Clinical trial NCT03819777: Volatile Organic Compounds (VOCs) as a Biomarker in Immune-mediated Pulmonary Arterial Hypertension (PAH)
Official title: Volatile Organic Compounds as a Biomarker in Immune-mediated Pulmonary Arterial Hypertension
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pulmonary Arterial Hypertension
Systemic Sclerosis
Systemic Lupus
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2019-01-29
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: See eligibility criteria

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.


Eligibility criteria: 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

Primary outcomes:
measure: Determining unique inflammatory VOC profiles in exhaled air in three groups of patients: IPAH, PAH-CTD and CTD without PAH.
timeFrame: 3 measurements in 2 weeks
Secondary outcomes:
measure: Correlation between unique inflammatory VOCs to well-established biomarkers of immune activation and inflammation in PAH-CTD and idiopathic PAH.
timeFrame: 1 measurement at baseline
measure: 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.
timeFrame: Changes (Δ, delta) between baseline, 3 months, 6 months, 9 months and 12 months
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
Study officials:
affiliation: Maastricht University Medical Center
name: Pieter van Paassen, PhD
role: PRINCIPAL_INVESTIGATOR
References: