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

Volatile Organic Compounds as a Biomarker in Immune-mediated Pulmonary Arterial Hypertension

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.

Study Overview

• Status: Recruiting
• Conditions: Systemic Sclerosis; Pulmonary Arterial Hypertension; Systemic Lupus

• Study Type: Observational
• Enrollment (Anticipated): 150

Contacts and Locations

• Study Contact: Name: Judith Potjewijd, MD; Phone Number: +31 (0) 433871198; Email: pah.uitademingslucht.int@mumc.nl

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • Recruiting
    • Maastricht University Medical Center
    • Contact: Judith Potjewijd, MD; Phone Number: +31-(0)43-3871198; Email: pah.uitademingslucht.int@mumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

See eligibility criteria

Description

Inclusion Criteria:

1. PAH-CTD patients, inclusion criteria:

   • 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.

2. IPAH patients, inclusion criteria:

   • 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

3. SSc and SLE (CTD) patients without PAH, inclusion criteria:

   • 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Idiopathic PAH
CTD-PAH
CTD without PAH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between unique inflammatory VOCs to well-established biomarkers of immune activation and inflammation in PAH-CTD and idiopathic PAH.	The correlation analysis by means of bivariate (Spearman correlation) and multivariate analysis (canonical correlation analysis) will be performed.	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.	Wilcoxon signed-rank test will be utilized to see if the individual, selective inflammatory VOCs after treatment significantly differ with the baseline measurements.	Changes (Δ, delta) between baseline, 3 months, 6 months, 9 months and 12 months

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Pieter van Paassen, PhD, Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): January 31, 2023

Study Registration Dates

• First Submitted: September 5, 2018
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 29, 2019

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Lung Diseases; Connective Tissue Diseases; Hypertension, Pulmonary; Hypertension; Scleroderma, Systemic; Scleroderma, Diffuse; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: NL57351.068.17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No