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Breath Analysis in Patients With Suspected Sarcoidosis: The VOCs-IS Study

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Yes
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Participants with Suspected Sarcoidosis:

Inclusion Criteria:

- Age >18 years.

- Suspected pulmonary sarcoidosis undergoing investigations for diagnosis, staging and treatment consideration or discussion at a designated interstitial lung disease multidisciplinary meeting (this includes participants with stage I disease characterised by the presence of hilar or mediastinal lymphadenopathy)
Exclusion Criteria:
- Significant respiratory co-morbidity where the primary major respiratory diagnosis is not sarcoidosis.

- Current smoker or ex-smoker (having ceased smoking <3 months duration) - Extra-pulmonary sarcoidosis without any evidence of pulmonary involvement (characterised by normal pulmonary function tests and no radiological evidence of thoracic sarcoidosis on HRCT or chest radiography) - Inability to provide written consent.

- Self-reported lower respiratory tract infection, or treatment with antibiotics for a lower respiratory tract infection or any other infection within the previous 4 weeks.

Healthy Volunteers:

Inclusion Criteria:

- Age >18 - 70 years.

- Normal spirometry.

Exclusion Criteria:

- Current smoker or ex-smoker (having ceased smoking <3 months duration) - History of uncontrolled diabetes, respiratory, inflammatory gastroenterological, autoimmune or renal disease (characterised by an eGFR <30ml/min/1.73m2) - Self-reported lower respiratory tract infection, or treatment with antibiotics for a lower respiratory tract infection or any other infection within the previous 4 weeks.

- Inability to provide written consent

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04318392
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Manchester University NHS Foundation Trust
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Stephen Fowler, MD FRCP
Principal Investigator Affiliation	The University of Manchester
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United Kingdom
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pulmonary Sarcoidosis

Additional Details

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).

Arms & Interventions

Arms

: Patients with suspected sarcoidosis

Patients presenting with suspected sarcoidosis.

: Healthy controls

Healthy controls matched for age and gender. Recruitment of spouses and partners will also take place where possible.

Interventions

Other: - Breath Analysis

Breath analysis using the ReCIVA device will take place during each study visit.

Other: - Pulmonary Function Tests

Full Pulmonary Function Tests will be performed at baseline and during each study visit if not performed as part of routine clinical care.

Other: - Blood sampling and storage for genetic analysis

Additional voluntary consent will be sought for blood sampling and storage for genetic analysis at baseline.

Other: - Blood sampling and storage of plasma for metabolomic analysis

Blood sampling and storage of plasma for metabolomic analysis will take place during each study visit.

Other: - Bronchoalveolar lavage

Bronchoalveolar lavage will be performed at baseline on all participants undergoing investigation with bronchoscopy or EBUS as part of routine clinical care for investigation of suspected sarcoidosis.

Other: - Sputum Culture

Sputum will be collected during each study visit if the patient can spontaneously expectorate and will be sent for routine microbial analysis as well as metagenomic sequencing.

Other: - Spirometry

Spirometry will be performed on all healthy controls prior to enrolment into the study

Contact a Trial Team

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