<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/NCT03042988</url>
  </required_header>
  <id_info>
    <org_study_id>VR22699</org_study_id>
    <secondary_id>141523</secondary_id>
    <nct_id>NCT03042988</nct_id>
  </id_info>
  <brief_title>Overnight Trials With Heat Stress in Autonomic Failure Patients With Supine Hypertension</brief_title>
  <official_title>Overnight Trials to Compare the Effects of Controlled Heat Stress Versus Sham Control on Nocturnal Supine Hypertension in Autonomic Failure Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Vanderbilt University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Vanderbilt University Medical Center</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with autonomic failure are characterized by disabling orthostatic hypotension (low&#xD;
      blood pressure on standing), and at least half of them also have high blood pressure while&#xD;
      lying down (supine hypertension). Exposure to heat, such as in hot environments, often&#xD;
      worsens their orthostatic hypotension. The causes of this are not fully understood. The&#xD;
      purpose of this study is to evaluate whether applying local heat over the abdomen of patients&#xD;
      with autonomic failure and supine hypertension during the night would decrease their&#xD;
      nocturnal high blood pressure while lying down. This will help us better understand the&#xD;
      mechanisms underlying this phenomenon, and may be of use in the treatment of supine&#xD;
      hypertension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary autonomic failure is a neurodegenerative condition characterized by loss of efferent&#xD;
      sympathetic function and severe baroreflex impairment. The clinical hallmark of autonomic&#xD;
      failure is disabling orthostatic hypotension, but at least half of patients are also&#xD;
      hypertensive while lying down. This supine hypertension can be severe and associated with&#xD;
      end-organ damage and worsening of orthostatic hypotension due to increased pressure&#xD;
      natriuresis. It also complicates the management of these patients by limiting the use of&#xD;
      daytime pressor agents for the treatment of orthostatic hypotension. Currently, no&#xD;
      antihypertensive drug effectively lowers BP and prevents pressure natriuresis without&#xD;
      worsening standing BP.&#xD;
&#xD;
      It is well known that heat exposure (e.g. hot weather or a hot bath or shower) produces an&#xD;
      acute and temporary worsening of orthostatic hypotension in autonomic failure patients.&#xD;
      Factors that may predispose these patients to the lowering BP effects of heat stress include&#xD;
      1) impaired heat dissipation due to inability to sweat, 2) preserved heat-mediated skin&#xD;
      vasodilation, and 3) blunted sympathetic hemodynamic responses to maintain BP (increases in&#xD;
      cardiac output, heart rate, and vaso- and venoconstriction). Our preliminary results showed&#xD;
      that 2 hours of passive heat stress lowers BP in these patients through a decrease in central&#xD;
      volume. In this study, we will assess the efficacy and safety of passive heat stress in the&#xD;
      treatment of nocturnal supine hypertension in autonomic failure patients. Our hypothesis is&#xD;
      that controlled local (abdominal) passive heat stress applied during the night will lower&#xD;
      nocturnal BP in autonomic failure patients with supine hypertension.&#xD;
&#xD;
      To test this hypothesis, we propose to compare the BP effects of passive heat applied during&#xD;
      the night vs. a sham control in a randomized crossover study in autonomic failure patients&#xD;
      with supine hypertension.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 30, 2017</start_date>
  <completion_date type="Anticipated">December 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>randomized, 2-arm crossover study (heat vs sham)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Systolic blood pressure</measure>
    <time_frame>10 pm - 8 am</time_frame>
    <description>Maximal change from baseline in systolic blood pressure during the night, measured from 10 pm to 8 am</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Orthostatic Tolerance the following morning</measure>
    <time_frame>10 min standing</time_frame>
    <description>Orthostatic tolerance defined as the area under the curve of standing systolic blood pressure calculated by the trapezoidal rule (upright systolic blood pressure multiplied by standing time) during a 10-minute standing test</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Hypertension</condition>
  <condition>Pure Autonomic Failure</condition>
  <condition>Multiple System Atrophy</condition>
  <condition>Autonomic Failure</condition>
  <arm_group>
    <arm_group_label>Heat Stress</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Passive heat-stress using a commercial heating pad applied on the trunk</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control (Non-heating)</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Commercial heating pad applied on the trunk but turned off</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Heating pad</intervention_name>
    <description>Heat stress applied on the trunk for up to 8 hours</description>
    <arm_group_label>Heat Stress</arm_group_label>
    <other_name>Local heat stress</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham control</intervention_name>
    <description>heating pad turned off applied on the trunk for up to 8 hours</description>
    <arm_group_label>Control (Non-heating)</arm_group_label>
    <other_name>control</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female patients, between 18-80 yrs., with primary autonomic failure&#xD;
             (Parkinson Disease, Multiple System Atrophy, and Pure Autonomic Failure) and supine&#xD;
             hypertension. Supine hypertension will be defined as SBP≥150 mmHg.&#xD;
&#xD;
          -  Patients able and willing to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Significant cardiac, renal or hepatic illness, or with contraindications to&#xD;
             administration of pressor agents or with other factors, which in the investigator's&#xD;
             opinion would prevent the subject from completing the protocol including clinically&#xD;
             significant abnormalities in clinical, mental or laboratory testing.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Italo Biaggioni, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Vanderbilt University Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emily C Smith, RN</last_name>
    <phone>615.875.1516</phone>
    <email>autonomics@vumc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bonnie K Black, RN</last_name>
