<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/NCT04451850</url>
  </required_header>
  <id_info>
    <org_study_id>2019-1371</org_study_id>
    <nct_id>NCT04451850</nct_id>
  </id_info>
  <brief_title>HRV as a Marker of Treatment Response in PAH Arterial Hypertension</brief_title>
  <official_title>Heart Rate Variability (HRV) as a Marker of Treatment Response in Pulmonary Arterial Hypertension (PAH)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Cincinnati</source>
  <oversight_info>
    <has_dmc>No</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>
      This is a prospective longitudinal cohort study to determine the value of HRV obtained using&#xD;
      noninvasive actigraphy to quantify the response to pulmonary vasodilator therapy in newly&#xD;
      diagnosed PAH patients&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This single center prospective longitudinal cohort study will take place at the University of&#xD;
      Cincinnati (UC). We will screen adult patients newly diagnosed with PAH and placed on&#xD;
      targeted pulmonary vasodilator therapy by their treating physician for enrollment.&#xD;
&#xD;
      We will enroll 35 eligible participants over a two-year period. HRV will be measured using&#xD;
      the Polar™ H10 wearable chest actigraphy device in conjunction with analytic software to&#xD;
      capture HRV data.&#xD;
&#xD;
      After enrollment and completion of the baseline visit, study participants will receive chest&#xD;
      actigraphy device to measure their heart rate for a two hour period twice a week during study&#xD;
      participation. Follow up research visits will be conducted at one-month, 3-months, and&#xD;
      6-months to sync the actigraphy device and assess any AE's.&#xD;
&#xD;
      In-between these visits, study staff will communicate with participants at two weeks, two&#xD;
      months, 4 months, and 5 months, to identify and address any issues with study actigraphic&#xD;
      device, assess any adverse events and maintain regular contact with study participants.&#xD;
&#xD;
      Throughout study participation, subjects will continue routine clinical care at the direction&#xD;
      of their treating physician as needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 1, 2021</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</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>Change from baseline in HRV via RMSSD</measure>
    <time_frame>6 months</time_frame>
    <description>Change from baseline in Root Mean Squared Successive Differences (RMSSD) measure of Heart Rate variability in patients on targeted therapy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in HRV via SDNN</measure>
    <time_frame>6 months</time_frame>
    <description>Change from baseline in Standard Deviation of N-to-N (SDNN) measure of Heart Rate Variability in patients on targeted therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation with Cardiac Magnetic Resonance Imaging Variables</measure>
    <time_frame>6 months</time_frame>
    <description>Correlation between RMSSD and SDNN with key cardiac Magnetic Resonance Imaging Variables of PAH disease, the Right Ventricular Stroke Volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation with NTproBNP</measure>
    <time_frame>6 months</time_frame>
    <description>Correlation between RMSSD and SDNN with N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP), a marker of PAH disease severity and treatment response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation with REVEAL 2.0 Risk Score</measure>
    <time_frame>6 months</time_frame>
    <description>Correlation between RMSSD and SDNN with the REVEAL 2.0 Risk score, a measure of PAH prognosis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation with CAMPHOR Quality of Life Score</measure>
    <time_frame>6 months</time_frame>
    <description>Correlation between RMSSD and SDNN with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) score, a 3-domain quality of life assessment tool specific to PAH patients</description>
  </secondary_outcome>
  <enrollment type="Anticipated">35</enrollment>
  <condition>Pulmonary Arterial Hypertension</condition>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Noninvasive actigraphy monitor</intervention_name>
    <description>Noninvasive chest-mounted actigraphic device to be worn for 2 hour intervals two times per week during the six month study participation.</description>
    <other_name>Polar H10 Heart Rate Monitor</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients seen at the University of Cincinnati PAH Clinic in Cincinnati, Ohio&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All adult patients (ages 18-70) of any functional class with a new diagnosis of PAH&#xD;
