sarcoidosis, 40 healthy volunteers (including partners or
spouses) will be recruited for breath sampling at baseline.
The study is being undertaken as part of a PhD programme and is funded by a grant from
British Lung Foundation. Ethical approval has been granted from the North West - Greater
Manchester Central Research Ethics Committee (IRAS Number 241100).
