<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/NCT04502225</url>
  </required_header>
  <id_info>
    <org_study_id>200124</org_study_id>
    <nct_id>NCT04502225</nct_id>
  </id_info>
  <brief_title>Effect of Raised Head of the Bed on Lying Blood Pressure in Autonomic Failure</brief_title>
  <official_title>Impact of Decreased Venous Return on Supine Blood Pressure</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Many persons with autonomic failure often have high blood pressure when lying down (supine&#xD;
      hypertension). This study is exploring the impact of decreased venous return to the heart&#xD;
      (achieved by raising the head of the bed) to lessen supine blood pressure. If decreased&#xD;
      venous return to the heart is effective at lowering supine blood pressure, these approaches&#xD;
      may be utilized to treat supine hypertension non-pharmacologically. Raising the head of the&#xD;
      bed decreases the amount of blood returning to the heart due to the effects of gravity. In&#xD;
      this case, the decreased blood return to the heart may decrease blood pressure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autonomic failure (AF) is a severely disabling condition, which is characterized by&#xD;
      orthostatic hypotension (severe drop in blood pressure upon standing), bladder and bowel&#xD;
      dysfunction, and sexual dysfunction. Besides disabling orthostatic hypotension, however, half&#xD;
      of these patients have supine hypertension (high blood pressure when lying). Sustained high&#xD;
      blood pressure is a cardiac risk for heart disease, kidney disease, and stroke. Sustained&#xD;
      supine hypertension during the night induces pressure natriuresis (increased urine production&#xD;
      due to high blood pressure) and volume loss (due to frequent urination/high volumes of&#xD;
      urine), worsening orthostatic hypotension the following morning (blood pressure falls even&#xD;
      more when the blood volume has been decreased due to loss of fluids in urine) and may also&#xD;
      complicate the treatment of orthostatic hypotension with pressor agents (giving a blood&#xD;
      pressure pill to prevent overnight high blood pressure may make daytime standing blood&#xD;
      pressure worse).&#xD;
&#xD;
      Upright posture induces significant gravitational pooling of blood in the lower body that is&#xD;
      normally compensated for by sympathetic activation. Failure of compensatory sympathetic&#xD;
      activation results in orthostatic hypotension in autonomic failure patients due to the&#xD;
      reduction in venous return and cardiac output. This abnormality has been used in autonomic&#xD;
      failure patients with supine hypertension to their benefit by having them sleep with the head&#xD;
      of the bed tilted up. The recommended amount of head up tilt is 10°, or about a 9-inch&#xD;
      elevation of the head of the bed. In the investigators' hands this degree of tilt produces a&#xD;
      significant but only modest decrease in blood pressure. Compliance is a limiting factor&#xD;
      because most patients (and their spouses) are not able to tolerate even this modest level of&#xD;
      head up tilt. Participants often elevate just the torso overnight, but the effect of this&#xD;
      approach on supine blood pressure has not been reported.The investigators would like to&#xD;
      compare the effects of tilt versus only elevating the head on supine blood pressure.&#xD;
&#xD;
      The existing knowledge provides the rationale for the study of the elevation of the head of&#xD;
      the bed as a non-pharmacologic approaches for the treatment of supine hypertension in these&#xD;
      patients. Elevation of the head of the bed will decrease venous return to the heart using the&#xD;
      effects of gravity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 21, 2020</start_date>
  <completion_date type="Anticipated">May 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">May 31, 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 comparison of the effects of two amounts of head elevation (9 and 12 inches) achieved by tilting the bed or raising the head of the bed (up to four comparisons made) on supine blood pressure</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 to 8 AM</time_frame>
    <description>Maximal change from baseline in systolic blood pressure during the night</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Systolic Blood Pressure</measure>
    <time_frame>10 PM to 8 AM or acute session (1 hour at each elevation of the head)</time_frame>
    <description>Difference in systolic blood pressure between tilt and elevated trunk sessions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overnight Urine Volume</measure>
    <time_frame>10 PM to 8 AM</time_frame>
    <description>Comparison of total urinary volume overnight.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">44</enrollment>
  <condition>Supine Hypertension</condition>
  <condition>Autonomic Failure</condition>
  <arm_group>
    <arm_group_label>Elevation of the whole bed (tilt)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tilt of the whole bed so that the participant's head is raised by 9 and/or 12 inches.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Elevation of the trunk</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elevation of the trunk by tilting just the head of the bed so that the participant's head is raised by 9 and/or 12 inches.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Elevation of the whole bed (tilt) - In home</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tilt of the whole bed so that the participant's head is raised by 8 inches.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Elevation of the trunk - In home</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Elevation of the trunk by raising the head 8 inches on a wedge pillow.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tilt</intervention_name>
    <description>Tilt of the whole bed so that the head is elevated by 9 and/or 12 inches in an acute trial or overnight.</description>
    <arm_group_label>Elevation of the whole bed (tilt)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Elevated trunk</intervention_name>
    <description>Elevation of the trunk through raising just the head of the bed until the head is elevated by 9 and/or 12 inches in an acute trial or overnight.</description>
    <arm_group_label>Elevation of the trunk</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Tilt - In home</intervention_name>
    <description>Tilt of the whole bed so that the head is elevated by 8 inches overnight.</description>
    <arm_group_label>Elevation of the whole bed (tilt) - In home</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Elevated Trunk - In home</intervention_name>
    <description>Elevation of the trunk through raising the head 8 inches on a wedge pillow overnight.</description>
    <arm_group_label>Elevation of the trunk - In home</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with autonomic failure and with supine hypertension from all races&#xD;
&#xD;
          -  Males and females, between 18 to 85 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  All medical students&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  High-risk patients (for example: heart failure, symptomatic coronary artery disease,&#xD;
             liver impairment, history of stroke or myocardial infarction)&#xD;
&#xD;
          -  History of serious allergies or asthma.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 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 BSN MPH</last_name>
    <phone>6158751516</phone>
    <email>emily.c.smith@vumc.org</email>
  </overall_contact>
  <location>
    <facility>
      <name>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 BSN MPH</last_name>
    </contact>
    <contact_backup>
      <phone>6158751516</phone>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 20, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pure Autonomic Failure</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/NCT04502225
org study id: 200124
nct id: NCT04502225
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Many persons with autonomic failure often have high blood pressure when lying down (supine
      hypertension). This study is exploring the impact of decreased venous return to the heart
      (achieved by raising the head of the bed) to lessen supine blood pressure. If decreased
      venous return to the heart is effective at lowering supine blood pressure, these approaches
      may be utilized to treat supine hypertension non-pharmacologically. Raising the head of the
      bed decreases the amount of blood returning to the heart due to the effects of gravity. In
      this case, the decreased blood return to the heart may decrease blood pressure.
