<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03819777</url>
  </required_header>
  <id_info>
    <org_study_id>NL57351.068.17</org_study_id>
    <nct_id>NCT03819777</nct_id>
  </id_info>
  <brief_title>Volatile Organic Compounds (VOCs) as a Biomarker in Immune-mediated Pulmonary Arterial Hypertension (PAH)</brief_title>
  <acronym>VOC-PAH</acronym>
  <official_title>Volatile Organic Compounds as a Biomarker in Immune-mediated Pulmonary Arterial Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aim: to investigate the role of inflammation and auto-immunity in pulmonary arterial&#xD;
      hypertension by using the profile of volatile organic compounds.&#xD;
&#xD;
      Hypothesis: first, the investigators hypothesize that at time of diagnosis the VOC profiles&#xD;
      will discriminate patients with PAH-CTD and idiopathic PAH (IPAH) from patients with systemic&#xD;
      sclerosis or systemic lupus erythematosus (CTD) without PAH, supporting the contention that&#xD;
      there is a overlapping inflammatory and auto-immune pathway in PAH. During follow-up, the&#xD;
      investigators will measure the VOC profiles of patients in all three groups who will be&#xD;
      treated according standard clinical care. The hypothesis is that VOC profiles are affected by&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Anticipated">January 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Determining unique inflammatory VOC profiles in exhaled air in three groups of patients: IPAH, PAH-CTD and CTD without PAH.</measure>
    <time_frame>3 measurements in 2 weeks</time_frame>
    <description>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.&#xD;
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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation between unique inflammatory VOCs to well-established biomarkers of immune activation and inflammation in PAH-CTD and idiopathic PAH.</measure>
    <time_frame>1 measurement at baseline</time_frame>
    <description>The correlation analysis by means of bivariate (Spearman correlation) and multivariate analysis (canonical correlation analysis) will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <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.</measure>
    <time_frame>Changes (Δ, delta) between baseline, 3 months, 6 months, 9 months and 12 months</time_frame>
    <description>Wilcoxon signed-rank test will be utilized to see if the individual, selective inflammatory VOCs after treatment significantly differ with the baseline measurements.</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <condition>Systemic Sclerosis</condition>
  <condition>Systemic Lupus</condition>
  <arm_group>
    <arm_group_label>Idiopathic PAH</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>CTD-PAH</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>CTD without PAH</arm_group_label>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood exhaled air&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        See eligibility criteria&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. PAH-CTD patients, inclusion criteria:&#xD;
&#xD;
               -  classification as definite systemic sclerosis or systemic lupus erythematosus&#xD;
                  according to respectively the ACR-EULAR criteria (16) and SLICC criteria (17)&#xD;
&#xD;
               -  minimal age of 18 year&#xD;
&#xD;
               -  diagnosis of pulmonary arterial hypertension: mean pulmonary artery pressure&#xD;
                  (mPAP) of ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and a&#xD;
                  pulmonary vascular resistance (PVR) ≥240 dynes.s.cm-5 measured by right heart&#xD;
                  catherization.&#xD;
&#xD;
          2. IPAH patients, inclusion criteria:&#xD;
&#xD;
               -  diagnosis of pulmonary arterial hypertension: mean pulmonary artery pressure&#xD;
                  (mPAP) of ≥25 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and a&#xD;
                  pulmonary vascular resistance (PVR) ≥240 dynes.s.cm-5 measured by right heart&#xD;
                  catherization.&#xD;
&#xD;
               -  no family history of PAH&#xD;
&#xD;
               -  triggering factor is excluded: connective tissue disease, drugs or toxins, human&#xD;
                  immunodeficiency virus, congenital heart disease, portal hypertension,&#xD;
                  schistosomiasis (2)&#xD;
&#xD;
               -  minimal age of 18 year&#xD;
&#xD;
          3. SSc and SLE (CTD) patients without PAH, inclusion criteria:&#xD;
&#xD;
               -  classification as definite systemic sclerosis or systemic lupus erythematosus&#xD;
                  according to respectively the ACR-EULAR criteria (16) and SLICC criteria (17)&#xD;
&#xD;
               -  minimal age of 18 year&#xD;
&#xD;
               -  no signs of PAH at screening visit&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  active or treated malignancy&#xD;
&#xD;
          -  tuberculosis or hepatitis B/C infection in case of start immunosuppressive therapy&#xD;
&#xD;
          -  need to start immediately with therapy&#xD;
&#xD;
          -  already use of immune suppression&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pieter van Paassen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Judith Potjewijd, MD</last_name>
    <phone>+31 (0) 433871198</phone>
    <email>pah.uitademingslucht.int@mumc.nl</email>
  </overall_contact>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Judith Potjewijd, MD</last_name>
      <phone>+31-(0)43-3871198</phone>
      <email>pah.uitademingslucht.int@mumc.nl</email>
    </contact>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>September 5, 2018</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>September 7, 2021</last_update_submitted>
  <last_update_submitted_qc>September 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Arterial Hypertension</mesh_term>
    <mesh_term>Familial Primary Pulmonary Hypertension</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03819777
org study id: NL57351.068.17
nct id: NCT03819777
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
observational model: Other
time perspective: Prospective
measure: Determining unique inflammatory VOC profiles in exhaled air in three groups of patients: IPAH, PAH-CTD and CTD without PAH.
time frame: 3 measurements in 2 weeks
description: 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.
measure: Correlation between unique inflammatory VOCs to well-established biomarkers of immune activation and inflammation in PAH-CTD and idiopathic PAH.
time frame: 1 measurement at baseline
description: The correlation analysis by means of bivariate (Spearman correlation) and multivariate analysis (canonical correlation analysis) will be performed.
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.
time frame: Changes (Δ, delta) between baseline, 3 months, 6 months, 9 months and 12 months
description: Wilcoxon signed-rank test will be utilized to see if the individual, selective inflammatory VOCs after treatment significantly differ with the baseline measurements.
arm group label: Idiopathic PAH
arm group label: CTD-PAH
arm group label: CTD without PAH
blood exhaled air
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pieter van Paassen, PhD
role: Principal Investigator
affiliation: Maastricht University Medical Center
last name: Judith Potjewijd, MD
phone: +31 (0) 433871198
email: pah.uitademingslucht.int@mumc.nl
facility: 
status: Recruiting
contact: 
country: Netherlands
responsible party type: Sponsor
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
sharing ipd: Undecided