<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/NCT02196376</url>
  </required_header>
  <id_info>
    <org_study_id>140671</org_study_id>
    <nct_id>NCT02196376</nct_id>
  </id_info>
  <brief_title>Assessment of Antibodies and Inflammatory Markers in Postural Tachycardia Syndrome</brief_title>
  <official_title>Assessment of Antibodies and Inflammatory Markers in Postural Tachycardia Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this pilot study, the investigators will test the hypothesis that patients with postural&#xD;
      tachycardia syndrome will have an elevated percentage of functional antibodies to adrenergic&#xD;
      receptors compared with control subjects without POTS. The investigators further hypothesize&#xD;
      that the percentage of POTS patients with antibodies will be higher in those patients with a&#xD;
      viral infection at the onset of their illness than in those patients with other or undefined&#xD;
      illness onsets.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Postural orthostatic tachycardia syndrome is poorly understood. Many of these patients have&#xD;
      elevated levels of plasma norepinephrine, particularly when upright One subgroup of patients&#xD;
      has a primary hyperadrenergic state. The majority of patients have a marked deficit in plasma&#xD;
      blood volume compared to healthy control subjects. The investigators have previously reported&#xD;
      that some patients suffer paradoxically from a partial dysautonomia affecting the lower&#xD;
      limbs. Most patients seem to suffer from either a primary or secondary increase in central&#xD;
      sympathetic nervous system drive. Recent data have shown that patients with postural&#xD;
      orthostatic tachycardia syndrome have a lower cardiac stroke volume than their healthy&#xD;
      counterparts and this low stroke volume may drive their orthostatic tachycardia.&#xD;
&#xD;
      The investigators plan to do the following:&#xD;
&#xD;
      The physical examination will include (at minimum):&#xD;
&#xD;
        -  Height&#xD;
&#xD;
        -  Weight&#xD;
&#xD;
        -  Orthostatic vital signs (heart rate and blood pressure) Supine and Standing for up to 10&#xD;
           minutes&#xD;
&#xD;
        -  Beighton Criteria for Joint Hypermobility Syndrome (Ehlers-Danlos III)&#xD;
&#xD;
        -  Dependent acrocyanosis (during stand test)&#xD;
&#xD;
      Continuous Heart Rate and Blood Pressure Recording A subset of subjects will be given the&#xD;
      opportunity to also have continuous recordings of heart rate and blood pressure for 5-10&#xD;
      minutes while lying down quietly. They will be instrumented with EKG patches on their body&#xD;
      and a finger blood pressure cuff, and these data will be digitally sampled and acquired on a&#xD;
      dedicated laptop computer for later offline analysis.&#xD;
&#xD;
      There will be an optional rider on the consent form to allow the patient to consent to this&#xD;
      portion of the study.&#xD;
&#xD;
      Blood work&#xD;
&#xD;
      Blood will be drawn for future assay and analysis of the following tests:&#xD;
&#xD;
        -  Antibodies regulating cardiovascular function&#xD;
&#xD;
           o The clinical significance of these antibodies is unknown. The investigators will share&#xD;
           the results of the antibody panel with the subject, but with the caveat that no clinical&#xD;
           interpretation or comment on significance can be made.&#xD;
&#xD;
        -  Inflammatory markers&#xD;
&#xD;
      The total amount of blood drawn for this project will be less than 15 ml.&#xD;
&#xD;
      Questionnaires&#xD;
&#xD;
        -  RAND-36&#xD;
&#xD;
        -  Health Thermometer&#xD;
&#xD;
        -  Chandler Fatigue Scale&#xD;
&#xD;
        -  Daily diary of Fatigue Symptoms - Fibromyalgia&#xD;
&#xD;
        -  Pain Detect Questionnaire&#xD;
&#xD;
        -  Orthostatic Grading Scale&#xD;
&#xD;
        -  COMPASS-31&#xD;
&#xD;
        -  Structured History (including some of the elements from section 6.1)&#xD;
&#xD;
      These questionnaires will be completed directly online (web-based interface) using a&#xD;
      personalized link that will be provided to the subjects after they give their informed&#xD;
      consent. These will be created in a REDCap-Survey environment, with the data collected and&#xD;
      stored on a password-protected, HIPAA-compliant, secure computer server.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Anticipated">July 2025</completion_date>
  <primary_completion_date type="Anticipated">July 2025</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Ab titer in POTS patients compared to control subjects</measure>
    <time_frame>One time only, at first visit</time_frame>
    <description>The primary outcome measure will be the proportion of subjects with alpha-1 Ab titer. The primary comparison will be the proportion of Ab titers between POTS patients compared to control subjects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>comparison of the number of POTS patients with viral based Ab versus non-viral based Ab</measure>
    <time_frame>One time only - at first study visit</time_frame>
    <description>Blood samples will be collected at study visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison of the number of POTS patients with and without Ehlers Danlos syndrome III</measure>
    <time_frame>One time only - at first study visit</time_frame>
    <description>Ehlers Danlos Syndrome will be assessed during the physical exam. The hypermobility assessment (Beighton Score) will be used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison of the number of POTS patients with a history of autoimmune disorders versus no history of auto-immune disorders</measure>
    <time_frame>One time only - at first study visit</time_frame>
    <description>History of auto-immune disorders will be collected during the history and physical performed by the physician.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison of the number of POTS patients with fatigue versus no history of fatigue based on severity of impact on normal daily activities.</measure>
    <time_frame>One time only - at first study visit</time_frame>
    <description>Fatigue will be assessed using the RAND-36 Health Thermometer Chalder Scale of Fatigue, and Daily Diary of Fatigue.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison of pain in POTS patients versus non-POTS patients</measure>
    <time_frame>One time only - at first study visit</time_frame>
    <description>Pain will be assessed using Fibromyalgia Pain Detect Questionnaire, Orthostatic Grading Scale and COMPASS-31.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">212</enrollment>
  <condition>Postural Orthostatic Tachycardia Syndrome</condition>
  <arm_group>
    <arm_group_label>orthostatic tachycardia syndrome</arm_group_label>
    <description>participants with postural orthostatic tachycardia syndrome</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control subjects</arm_group_label>
    <description>participants not diagnosed with postural orthostatic tachycardia syndrome</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>History</intervention_name>
    <description>the physician / PI will conduct a history that may include: demographics Framingham risk factors metabolic diseases inflammatory diseases autoimmune disorders review of medications date of last menstrual period (females) family history of autonomic disorders Onset of postural orthostatic tachycardia syndrome</description>
    <arm_group_label>control subjects</arm_group_label>
    <arm_group_label>orthostatic tachycardia syndrome</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Physical</intervention_name>
    <description>the physical exam will include: height weight orthostatic vitals (heart rate and blood pressure), supine and standing for up to 10 minutes.&#xD;
Beighton Criteria for Join Hypermobility Syndrome Dependent acrocyanosis</description>
    <arm_group_label>control subjects</arm_group_label>
    <arm_group_label>orthostatic tachycardia syndrome</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>blood draw</intervention_name>
    <description>blood will be drawn for: antibodies regulating cardiovascular function inflammatory markers&#xD;
no more than 15 ml (1 TBSP) will be drawn.</description>
    <arm_group_label>control subjects</arm_group_label>
    <arm_group_label>orthostatic tachycardia syndrome</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>The questionnaires will be completed directly online (web-based interface) using a personalized link that will be provided to the subjects after they give their informed consent. These will be created in a REDCap-Survey environment, with the data collected and stored on a password-protected, HIPAA-compliant, secure computer server.&#xD;
The following questionnaires will be conducted:&#xD;
RAND-36 Health Thermometer Chalder Fatigue Scale Daily diary of Fatigue Symptoms - Fibromyalgia Pain Detect Questionnaire Orthostatic Grading Scale COMPASS-31</description>
