<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/NCT04499664</url>
  </required_header>
  <id_info>
    <org_study_id>H-19069845</org_study_id>
    <nct_id>NCT04499664</nct_id>
  </id_info>
  <brief_title>Autonomic Cardiovascular Control in Response to Blood Volume Reduction in Blood Donors</brief_title>
  <official_title>Autonomic Cardiovascular Control in Response to Blood Volume Reduction in Blood Donors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hvidovre University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hvidovre University Hospital</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>
      The function of the autonomic nervous system can be assessed using baroreflex sensitivity&#xD;
      (BRS) and heart rate variability (HRV). Decreased HRV has been shown to be predictive of&#xD;
      morbidity and mortality in diverse medical conditions such as acute myocardial infarction,&#xD;
      aneurysmal subarachnoid haemorrhage, autoimmune diseases, sepsis and surgery.&#xD;
&#xD;
      The function of the autonomic nervous system has not yet been investigated in a &quot;pure&#xD;
      hypovolemia&quot; model. The aim of the current study is therefore to investigate and describe the&#xD;
      function of the autonomic nervous system prior to, during and after reduction of blood volume&#xD;
      in healthy blood donors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Actual">June 1, 2022</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</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>Changes in root mean square of successive NN-interval differences (RMSSD) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in root mean square of successive NN-interval differences (RMSSD) during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in standard deviation of N-N intervals (SDNN) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in standard deviation of N-N intervals (SDNN) during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of successive RR intervals that differ by more than 50 ms (pNN50) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of successive RR intervals that differ by more than 50 ms (pNN50) during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in low frequency (LF) power during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms^2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in low frequency (LF) power during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms^2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes high frequency (HF) power during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms^2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes high frequency (HF) power during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms^2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ratio of LF-to-HF power during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ratio of LF-to-HF power during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in S (area of the ellipse which represents total HRV) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in S (area of the ellipse which represents total HRV) during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SD1 (Poincaré plot standard deviation perpendicular the line of identity) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SD1 (Poincaré plot standard deviation perpendicular the line of identity) during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SD2 (Poincaré plot standard deviation along the line of identity) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SD2 (Poincaré plot standard deviation along the line of identity) during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SD1/SD2 ratio during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in SD1/SD2 ratio during sleep</measure>
    <time_frame>The night before and night after blood donation</time_frame>
    <description>Measured in ms</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in systolic arterial pressure (SAP) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in mmHg by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in diastolic arterial pressure (DAP) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in mmHg by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in mean arterial pressure (MAP) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in mmHg by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in pulse pressure (PP) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in mmHg by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in heart rate (HR) during mobilisation</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in beats min-1 by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cardiac output (CO) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in L/min by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in stroke volume (SV) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in mL by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in systemic vascular resistance (SVR) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in dynes s cm-5 by non-invasive LiDCO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cerebral perfusion (ScO2) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in % by Root Masimo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in muscular perfusion (SmO2) during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in % by Root Masimo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in peripheral index during mobilization</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured in % by Root Masimo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of C-reacitve protein</measure>
