Exhaled Breath Olfactory Signature of Pulmonary Arterial Hypertension (SNOOPY2)

• ClinicalTrials.gov Identifier: NCT02782026
• Recruitment Status: Unknown
• First Posted: May 25, 2016
• Last Update Posted: October 2, 2017
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Technion, Israel Institute of Technology; Bayer
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

In this prospective case-control study, the investigators will evaluate the diagnostic performance of a novel electronic nose (E-nose) for the detection of Pulmonary Arterial Hypertension (PAH). This study is designed to:

1. Assess the performance of the E-nose to discriminate controls from patients with PAH
2. Assess the performance of the E-nose to discriminate between different subtypes of pulmonary hypertension (PH), namely idiopathic PAH, heritable PAH with BMPR2 mutation and chronic thromboembolic PH
3. Assess the performance of the E-nose to discriminate controls from asymptomatic patients with PH who carry BMPR2 mutations.

Condition or disease	Intervention/treatment	Phase
Pulmonary Hypertension	Device: Exhaled Breath Olfactory Signature (Artificial Nose)	Not Applicable

Detailed Description:

Pulmonary arterial hypertension (PAH) is a progressive and rare severe disease (prevalence of 15-50 per million) due to obstruction of small pulmonary arteries, leading to an increase in pulmonary artery pressure with the ultimate consequence right heart failure. Despite recent advances in therapeutic care, there is no cure and most patients die or require lung transplantation within 5 years of diagnosis. Currently, right heart catheterisation is required to diagnose PAH and monitor response to treatment. Right heart catheterisation is an invasive test, and alternatives such as echocardiography have not yielded sufficient accuracy both for early diagnosis and disease monitoring. Currently, PAH is often diagnosed at an advanced stage of the disease. There is often a delay in diagnosis of several years between the first symptoms and the identification of the disease due to the non-specific nature of symptoms. Hence, there is the need to improve the time between the first signs and definitive diagnosis of the disease. Early diagnosis of PAH remains a challenge due to the low sensitivity and specificity of biomarkers available currently.

The main objective is to validate the results obtained in the previous preliminary proof of concept study - that PAH patients display a unique olfactory signature that can be detected by an artificial E- nose.

Secondary objectives are to investigate the ability of the E-nose to:

• Discriminate patients with idiopathic PAH from those with heritable PAH due to BMPR2 mutations
• Discriminate patients with chronic thromboembolic pulmonary hypertension (CTEPH) from healthy controls, and patients with idiopathic and/or heritable PAH.
• Detect development of PAH in BMPR2 mutation carriers
• Determine whether the olfactory signature can stratify subgroups of patients by correlating the olfactory signature to different biological and clinical parameters (hemodynamic measurements, NYHA class, duration of treatment, 6-minute walk distance, response to nitric oxide, BNP levels).

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 350 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Exhaled Breath Olfactory Signature of Pulmonary Arterial Hypertension Detected by an Artificial Nose: A Clinical Validation Study
• Study Start Date: March 2016
• Estimated Primary Completion Date: September 2018
• Estimated Study Completion Date: September 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: idiopathic PAH; Exhaled Breath Olfactory Signature Detected by an Artificial Nose	Device: Exhaled Breath Olfactory Signature (Artificial Nose)
Experimental: heritable PAH with BMPR2 mutation; Exhaled Breath Olfactory Signature Detected by an Artificial Nose	Device: Exhaled Breath Olfactory Signature (Artificial Nose)
Experimental: chronic thromboembolic PH; Exhaled Breath Olfactory Signature Detected by an Artificial Nose	Device: Exhaled Breath Olfactory Signature (Artificial Nose)
Experimental: Controls; Exhaled Breath Olfactory Signature Detected by an Artificial Nose	Device: Exhaled Breath Olfactory Signature (Artificial Nose)

Outcome Measures

Primary Outcome Measures :

1. Volatile organic compounds in exhaled breath in patients of each group detected using sensor array on the basis of cross-reactive gold-nanoparticles coated with organic ligands. [ Time Frame: Up to 4 hours ]
   The primary endpoint will be the ability of the E-nose to discriminate patients with PAH from healthy controls by their olfactory signature from the profile of volatile organic compounds in exhaled breath.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Patients group

• Age 18 to 65 years inclusive
• Idiopathic or heritable PAH confirmed by right heart catheterization
• Patients with CTEPH confirmed by right heart catheterization

Healthy control group:

• Age 18 to 65 years inclusive
• No known allergy
• No history of known pathology
• Not genetically linked with the patient

At risk group:

• Subjects included in the protocol Delphi2

Exclusion Criteria:

Patients group:

Any of the following:

• Connective tissue disease
• Infection with HIV
• Portal hypertension or liver disease
• Congenital Heart Disease
• Asthma and other coexisting lung disease

Healthy control group:

• Pregnant or breastfeeding woman
• Addiction to alcohol
• Tabacco addiction

Contacts and Locations

Contacts

Contact: Marc Humbert, MD,PhD; +33 140942512; marc.humbert@bct.aphp.fr

Locations

France

AP-HP, Bicêtre Hospital; Recruiting

Le Kremlin-Bicêtre, France, 94275

Contact: Marc Humbert, MD, PhD +33 1 45217972 marc.humbert@bct.aphp.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Technion, Israel Institute of Technology

Bayer

Investigators

• Principal Investigator: Marc Humbert, MD,PhD; Assistance Publique - Hôpitaux de Paris

More Information

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT02782026
• Other Study ID Numbers: 2014-01321-46
• First Posted: May 25, 2016
• Last Update Posted: October 2, 2017
• Last Verified: December 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

pulmonary hypertension; early detection

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases