Exhaled Breath Analysis Using eNose Technology as a Biomarker for Diagnosis and Disease Progression in Fibrotic ILD

Pulmonary Fibrosis Clinical Trial

— ILDnose  

Official title:

Exhaled Breath Analysis Using eNose Technology as a Biomarker for Diagnosis and Disease Progression in Fibrotic Interstitial Lung Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04680832
• Other study ID #: MEC-2020-0655
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2020
• Est. completion date: December 31, 2026

Study information

• Verified date: March 2024
• Source: Erasmus Medical Center
• Contact: Marlies S Wijsenbeek, MD PhD
• Phone: +31107030323
• Email: m.wijsenbeek-lourens[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ILDnose study a multinational, multicenter, prospective, longitudinal study in outpatients with pulmonary fibrosis. The aim is to assess the accuracy of eNose technology as diagnostic tool for diagnosis and differentiation between the most prevalent fibrotic interstitial lung diseases. The value of eNose as biomarker for disease progression and response to treatment is also assessed. Besides, validity of several questionnaires for pulmonary fibrosis is investigated.

Description:

Patients will be included in the study after signing written informed consent. eNose measurements will take place before or after a routine outpatient clinic visit at the same location as the regular visit, ensuring minimal inconvenience for patients. First, patients will be asked to rinse their mouth thoroughly with water three times. Subsequently, exhaled breath analysis will be performed in duplicate with a 1-minute interval. An eNose measurement consists of five tidal breaths, followed by an inspiratory capacity maneuver to total lung capacity, a five second breath hold, and subsequently a slow expiration (flow <0.4L/s) to residual volume. The measurements are non-invasive and will cost approximately 5-10 minutes in total, including explanation and informed consent procedure. There are no risks associated with this study and the burden for patients is minimal. After the measurement, patients will complete a short survey about questions relevant for the data analysis (food intake in the last two hours, smoking history, medication use, comorbidities, and symptoms of respiratory infection). In addition, patients will complete the L-PF questionnaire and the Global Rating of Change scale (GRoC). The L-PF questionnaire consists of 21 questions on a 5-point Likert scale about the impact of pulmonary fibrosis on quality of life, and takes about 3 minutes to complete. The GRoC consists of one question on a scale from -7 to 7: were there any changes in your quality of life since your last visit? Symptoms (cough and dyspnea) will be scored on a 10 cm VAS scale from -5 to 5. Next to eNose measurements, demographic data and physiological parameters of patients will be collected from the medical records at baseline, month 6, and month 12. Parameters such as age, gender, diagnosis, time since diagnosis, comorbidities, medication, pulmonary function (forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO)), laboratory parameters (i.e. auto-immune antibodies), HRCT pattern, BAL results and if applicable also genetic mutations, will be recorded and stored in an electronic case report form. These parameters will be collected as part of routine daily care, patients will not undergo any additional tests for study purposes. HRCT scans will be re-analysed centrally by an experienced ILD thoracic radiologist. Mortality and lung function parameters will also be collected at 24 months, if this information is available.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients with a diagnosis of fibrotic ILD, as discussed in a multidisciplinary team meeting (50% incident patients and 50% prevalent patients). Patients are classified as 'incident' if they received a diagnosed in a multidisciplinary team meeting within the past six months. Patients will be required to have fibrosis on a HRCT scan <1 year before enrollment in the study defined as reticular abnormality with traction bronchiectasis, with or without honeycombing, as determined by a radiologist. No minimum extent of fibrosis will be required.

Exclusion Criteria:

• Alcohol consumption = 12 hours before the measurement
• Physically not able to perform eNose measurement

Related Conditions & MeSH terms

• Disease Progression
• Pulmonary Fibrosis

Intervention

Diagnostic Test:
• Electronic nose
First, patients will be asked to rinse their mouth thoroughly with water three times. Subsequently, exhaled breath analysis will be performed in duplicate with a 1-minute interval. An eNose measurement consists of five tidal breaths, followed by an inspiratory capacity maneuver to total lung capacity, a five second breath hold, and subsequently a slow expiration (flow <0.4L/s) to residual volume. The measurements are non-invasive and will cost approximately 5-10 minutes in total, including explanation and informed consent procedure. There are no risks associated with this study and the burden for patients is minimal.

Locations

Country	Name	City	State
France	University Lyon 1, Louis Pradel hospital, Lyon. FranceService de pneumologie, hôpital Louis Pradel	Lyon
Germany	Thoraxklinik Heidelberg	Heidelberg
Netherlands	Erasmus MC	Rotterdam
United Kingdom	Royal Brompton Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Countries where clinical trial is conducted