    <arm_group_label>control subjects</arm_group_label>
    <arm_group_label>orthostatic tachycardia syndrome</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood will be drawn for future assay and analysis of the following tests:&#xD;
&#xD;
      Antibodies regulating cardiovascular function&#xD;
&#xD;
      The clinical significance of these antibodies is unknown. We will share the results of the&#xD;
      antibody panel with the subject, but with the caveat that no clinical interpretation or&#xD;
      comment on significance can be made.&#xD;
&#xD;
      Inflammatory markers&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Chronic orthostatic intolerance, sometimes known as the postural tachycardia syndrome&#xD;
        (POTS), is the most common disorder among patients seen at several centers specializing in&#xD;
        diseases of the autonomic nervous system.&#xD;
&#xD;
        excessive increase in heart rate [&gt;30 min-1] on standing associated with orthostatic&#xD;
        symptoms [including palpitation, chest pain syndrome, dyspnea on standing, mental clouding&#xD;
        and difficulties with concentration], in the absence of orthostatic hypotension.&#xD;
        Orthostatic tachycardia can produce substantial disability among otherwise healthy people.&#xD;
        Patients typically feel tired and run down. Many also report a myriad of symptoms that are&#xD;
        hard to categorize, often involving fatigue. We and others have reported that patients had&#xD;
        a diminished quality of life.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Postural Tachycardia Syndrome&#xD;
&#xD;
          -  Previously diagnosed with POTS&#xD;
&#xD;
          -  Control Subjects&#xD;
&#xD;
          -  Not diagnosed with POTS&#xD;
&#xD;
          -  Age between 13-80 years&#xD;
&#xD;
          -  Male and female subjects are eligible.&#xD;
&#xD;
          -  Able and willing to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to give, or withdrawal of, informed consent&#xD;
&#xD;
          -  Other factors which in the investigator's opinion would prevent the subject from&#xD;
             completing the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Satish Raj, MD, MSCI</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <last_update_submitted>September 12, 2022</last_update_submitted>
  <last_update_submitted_qc>September 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University</investigator_affiliation>
    <investigator_full_name>Satish R. Raj</investigator_full_name>
    <investigator_title>Adjunct Associate Professor of Medicine and Pharmacology</investigator_title>
  </responsible_party>
  <keyword>Postural orthostatic syndrome</keyword>
  <keyword>orthostatic intolerance</keyword>
  <keyword>autonomic dysfunction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Postural Orthostatic Tachycardia Syndrome</mesh_term>
    <mesh_term>Tachycardia</mesh_term>
    <mesh_term>Syndrome</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/NCT02196376
org study id: 140671
nct id: NCT02196376
lead sponsor: 
has dmc: No
In this pilot study, the investigators will test the hypothesis that patients with postural
      tachycardia syndrome will have an elevated percentage of functional antibodies to adrenergic
      receptors compared with control subjects without POTS. The investigators further hypothesize
      that the percentage of POTS patients with antibodies will be higher in those patients with a
      viral infection at the onset of their illness than in those patients with other or undefined
      illness onsets.
Postural orthostatic tachycardia syndrome is poorly understood. Many of these patients have
      elevated levels of plasma norepinephrine, particularly when upright One subgroup of patients
      has a primary hyperadrenergic state. The majority of patients have a marked deficit in plasma
      blood volume compared to healthy control subjects. The investigators have previously reported
      that some patients suffer paradoxically from a partial dysautonomia affecting the lower
      limbs. Most patients seem to suffer from either a primary or secondary increase in central
      sympathetic nervous system drive. Recent data have shown that patients with postural
      orthostatic tachycardia syndrome have a lower cardiac stroke volume than their healthy
      counterparts and this low stroke volume may drive their orthostatic tachycardia.