    <time_frame>At time of blood donation</time_frame>
    <description>Measured in gr/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>V-PLEX Biomarker 54.Plex Kit</measure>
    <time_frame>Blood taken at time of blood donation</time_frame>
    <description>54 key analytes that are important in inflammation response and immune system regulation as well as numerous other biological processes</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Pain score</measure>
    <time_frame>15 minutes prior to and 15 minutes after blood donation</time_frame>
    <description>Measured by verbal rating scale (VRS) 0 - 10 (0 = no pain, 10 = worse pain imaginable) during mobilisation procedure</description>
  </other_outcome>
  <number_of_groups>1</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Autonomic Dysfunction</condition>
  <condition>Autonomic Imbalance</condition>
  <condition>Blood Loss</condition>
  <arm_group>
    <arm_group_label>Blood donors</arm_group_label>
    <description>Healhy young male bloddonors, aged 30-45</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Monitoring of the autonomic nervous system</intervention_name>
    <description>Monitoring of the autonomic nervous system using E-patch, LiDCO and Root-Massimo.</description>
    <arm_group_label>Blood donors</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      10 mL of blood stored in a biobank&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Healthy male volonteers, aged 30-45, that are eligable for blood donation following the&#xD;
        Danish legislation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Volonteers eligable for blood donation following the Danish legislation&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  Age 30-45&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Speak and understand Danish&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Volonteers not eligable for blood donation following the Danish legislation, among others&#xD;
        due to:&#xD;
&#xD;
          -  Alcohol and drug abuse&#xD;
&#xD;
          -  Cognitive dysfunction&#xD;
&#xD;
          -  Use of anxiolytic or antipsychotic drugs&#xD;
&#xD;
          -  Arrhythmias or heart failure&#xD;
&#xD;
          -  Diabetes mellitus type I&#xD;
&#xD;
          -  Diabetes mellitus type II&#xD;
&#xD;
          -  Use of opioids&#xD;
&#xD;
          -  History of following diseases in the autonomic nervous system: Parkinson disease,&#xD;
             multiple sclerosis, autonomic neuropathies&#xD;
&#xD;
          -  History of cerebral apoplexy or transitory cerebral ischemia&#xD;
&#xD;
          -  Dementia&#xD;
&#xD;
          -  American Society of Anesthesiologists (ASA) score ≥ 4&#xD;
&#xD;
        Furthermore:&#xD;
&#xD;
          -  History of orthostatic intolerance and/or orthostatic hypotension&#xD;
&#xD;
          -  Use of following vasodilator antihypertensive drugs: beta-blockers, angiotensin&#xD;
             converting enzyme inhibitors (ACEI), angiotensin 2 receptor blockers (ARBs), calcium&#xD;
             channel blockers&#xD;
&#xD;
          -  Use of loop diuretics, thiazid diuretics and potassium-sparing diuretics&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Henrik Kehlet, Professor</last_name>
    <role>Study Director</role>
    <affiliation>Rigshospitalet, Denmark</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hvidovre University Hospital</name>
      <address>
        <city>Copenhagen</city>
        <zip>2960</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>August 29, 2022</last_update_submitted>
  <last_update_submitted_qc>August 29, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hvidovre University Hospital</investigator_affiliation>
    <investigator_full_name>Ana-Marija Hristovska</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Heart rate variabilty</keyword>
  <keyword>Baroreceptor sensitivity</keyword>
  <keyword>Autonomic nervous system</keyword>
  <keyword>Acute blood loss</keyword>
  <keyword>Blood donors</keyword>
  <keyword>Autonomic cardiovascular control</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autonomic Nervous System Diseases</mesh_term>
    <mesh_term>Primary Dysautonomias</mesh_term>
    <mesh_term>Hemorrhage</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/NCT04499664
org study id: H-19069845
nct id: NCT04499664
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The function of the autonomic nervous system can be assessed using baroreflex sensitivity
      (BRS) and heart rate variability (HRV). Decreased HRV has been shown to be predictive of
      morbidity and mortality in diverse medical conditions such as acute myocardial infarction,
      aneurysmal subarachnoid haemorrhage, autoimmune diseases, sepsis and surgery.

      The function of the autonomic nervous system has not yet been investigated in a "pure
      hypovolemia" model. The aim of the current study is therefore to investigate and describe the
      function of the autonomic nervous system prior to, during and after reduction of blood volume
      in healthy blood donors.