Autonomic failure (AF) is a severely disabling condition, which is characterized by
      orthostatic hypotension (severe drop in blood pressure upon standing), bladder and bowel
      dysfunction, and sexual dysfunction. Besides disabling orthostatic hypotension, however, half
      of these patients have supine hypertension (high blood pressure when lying). Sustained high
      blood pressure is a cardiac risk for heart disease, kidney disease, and stroke. Sustained
      supine hypertension during the night induces pressure natriuresis (increased urine production
      due to high blood pressure) and volume loss (due to frequent urination/high volumes of
      urine), worsening orthostatic hypotension the following morning (blood pressure falls even
      more when the blood volume has been decreased due to loss of fluids in urine) and may also
      complicate the treatment of orthostatic hypotension with pressor agents (giving a blood
      pressure pill to prevent overnight high blood pressure may make daytime standing blood
      pressure worse).

      Upright posture induces significant gravitational pooling of blood in the lower body that is
      normally compensated for by sympathetic activation. Failure of compensatory sympathetic
      activation results in orthostatic hypotension in autonomic failure patients due to the
      reduction in venous return and cardiac output. This abnormality has been used in autonomic
      failure patients with supine hypertension to their benefit by having them sleep with the head
      of the bed tilted up. The recommended amount of head up tilt is 10°, or about a 9-inch
      elevation of the head of the bed. In the investigators' hands this degree of tilt produces a
      significant but only modest decrease in blood pressure. Compliance is a limiting factor
      because most patients (and their spouses) are not able to tolerate even this modest level of
      head up tilt. Participants often elevate just the torso overnight, but the effect of this
      approach on supine blood pressure has not been reported.The investigators would like to
      compare the effects of tilt versus only elevating the head on supine blood pressure.

      The existing knowledge provides the rationale for the study of the elevation of the head of
      the bed as a non-pharmacologic approaches for the treatment of supine hypertension in these
      patients. Elevation of the head of the bed will decrease venous return to the heart using the
      effects of gravity.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized comparison of the effects of two amounts of head elevation (9 and 12 inches) achieved by tilting the bed or raising the head of the bed (up to four comparisons made) on supine blood pressure
primary purpose: Treatment
masking: None (Open Label)
measure: Systolic Blood Pressure
time frame: 10 PM to 8 AM
description: Maximal change from baseline in systolic blood pressure during the night
measure: Systolic Blood Pressure
time frame: 10 PM to 8 AM or acute session (1 hour at each elevation of the head)
description: Difference in systolic blood pressure between tilt and elevated trunk sessions
measure: Overnight Urine Volume
time frame: 10 PM to 8 AM
description: Comparison of total urinary volume overnight.
arm group label: Elevation of the whole bed (tilt)
arm group type: Experimental
description: Tilt of the whole bed so that the participant's head is raised by 9 and/or 12 inches.
arm group label: Elevation of the trunk
arm group type: Experimental
description: Elevation of the trunk by tilting just the head of the bed so that the participant's head is raised by 9 and/or 12 inches.
arm group label: Elevation of the whole bed (tilt) - In home
arm group type: Experimental
description: Tilt of the whole bed so that the participant's head is raised by 8 inches.
arm group label: Elevation of the trunk - In home
arm group type: Experimental
description: Elevation of the trunk by raising the head 8 inches on a wedge pillow.
intervention type: Other
intervention name: Tilt
description: Tilt of the whole bed so that the head is elevated by 9 and/or 12 inches in an acute trial or overnight.
arm group label: Elevation of the whole bed (tilt)
intervention type: Other
intervention name: Elevated trunk
description: Elevation of the trunk through raising just the head of the bed until the head is elevated by 9 and/or 12 inches in an acute trial or overnight.
arm group label: Elevation of the trunk
intervention type: Other
intervention name: Tilt - In home
description: Tilt of the whole bed so that the head is elevated by 8 inches overnight.
arm group label: Elevation of the whole bed (tilt) - In home
intervention type: Other
intervention name: Elevated Trunk - In home
description: Elevation of the trunk through raising the head 8 inches on a wedge pillow overnight.
arm group label: Elevation of the trunk - In home
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Italo Biaggioni, MD
role: Principal Investigator
affiliation: Vanderbilt University Medical Center
last name: Emily C Smith, RN BSN MPH
phone: 6158751516
email: emily.c.smith@vumc.org
facility: 
status: Recruiting
contact: 
contact backup: 
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: Pure Autonomic Failure
sharing ipd: No