      The investigators plan to do the following:

      The physical examination will include (at minimum):

        -  Height

        -  Weight

        -  Orthostatic vital signs (heart rate and blood pressure) Supine and Standing for up to 10
           minutes

        -  Beighton Criteria for Joint Hypermobility Syndrome (Ehlers-Danlos III)

        -  Dependent acrocyanosis (during stand test)

      Continuous Heart Rate and Blood Pressure Recording A subset of subjects will be given the
      opportunity to also have continuous recordings of heart rate and blood pressure for 5-10
      minutes while lying down quietly. They will be instrumented with EKG patches on their body
      and a finger blood pressure cuff, and these data will be digitally sampled and acquired on a
      dedicated laptop computer for later offline analysis.

      There will be an optional rider on the consent form to allow the patient to consent to this
      portion of the study.

      Blood work

      Blood will be drawn for future assay and analysis of the following tests:

        -  Antibodies regulating cardiovascular function

           o The clinical significance of these antibodies is unknown. The investigators will share
           the results of the antibody panel with the subject, but with the caveat that no clinical
           interpretation or comment on significance can be made.

        -  Inflammatory markers

      The total amount of blood drawn for this project will be less than 15 ml.

      Questionnaires

        -  RAND-36

        -  Health Thermometer

        -  Chandler Fatigue Scale

        -  Daily diary of Fatigue Symptoms - Fibromyalgia

        -  Pain Detect Questionnaire

        -  Orthostatic Grading Scale

        -  COMPASS-31

        -  Structured History (including some of the elements from section 6.1)

      These questionnaires will be completed directly online (web-based interface) using a
      personalized link that will be provided to the subjects after they give their informed
      consent. These will be created in a REDCap-Survey environment, with the data collected and
      stored on a password-protected, HIPAA-compliant, secure computer server.
observational model: Case-Only
time perspective: Prospective
measure: Ab titer in POTS patients compared to control subjects
time frame: One time only, at first visit
description: The primary outcome measure will be the proportion of subjects with alpha-1 Ab titer. The primary comparison will be the proportion of Ab titers between POTS patients compared to control subjects.
measure: comparison of the number of POTS patients with viral based Ab versus non-viral based Ab
time frame: One time only - at first study visit
description: Blood samples will be collected at study visit.
measure: comparison of the number of POTS patients with and without Ehlers Danlos syndrome III
time frame: One time only - at first study visit
description: Ehlers Danlos Syndrome will be assessed during the physical exam. The hypermobility assessment (Beighton Score) will be used.
measure: comparison of the number of POTS patients with a history of autoimmune disorders versus no history of auto-immune disorders
time frame: One time only - at first study visit
description: History of auto-immune disorders will be collected during the history and physical performed by the physician.
measure: comparison of the number of POTS patients with fatigue versus no history of fatigue based on severity of impact on normal daily activities.
time frame: One time only - at first study visit
description: Fatigue will be assessed using the RAND-36 Health Thermometer Chalder Scale of Fatigue, and Daily Diary of Fatigue.
measure: comparison of pain in POTS patients versus non-POTS patients
time frame: One time only - at first study visit
description: Pain will be assessed using Fibromyalgia Pain Detect Questionnaire, Orthostatic Grading Scale and COMPASS-31.
arm group label: orthostatic tachycardia syndrome
description: participants with postural orthostatic tachycardia syndrome
arm group label: control subjects
description: participants not diagnosed with postural orthostatic tachycardia syndrome
intervention type: Other
intervention name: History
description: the physician / PI will conduct a history that may include: demographics Framingham risk factors metabolic diseases inflammatory diseases autoimmune disorders review of medications date of last menstrual period (females) family history of autonomic disorders Onset of postural orthostatic tachycardia syndrome
arm group label: control subjects
arm group label: orthostatic tachycardia syndrome
intervention type: Other
intervention name: Physical
description: the physical exam will include: height weight orthostatic vitals (heart rate and blood pressure), supine and standing for up to 10 minutes.
Beighton Criteria for Join Hypermobility Syndrome Dependent acrocyanosis
arm group label: control subjects
arm group label: orthostatic tachycardia syndrome
intervention type: Other
intervention name: blood draw
description: blood will be drawn for: antibodies regulating cardiovascular function inflammatory markers
no more than 15 ml (1 TBSP) will be drawn.
arm group label: control subjects
arm group label: orthostatic tachycardia syndrome
intervention type: Behavioral
intervention name: Questionnaires
description: The questionnaires will be completed directly online (web-based interface) using a personalized link that will be provided to the subjects after they give their informed consent. These will be created in a REDCap-Survey environment, with the data collected and stored on a password-protected, HIPAA-compliant, secure computer server.
The following questionnaires will be conducted:
RAND-36 Health Thermometer Chalder Fatigue Scale Daily diary of Fatigue Symptoms - Fibromyalgia Pain Detect Questionnaire Orthostatic Grading Scale COMPASS-31
arm group label: control subjects
arm group label: orthostatic tachycardia syndrome
Blood will be drawn for future assay and analysis of the following tests:

      Antibodies regulating cardiovascular function

      The clinical significance of these antibodies is unknown. We will share the results of the
      antibody panel with the subject, but with the caveat that no clinical interpretation or
      comment on significance can be made.

      Inflammatory markers
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 13 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Satish Raj, MD, MSCI
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University
investigator full name: Satish R. Raj
investigator title: Adjunct Associate Professor of Medicine and Pharmacology
mesh term: Postural Orthostatic Tachycardia Syndrome
mesh term: Tachycardia
mesh term: Syndrome