France,  Germany,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diagnostic accuracy for IPF - CHP	Accuracy for differentiating IPF from CHP	Baseline
Primary	AUC for IPF - CHP	AUC for differentiating IPF from CHP	Baseline
Primary	AUC for IPF - iNSIP	AUC for differentiating IPF from iNSIP	Baseline
Primary	Diagnostic accuracy for IPF - iNSIP	Accuracy for differentiating IPF from iNSIP	Baseline
Primary	AUC for IPF - IPAF	AUC for differentiating IPF from IPAF	Baseline
Primary	Diagnostic accuracy for IPF - IPAF	Accuracy for differentiating IPF from IPAF	Baseline
Primary	Diagnostic accuracy for IPF - CTD-ILD	Accuracy for differentiating IPF from CTD-ILD	Baseline
Primary	AUC for IPF - CTD-ILD	AUC for differentiating IPF from CTD-ILD	Baseline
Primary	Diagnostic accuracy for IPF - unclassifiable ILD	Accuracy for differentiating IPF from unclassifiable ILD	Baseline
Primary	AUC for IPF - unclassifiable ILD	AUC for differentiating IPF from unclassifiable ILD	Baseline
Primary	Diagnostic accuracy for CHP - iNSIP	Accuracy for differentiating CHP from iNSIP	Baseline
Primary	AUC for CHP - iNSIP	AUC for differentiating CHP from iNSIP	Baseline
Primary	Diagnostic accuracy for CHP - IPAF	Accuracy for differentiating CHP from IPAF	Baseline
Primary	AUC for CHP - IPAF	AUC for differentiating CHP from IPAF	Baseline
Primary	Diagnostic accuracy for CHP - CTD-ILD	Accuracy for differentiating CHP from CTD-ILD	Baseline
Primary	AUC for CHP - CTD-ILD	AUC for differentiating CHP from CTD-ILD	Baseline
Primary	Diagnostic accuracy for CHP - unclassifiable ILD	Accuracy for differentiating CHP from unclassifiable ILD	Baseline
Primary	AUC for CHP - unclassifiable ILD	AUC for differentiating CHP from unclassifiable ILD	Baseline
Primary	Diagnostic accuracy for iNSIP - IPAF	Accuracy for differentiating iNSIP from IPAF	Baseline
Primary	AUC for iNSIP - IPAF	AUC for differentiating iNSIP from IPAF	Baseline
Primary	Diagnostic accuracy for iNSIP - CTD-ILD	Accuracy for differentiating iNSIP from CTD-ILD	Baseline
Primary	AUC for iNSIP - CTD-ILD	AUC for differentiating iNSIP from CTD-ILD	Baseline
Primary	Diagnostic accuracy for iNSIP - unclassifiable ILD	Accuracy for differentiating iNSIP from unclassifiable ILD	Baseline
Primary	AUC for iNSIP - unclassifiable ILD	AUC for differentiating iNSIP from unclassifiable ILD	Baseline
Primary	Diagnostic accuracy for IPAF - CTD-ILD	Accuracy for differentiating IPAF from CTD-ILD	Baseline
Primary	AUC for IPAF - CTD-ILD	AUC for differentiating IPAF from CTD-ILD	Baseline
Primary	Diagnostic accuracy for IPAF - unclassifiable ILD	Accuracy for differentiating IPAF from unclassifiable ILD	Baseline
Primary	AUC for IPAF - unclassifiable ILD	AUC for differentiating IPAF from unclassifiable ILD	Baseline
Primary	Diagnostic accuracy for CTD-ILD - unclassifiable ILD	Accuracy for differentiating CTD-ILD from unclassifiable ILD	Baseline
Primary	AUC for CTD-ILD - unclassifiable ILD	AUC for differentiating CTD-ILD from unclassifiable ILD	Baseline
Primary	Disease progression	FVC decline in combination with worsening of respiratory symptoms (cough and/or dyspnea) and/or progressive fibrosis on CT scan	12 months after inclusion
Primary	Disease progression	FVC decline in combination with worsening of respiratory symptoms (cough and/or dyspnea) and/or progressive fibrosis on CT scan	24 months after inclusion
Primary	Diagnostic accuracy of disease progression	Relating disease progression (based on FVC decline, CT scan and/or symptoms) to change in eNose values	6 months after inclusion
Primary	Diagnostic accuracy of disease progression	Relating disease progression (based on FVC decline, CT scan and/or symptoms) to change in eNose values	12 months after inclusion
Primary	Diagnostic accuracy of disease progression	Relating disease progression (based on FVC decline, CT scan and/or symptoms) to change in eNose values	24 months after inclusion
Primary	Worsening of respiratory symptoms (cough and/or dyspnea)	Worsening of respiratory symptoms (cough and/or dyspnea) measured on a visual analogue scale (0-10, 0 no symptoms, 10 most severe symptoms)	12 months after inclusion
Primary	Mortality	Deceased subjects	12 months after inclusion
Primary	Mortality	Deceased subjects	24 months after inclusion
Primary	Therapeutic effect	Relating start of anti-fibrotic medication to change in eNose values	6 months after start therapy
Primary	Therapeutic effect	Relating start of anti-fibrotic medication to change in eNose values	12 months after start therapy
Secondary	L-PF evaluation	Relating Longitudinal changes in score of L-PF questionnaire to eNose values	6 months after inclusion
Secondary	L-PF evaluation	Relating Longitudinal changes in score of L-PF questionnaire to lung function values	6 months after inclusion
Secondary	L-PF evaluation	Relating Longitudinal changes in score of L-PF questionnaire to eNose values	12 months after inclusion
Secondary	L-PF evaluation	Relating Longitudinal changes in score of L-PF questionnaire to lung function values	12 months after inclusion
Secondary	L-PF evaluation	Relating Longitudinal changes in score of L-PF questionnaire to eNose values	24 months after inclusion
Secondary	L-PF evaluation	Relating Longitudinal changes in score of L-PF questionnaire to lung function values	24 months after inclusion
Secondary	GRoC evaluation	Relating Longitudinal changes in score of Global Rating of Change Scale to eNose values	6 months after inclusion
Secondary	GRoC evaluation	Relating Longitudinal changes in score of Global Rating of Change Scale to lung function values	6 months after inclusion
Secondary	GRoC evaluation	Relating Longitudinal changes in score of Global Rating of Change Scale to eNose values	12 months after inclusion
Secondary	GRoC evaluation	Relating Longitudinal changes in score of Global Rating of Change Scale to lung function values	12 months after inclusion
Secondary	GRoC evaluation	Relating Longitudinal changes in score of Global Rating of Change Scale to eNose values	24 months after inclusion
Secondary	GRoC evaluation	Relating Longitudinal changes in score of Global Rating of Change Scale to lung function values	24 months after inclusion