    <phone>615-322-3304</phone>
    <email>autonomics@vumc.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Autonomic Dysfunction Center/ Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Emily C Smith, RN</last_name>
      <phone>615-875-1516</phone>
      <email>autonomics@vumc.org</email>
    </contact>
    <contact_backup>
      <last_name>Bonnie K Black, RN</last_name>
      <phone>615-322-3304</phone>
      <email>autonomics@vumc.org</email>
    </contact_backup>
    <investigator>
      <last_name>Bonnie K Black, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Luis E Okamoto, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>David Robertson, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Italo Biaggioni, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Alfredo Gamboa, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Cyndya A Shibao, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Andre Diedrich, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>jorge Celedonio, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Emily C Smith, RN</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>March 17, 2023</last_update_submitted>
  <last_update_submitted_qc>March 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Vanderbilt University Medical Center</investigator_affiliation>
    <investigator_full_name>Italo Biaggioni</investigator_full_name>
    <investigator_title>Professor of Medicine and Pharmacology</investigator_title>
  </responsible_party>
  <keyword>supine hypertension</keyword>
  <keyword>autonomic failure</keyword>
  <keyword>heat stress</keyword>
  <keyword>orthostatic hypotension</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple System Atrophy</mesh_term>
    <mesh_term>Shy-Drager Syndrome</mesh_term>
    <mesh_term>Pure Autonomic Failure</mesh_term>
    <mesh_term>Hypertension</mesh_term>
    <mesh_term>Heat Stress Disorders</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/NCT03042988
org study id: VR22699
secondary id: 141523
nct id: NCT03042988
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Patients with autonomic failure are characterized by disabling orthostatic hypotension (low
      blood pressure on standing), and at least half of them also have high blood pressure while
      lying down (supine hypertension). Exposure to heat, such as in hot environments, often
      worsens their orthostatic hypotension. The causes of this are not fully understood. The
      purpose of this study is to evaluate whether applying local heat over the abdomen of patients
      with autonomic failure and supine hypertension during the night would decrease their
      nocturnal high blood pressure while lying down. This will help us better understand the
      mechanisms underlying this phenomenon, and may be of use in the treatment of supine
      hypertension.
Primary autonomic failure is a neurodegenerative condition characterized by loss of efferent
      sympathetic function and severe baroreflex impairment. The clinical hallmark of autonomic
      failure is disabling orthostatic hypotension, but at least half of patients are also
      hypertensive while lying down. This supine hypertension can be severe and associated with
      end-organ damage and worsening of orthostatic hypotension due to increased pressure
      natriuresis. It also complicates the management of these patients by limiting the use of
      daytime pressor agents for the treatment of orthostatic hypotension. Currently, no
      antihypertensive drug effectively lowers BP and prevents pressure natriuresis without
      worsening standing BP.

      It is well known that heat exposure (e.g. hot weather or a hot bath or shower) produces an
      acute and temporary worsening of orthostatic hypotension in autonomic failure patients.
      Factors that may predispose these patients to the lowering BP effects of heat stress include
      1) impaired heat dissipation due to inability to sweat, 2) preserved heat-mediated skin
      vasodilation, and 3) blunted sympathetic hemodynamic responses to maintain BP (increases in
      cardiac output, heart rate, and vaso- and venoconstriction). Our preliminary results showed
      that 2 hours of passive heat stress lowers BP in these patients through a decrease in central
      volume. In this study, we will assess the efficacy and safety of passive heat stress in the
      treatment of nocturnal supine hypertension in autonomic failure patients. Our hypothesis is
      that controlled local (abdominal) passive heat stress applied during the night will lower
      nocturnal BP in autonomic failure patients with supine hypertension.

      To test this hypothesis, we propose to compare the BP effects of passive heat applied during
      the night vs. a sham control in a randomized crossover study in autonomic failure patients
      with supine hypertension.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: randomized, 2-arm crossover study (heat vs sham)
primary purpose: Treatment
masking: None (Open Label)
measure: Systolic blood pressure
time frame: 10 pm - 8 am
description: Maximal change from baseline in systolic blood pressure during the night, measured from 10 pm to 8 am
measure: Orthostatic Tolerance the following morning
time frame: 10 min standing
description: Orthostatic tolerance defined as the area under the curve of standing systolic blood pressure calculated by the trapezoidal rule (upright systolic blood pressure multiplied by standing time) during a 10-minute standing test
arm group label: Heat Stress
arm group type: Experimental
description: Passive heat-stress using a commercial heating pad applied on the trunk
arm group label: Control (Non-heating)
arm group type: Sham Comparator
description: Commercial heating pad applied on the trunk but turned off
intervention type: Other
intervention name: Heating pad
description: Heat stress applied on the trunk for up to 8 hours
arm group label: Heat Stress
other name: Local heat stress
intervention type: Other
intervention name: Sham control
description: heating pad turned off applied on the trunk for up to 8 hours
arm group label: Control (Non-heating)
other name: control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Italo Biaggioni, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
last name: Emily C Smith, RN
phone: 615.875.1516
email: autonomics@vumc.org
last name: Bonnie K Black, RN
phone: 615-322-3304
email: autonomics@vumc.org
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Vanderbilt University Medical Center
investigator full name: Italo Biaggioni
investigator title: Professor of Medicine and Pharmacology
mesh term: Multiple System Atrophy
mesh term: Shy-Drager Syndrome
mesh term: Pure Autonomic Failure
mesh term: Hypertension
mesh term: Heat Stress Disorders
sharing ipd: No