<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/NCT01729611</url>
  </required_header>
  <id_info>
    <org_study_id>Tonella1</org_study_id>
    <nct_id>NCT01729611</nct_id>
  </id_info>
  <brief_title>Endothelial Function in Patients With Scleroderma or Cirrhosis With and Without Pulmonary Hypertension</brief_title>
  <official_title>Endothelial Function in Patients With Scleroderma or Cirrhosis With and Without Pulmonary Hypertension</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Pulmonary arterial hypertension (PAH) is a condition characterized by an increased pulmonary&#xD;
      vascular resistance that can lead to right heart failure and death. Several diseases are&#xD;
      known etiologies of PAH including scleroderma and cirrhosis. The presence of PAH in the&#xD;
      context of systemic sclerosis or cirrhosis has a dramatic impact on prognosis and survival of&#xD;
      the connective tissue or liver disease.&#xD;
&#xD;
      Despite advances in the diagnosis of PAH, echocardiography remains a necessary test for&#xD;
      screening PAH in patients with scleroderma or cirrhosis. However, echocardiography is less&#xD;
      than ideal for diagnosing PAH and predicting treatment response. Thus, there is a pressing&#xD;
      need to identify methodologies that can accurately and non-invasively recognize the presence&#xD;
      of PAH in patients with scleroderma and cirrhosis.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
        1. To measure endothelial function and exhaled gases in patients with scleroderma and&#xD;
           cirrhosis. To assess whether they correlate with the presence or the development of PAH.&#xD;
&#xD;
        2. The degree of local (forearm) capillary vasodilation during treprostinil iontophoresis&#xD;
           identifies patients who will develop PAH and in those already diagnosed PAH predicts&#xD;
           response to PAH-specific therapies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with scleroderma are known to have endothelial dysfunction and limited data&#xD;
      suggested an association between the degree of endothelial function in scleroderma and the&#xD;
      presence of PAH. However, these data is preliminary and has not been used to predict response&#xD;
      to PAH-specific therapy or the development of PAH. We will test patients with cirrhosis&#xD;
      because they tend to have PAH in the context of a hyperdynamic instead of a hypodynamic state&#xD;
      as observed in scleroderma and PAH.&#xD;
&#xD;
      Aims:&#xD;
&#xD;
        1. To measure endothelial function and exhaled gases in patients with scleroderma or&#xD;
           cirrhosis to assess whether they correlate with the presence or the development of PAH.&#xD;
&#xD;
        2. To evaluate the degree of endothelial response to local treprostinil iontophoresis and&#xD;
           determine if this test can predict the development of pulmonary hypertension or response&#xD;
           to PAH-specific therapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2013</start_date>
  <completion_date type="Actual">April 2021</completion_date>
  <primary_completion_date type="Actual">March 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Base Line</measure>
    <time_frame>up to 3 months</time_frame>
    <description>Baseline characteristics in patients with and without PAH will be compared using parametric (t-test) and non parametric (Mann-Whitney) tests for continuous data and Chi-square for categorical data.</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">119</enrollment>
  <condition>Pulmonary Hypertension</condition>
  <arm_group>
    <arm_group_label>Scleroderma</arm_group_label>
    <description>60 patients with scleroderma - 30 with and 30 without Pulmonary Arterial Hypertension</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cirrhosis</arm_group_label>
    <description>60 patients with cirrhosis - 30 with and 30 without Pulmonary Arteria Hypertension</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with scleroderma or cirrhosis. These patients may or may not have known PAH or be&#xD;
        on treatment of this condition.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with scleroderma or cirrhosis.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Exclusion criteria include individuals younger than 16, etiologies of PAH other than&#xD;
             scleroderma or cirrhosis.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>17 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adriano Tonelli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Cleveland Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>November 15, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>April 1, 2021</last_update_submitted>
  <last_update_submitted_qc>April 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Adriano Tonelli</investigator_full_name>
    <investigator_title>Staff Physician</investigator_title>
  </responsible_party>
  <keyword>Scleroderma</keyword>
  <keyword>Cirrhosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension, Pulmonary</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Fibrosis</mesh_term>
  </condition_browse>
  <!-- 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/NCT01729611
org study id: Tonella1
nct id: NCT01729611
lead sponsor: 
has dmc: No
Pulmonary arterial hypertension (PAH) is a condition characterized by an increased pulmonary
      vascular resistance that can lead to right heart failure and death. Several diseases are
      known etiologies of PAH including scleroderma and cirrhosis. The presence of PAH in the
      context of systemic sclerosis or cirrhosis has a dramatic impact on prognosis and survival of
      the connective tissue or liver disease.

      Despite advances in the diagnosis of PAH, echocardiography remains a necessary test for
      screening PAH in patients with scleroderma or cirrhosis. However, echocardiography is less
      than ideal for diagnosing PAH and predicting treatment response. Thus, there is a pressing
      need to identify methodologies that can accurately and non-invasively recognize the presence
      of PAH in patients with scleroderma and cirrhosis.

      Hypothesis:

        1. To measure endothelial function and exhaled gases in patients with scleroderma and
           cirrhosis. To assess whether they correlate with the presence or the development of PAH.

        2. The degree of local (forearm) capillary vasodilation during treprostinil iontophoresis
           identifies patients who will develop PAH and in those already diagnosed PAH predicts
           response to PAH-specific therapies.
Patients with scleroderma are known to have endothelial dysfunction and limited data
      suggested an association between the degree of endothelial function in scleroderma and the
      presence of PAH. However, these data is preliminary and has not been used to predict response
      to PAH-specific therapy or the development of PAH. We will test patients with cirrhosis
      because they tend to have PAH in the context of a hyperdynamic instead of a hypodynamic state
      as observed in scleroderma and PAH.

      Aims:

        1. To measure endothelial function and exhaled gases in patients with scleroderma or
           cirrhosis to assess whether they correlate with the presence or the development of PAH.

        2. To evaluate the degree of endothelial response to local treprostinil iontophoresis and
           determine if this test can predict the development of pulmonary hypertension or response
           to PAH-specific therapies.
observational model: Cohort
time perspective: Prospective
measure: Base Line
time frame: up to 3 months
description: Baseline characteristics in patients with and without PAH will be compared using parametric (t-test) and non parametric (Mann-Whitney) tests for continuous data and Chi-square for categorical data.
arm group label: Scleroderma
description: 60 patients with scleroderma - 30 with and 30 without Pulmonary Arterial Hypertension
arm group label: Cirrhosis
description: 60 patients with cirrhosis - 30 with and 30 without Pulmonary Arteria Hypertension
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 17 Years
maximum age: 90 Years
healthy volunteers: No
last name: Adriano Tonelli, MD
role: Principal Investigator
affiliation: The Cleveland Clinic
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Adriano Tonelli
investigator title: Staff Physician
mesh term: Hypertension, Pulmonary
mesh term: Hypertension
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Fibrosis