Volatile Organic Compounds (VOCs) as a Biomarker in Immune-mediated Pulmonary Arterial Hypertension (PAH)

NCT03819777 | Unknown DMC

• 1 other identifier: NL57351.068.17
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Aim: to investigate the role of inflammation and auto-immunity in pulmonary arterial hypertension by using the profile of volatile organic compounds. Hypothesis: first, the investigators hypothesize that at time of diagnosis the VOC profiles will discriminate patients with PAH-CTD and idiopathic PAH (IPAH) from patients with systemic sclerosis or systemic lupus erythematosus (CTD) without PAH, supporting the contention that there is a overlapping inflammatory and auto-immune pathway in PAH. During follow-up, the investigators will measure the VOC profiles of patients in all three groups who will be treated according standard clinical care. The hypothesis is that VOC profiles are affected by therapy.

Conditions

Pulmonary Arterial Hypertension; Systemic Sclerosis; Systemic Lupus

Outcome Measures

Primary Outcomes (1)

• Determining unique inflammatory VOC profiles in exhaled air in three groups of patients: IPAH, PAH-CTD and CTD without PAH.

  Exhaled air samples will be analyzed on inflammatory VOC profiles in the diagnostic phase of the study. Three measurements over a period of two weeks will be done. Statistically analysis will report one average VOC profile of the three measurements. Procedure: the patient is asked to exhale via a sterile mask into the ReCIVA breath sampler (Owlstone Medical, Cambridge, UK) in which mixed total exhaled air is immediately trapped and stored onto stainless-steel two-bed sorption tubes, filled with carbograph 1TD/Carbopack X (Markes International, Wales, UK). The tubes will be analyzed with GC-TOF-MS for the presence of VOCs after which multivariate statistical analysis will be used to select those VOCs unique for the various patient groups.

  3 measurements in 2 weeks

Secondary Outcomes (2)

• Correlation between unique inflammatory VOCs to well-established biomarkers of immune activation and inflammation in PAH-CTD and idiopathic PAH.

  1 measurement at baseline

• Change (Δ, delta) from baseline in selective inflammatory VOC profiles after 3, 6 and 12 months in all patients treated with PAH and/or immunsuppressive medication.

  Changes (Δ, delta) between baseline, 3 months, 6 months, 9 months and 12 months

Study Arms (3)

Idiopathic PAH

CTD-PAH

CTD without PAH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

See eligibility criteria

You may qualify if:

• classification as definite systemic sclerosis or systemic lupus erythematosus according to respectively the ACR-EULAR criteria (16) and SLICC criteria (17)
• minimal age of 18 year
• diagnosis of pulmonary arterial hypertension: mean pulmonary artery pressure (mPAP) of ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and a pulmonary vascular resistance (PVR) ≥240 dynes.s.cm-5 measured by right heart catherization.
• diagnosis of pulmonary arterial hypertension: mean pulmonary artery pressure (mPAP) of ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and a pulmonary vascular resistance (PVR) ≥240 dynes.s.cm-5 measured by right heart catherization.
• no family history of PAH
• triggering factor is excluded: connective tissue disease, drugs or toxins, human immunodeficiency virus, congenital heart disease, portal hypertension, schistosomiasis (2)
• minimal age of 18 year
• classification as definite systemic sclerosis or systemic lupus erythematosus according to respectively the ACR-EULAR criteria (16) and SLICC criteria (17)
• minimal age of 18 year
• no signs of PAH at screening visit

You may not qualify if:

• active or treated malignancy
• tuberculosis or hepatitis B/C infection in case of start immunosuppressive therapy
• need to start immediately with therapy
• already use of immune suppression

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University Medical Center

Maastricht, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

blood exhaled air

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Pieter van Paassen, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Judith Potjewijd, MD

CONTACT

+31 (0) 433871198; pah.uitademingslucht.int@mumc.nl

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2018
• First Posted: January 29, 2019
• Study Start: March 1, 2018
• Primary Completion: October 31, 2022
• Study Completion: January 31, 2023
• Last Updated: September 8, 2021

Record last verified: 2021-08

Locations

NL (1)