observational model: Cohort
time perspective: Prospective
measure: Changes in root mean square of successive NN-interval differences (RMSSD) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms
measure: Changes in root mean square of successive NN-interval differences (RMSSD) during sleep
time frame: The night before and night after blood donation
description: Measured in ms
measure: Changes in standard deviation of N-N intervals (SDNN) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms
measure: Changes in standard deviation of N-N intervals (SDNN) during sleep
time frame: The night before and night after blood donation
description: Measured in ms
measure: Percentage of successive RR intervals that differ by more than 50 ms (pNN50) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in %
measure: Percentage of successive RR intervals that differ by more than 50 ms (pNN50) during sleep
time frame: The night before and night after blood donation
description: Measured in %
measure: Changes in low frequency (LF) power during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms^2
measure: Changes in low frequency (LF) power during sleep
time frame: The night before and night after blood donation
description: Measured in ms^2
measure: Changes high frequency (HF) power during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms^2
measure: Changes high frequency (HF) power during sleep
time frame: The night before and night after blood donation
description: Measured in ms^2
measure: Changes in ratio of LF-to-HF power during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in %
measure: Changes in ratio of LF-to-HF power during sleep
time frame: The night before and night after blood donation
description: Measured in %
measure: Changes in S (area of the ellipse which represents total HRV) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms
measure: Changes in S (area of the ellipse which represents total HRV) during sleep
time frame: The night before and night after blood donation
description: Measured in ms
measure: Changes in SD1 (Poincaré plot standard deviation perpendicular the line of identity) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms
measure: Changes in SD1 (Poincaré plot standard deviation perpendicular the line of identity) during sleep
time frame: The night before and night after blood donation
description: Measured in ms
measure: Changes in SD2 (Poincaré plot standard deviation along the line of identity) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms
measure: Changes in SD2 (Poincaré plot standard deviation along the line of identity) during sleep
time frame: The night before and night after blood donation
description: Measured in ms
measure: Changes in SD1/SD2 ratio during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in ms
measure: Changes in SD1/SD2 ratio during sleep
time frame: The night before and night after blood donation
description: Measured in ms
measure: Changes in systolic arterial pressure (SAP) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in mmHg by non-invasive LiDCO
measure: Changes in diastolic arterial pressure (DAP) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in mmHg by non-invasive LiDCO
measure: Changes in mean arterial pressure (MAP) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in mmHg by non-invasive LiDCO
measure: Changes in pulse pressure (PP) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in mmHg by non-invasive LiDCO
measure: Changes in heart rate (HR) during mobilisation
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in beats min-1 by non-invasive LiDCO
measure: Changes in cardiac output (CO) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in L/min by non-invasive LiDCO
measure: Changes in stroke volume (SV) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in mL by non-invasive LiDCO
measure: Changes in systemic vascular resistance (SVR) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in dynes s cm-5 by non-invasive LiDCO
measure: Changes in cerebral perfusion (ScO2) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in % by Root Masimo
measure: Changes in muscular perfusion (SmO2) during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in % by Root Masimo
measure: Changes in peripheral index during mobilization
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured in % by Root Masimo
measure: Concentration of C-reacitve protein
time frame: At time of blood donation
description: Measured in gr/dL
measure: V-PLEX Biomarker 54.Plex Kit
time frame: Blood taken at time of blood donation
description: 54 key analytes that are important in inflammation response and immune system regulation as well as numerous other biological processes
measure: Pain score
time frame: 15 minutes prior to and 15 minutes after blood donation
description: Measured by verbal rating scale (VRS) 0 - 10 (0 = no pain, 10 = worse pain imaginable) during mobilisation procedure
arm group label: Blood donors
description: Healhy young male bloddonors, aged 30-45
intervention type: Device
intervention name: Monitoring of the autonomic nervous system
description: Monitoring of the autonomic nervous system using E-patch, LiDCO and Root-Massimo.
arm group label: Blood donors
10 mL of blood stored in a biobank
study pop: 
sampling method: Probability Sample
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Henrik Kehlet, Professor
role: Study Director
affiliation: Rigshospitalet, Denmark
facility: 
country: Denmark
responsible party type: Principal Investigator
investigator affiliation: Hvidovre University Hospital
investigator full name: Ana-Marija Hristovska
investigator title: MD
mesh term: Autonomic Nervous System Diseases
mesh term: Primary Dysautonomias
mesh term: Hemorrhage