             (World health Organization Group 1) placed on targeted therapy&#xD;
&#xD;
          -  Eligible PAH etiologies include idiopathic PAH, associated with connective tissue&#xD;
             disease, human immunodeficiency virus, hereditary, or portopulmonary hypertension&#xD;
&#xD;
          -  Right heart catheterization (RHC) hemodynamics with a mean pulmonary arterial pressure&#xD;
             &gt;=20 millimetres of mercury at rest, a pulmonary capillary wedge pressure &lt;= 15&#xD;
             millimetres of mercury, and a pulmonary vascular resistance &gt;= 3 woods units&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to undergo (non-contrast) Magnetic Resonance Imaging (MRI) testing&#xD;
&#xD;
          -  On chronotropic agents (Beta-Blockers, anti-arrhythmic medications, etc.) that could&#xD;
             affect the calculation and interpretation of HRV measures&#xD;
&#xD;
          -  Conditions that could affect the accuracy of MRI imaging, including a history&#xD;
             previously repaired or unrepaired congenital heart defects, ventricular or atrial&#xD;
             septal defects, or other anatomic cardiac abnormalities)&#xD;
&#xD;
          -  Inability to complete a six-minute walk test&#xD;
&#xD;
          -  Currently being on targeted PAH therapy at the time of consent and enrollment&#xD;
&#xD;
          -  Thyroid disease, known arrhythmias in the past six months, uncontrolled anemia with a&#xD;
             hemoglobin less than 7 grams per deciliter, untreated coronary artery disease or a&#xD;
             diagnosis of myocardial infarction in the past 6 months, the presence of a cardiac&#xD;
             pacemaker&#xD;
&#xD;
          -  Clinically significant lung disease (including pulmonary function testing forced vital&#xD;
             capacity &lt; 60%), a positive ventilation/perfusion scan, uncontrolled sleep apnea not&#xD;
             adherent with noninvasive positive pressure ventilation&#xD;
&#xD;
          -  Unable to consent, pregnant women, and prisoners.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Arun Jose, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Susan McMahan, BSN, RN, CCRP</last_name>
    <phone>513-558-4376</phone>
    <email>susan.mcmahan@uc.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arun Jose, MD, MS</last_name>
      <phone>513-558-7451</phone>
      <email>josean@ucmail.uc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Susan Sellers, BSN, CCRP</last_name>
      <phone>513-558-4376</phone>
      <email>susan.mcmahan@uc.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Heresi GA, Dweik RA. Strengths and limitations of the six-minute-walk test: a model biomarker study in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 May 1;183(9):1122-4. doi: 10.1164/rccm.201012-2079ED. No abstract available.</citation>
    <PMID>21531951</PMID>
  </reference>
  <reference>
    <citation>Ulrich S, Fischler M, Speich R, Bloch KE. Wrist actigraphy predicts outcome in patients with pulmonary hypertension. Respiration. 2013;86(1):45-51. doi: 10.1159/000342351. Epub 2012 Dec 11.</citation>
    <PMID>23234873</PMID>
  </reference>
  <reference>
    <citation>Pugh ME, Buchowski MS, Robbins IM, Newman JH, Hemnes AR. Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension. Chest. 2012 Dec;142(6):1391-1398. doi: 10.1378/chest.12-0150.</citation>
    <PMID>22576635</PMID>
  </reference>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 25, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 30, 2020</study_first_posted>
  <last_update_submitted>October 31, 2022</last_update_submitted>
  <last_update_submitted_qc>October 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>Arun Jose</investigator_full_name>
    <investigator_title>Assistant Professor of Medicine</investigator_title>
  </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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04451850
org study id: 2019-1371
nct id: NCT04451850
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a prospective longitudinal cohort study to determine the value of HRV obtained using
      noninvasive actigraphy to quantify the response to pulmonary vasodilator therapy in newly
      diagnosed PAH patients
This single center prospective longitudinal cohort study will take place at the University of
      Cincinnati (UC). We will screen adult patients newly diagnosed with PAH and placed on
      targeted pulmonary vasodilator therapy by their treating physician for enrollment.

      We will enroll 35 eligible participants over a two-year period. HRV will be measured using
      the Polar™ H10 wearable chest actigraphy device in conjunction with analytic software to
      capture HRV data.

      After enrollment and completion of the baseline visit, study participants will receive chest
      actigraphy device to measure their heart rate for a two hour period twice a week during study
      participation. Follow up research visits will be conducted at one-month, 3-months, and
      6-months to sync the actigraphy device and assess any AE's.

      In-between these visits, study staff will communicate with participants at two weeks, two
      months, 4 months, and 5 months, to identify and address any issues with study actigraphic
      device, assess any adverse events and maintain regular contact with study participants.

      Throughout study participation, subjects will continue routine clinical care at the direction
      of their treating physician as needed.
observational model: Cohort
time perspective: Prospective
measure: Change from baseline in HRV via RMSSD
time frame: 6 months
description: Change from baseline in Root Mean Squared Successive Differences (RMSSD) measure of Heart Rate variability in patients on targeted therapy
measure: Change from baseline in HRV via SDNN
time frame: 6 months
description: Change from baseline in Standard Deviation of N-to-N (SDNN) measure of Heart Rate Variability in patients on targeted therapy
measure: Correlation with Cardiac Magnetic Resonance Imaging Variables
time frame: 6 months
description: Correlation between RMSSD and SDNN with key cardiac Magnetic Resonance Imaging Variables of PAH disease, the Right Ventricular Stroke Volume
measure: Correlation with NTproBNP
time frame: 6 months
description: Correlation between RMSSD and SDNN with N-terminal Pro-B-Type Natriuretic Peptide (NTproBNP), a marker of PAH disease severity and treatment response
measure: Correlation with REVEAL 2.0 Risk Score
time frame: 6 months
description: Correlation between RMSSD and SDNN with the REVEAL 2.0 Risk score, a measure of PAH prognosis
measure: Correlation with CAMPHOR Quality of Life Score
time frame: 6 months
description: Correlation between RMSSD and SDNN with the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) score, a 3-domain quality of life assessment tool specific to PAH patients
intervention type: Other
intervention name: Noninvasive actigraphy monitor
description: Noninvasive chest-mounted actigraphic device to be worn for 2 hour intervals two times per week during the six month study participation.
other name: Polar H10 Heart Rate Monitor
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Arun Jose, MD, MS
role: Principal Investigator
affiliation: University of Cincinnati
last name: Susan McMahan, BSN, RN, CCRP
phone: 513-558-4376
email: susan.mcmahan@uc.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Heresi GA, Dweik RA. Strengths and limitations of the six-minute-walk test: a model biomarker study in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2011 May 1;183(9):1122-4. doi: 10.1164/rccm.201012-2079ED. No abstract available.
PMID: 21531951
citation: Ulrich S, Fischler M, Speich R, Bloch KE. Wrist actigraphy predicts outcome in patients with pulmonary hypertension. Respiration. 2013;86(1):45-51. doi: 10.1159/000342351. Epub 2012 Dec 11.
PMID: 23234873
citation: Pugh ME, Buchowski MS, Robbins IM, Newman JH, Hemnes AR. Physical activity limitation as measured by accelerometry in pulmonary arterial hypertension. Chest. 2012 Dec;142(6):1391-1398. doi: 10.1378/chest.12-0150.
PMID: 22576635
responsible party type: Principal Investigator
investigator affiliation: University of Cincinnati
investigator full name: Arun Jose
investigator title: Assistant Professor of Medicine
mesh term: Pulmonary Arterial Hypertension
mesh term: Familial Primary Pulmonary Hypertension
mesh term: Hypertension
sharing ipd: No