<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/NCT02982044</url>
  </required_header>
  <id_info>
    <org_study_id>ASPEN</org_study_id>
    <nct_id>NCT02982044</nct_id>
  </id_info>
  <brief_title>Artery Function Responses to Changes in Blood Flow</brief_title>
  <acronym>ASPEN</acronym>
  <official_title>Endothelial Function Responses to Manipulations in Blood Flow Pattern</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Natural Sciences and Engineering Research Council, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>McMaster University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if different blood flow patterns change artery&#xD;
      function. We hypothesize that the temporary induction of an oscillatory blood flow pattern&#xD;
      will result in an immediate improvement in artery function. Participants will be asked to&#xD;
      come to the Vascular Dynamics Lab (IWC E102) at McMaster University for a total of 3 visits.&#xD;
      The first visit will allow the participant to get comfortable with the lab and the upcoming&#xD;
      tests; and the next 2 visits will be scheduled at the same time of day to collect data. For&#xD;
      visits 2 and 3, participants will be asked to arrive after a 4 hour fast. At these visits,&#xD;
      ultrasound imaging will be used to examine the arteries and how they may change when blood&#xD;
      flow patterns through an artery in the arm are changed. To change blood flow in the arm,&#xD;
      heat, rhythmic squeezing of the forearm with a cuff, or handgrip exercise will be used. These&#xD;
      interventions will be applied to the left forearm, from the elbow to the fingertips. A&#xD;
      trained technician will also draw a blood sample during both data collection visits. A total&#xD;
      of 10 participants will be recruited for the entire study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Interested individuals will be invited to the lab for a screening and familiarization visit,&#xD;
      in which the brachial artery (BA) will be scanned to vet for image quality and a BA&#xD;
      flow-mediated dilation test will be performed to ensure participant tolerance during&#xD;
      collection visits. All qualified participants will be instructed to refrain from vigorous&#xD;
      physical activity &gt; 24 hours, alcohol and caffeine &gt; 6 hours, and food &gt; 4 hours prior to&#xD;
      each of the two collection visits. Upon arrival, basic anthropometric measures will be&#xD;
      collected and hematocrit will be measured in duplicate with a finger prick blood sample&#xD;
      equivalent to two 70 µl capillary tubes. Each of the two data collection visits will begin 10&#xD;
      minutes of supine rest, while the participant is instrumented with skin temperature probes on&#xD;
      the forearms and hands for measurement of skin temperature, single-lead ECG (Powerlab model&#xD;
      ML795, ADInstruments, Colorado Springs, CO, USA) and non-invasive finger cuff (Finometer&#xD;
      MIDI, Finapres, The Netherlands) for continuous heart rate and blood pressure monitoring. On&#xD;
      the first data collection visit, following rest, the participant will then undergo three&#xD;
      10-minute interventions applied to the left forearm in the following sequence: (1) ECG-gated&#xD;
      suprasystolic (300 mmHg) cuff compressions with inflation occurring every other heart cycle,&#xD;
      (2) 42 °C heating with a heating blanket, and (3) ECG-gated rhythmic handgrip exercise at 30%&#xD;
      MVC with contraction occurring every other heart cycle. 10-minute rest periods will separate&#xD;
      each of the interventions to allow for return to baseline conditions. On the second data&#xD;
      collection visit, following rest, the participant will undergo three variations of the&#xD;
      10-minute cuff compression intervention, the order of which will be randomized. The three&#xD;
      variations differ in the trigger delay from the R spike of the ECG to cause inflation of the&#xD;
      cuff for compressions. The original intervention involves the data acquisition unit&#xD;
      triggering inflation of the cuff at systole (R spike) (0s delay). This condition will be&#xD;
      compared to two other trigger delays, specifically triggering inflation of the cuff at 0.2s&#xD;
      and 0.4s after the R spike. For both data collection visits, BA blood velocities, blood flow&#xD;
      turbulence, endothelial shear stress, and oscillatory shear index will be assessed before and&#xD;
      during each of the interventions; and relative flow-mediated dilation will be assessed before&#xD;
      and immediately after each of the interventions. Participants will provide written informed&#xD;
      consent prior to beginning any portion of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">March 2017</completion_date>
  <primary_completion_date type="Actual">March 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Brachial artery flow-mediated dilation</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Collected using vascular ultrasound and analyzed using semi-automated edge-tracking software</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean blood velocity magnitude and direction</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Collected using vascular ultrasound and sent to spectral analyzer for calculation of intensity-weighted mean</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reynolds number (blood flow turbulence)</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Calculated using blood velocity and artery diameter obtained from vascular ultrasound, and blood density and viscosity calculated using hematocrit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial shear stress</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Calculated using blood velocity and artery diameter obtained from vascular ultrasound, and blood viscosity calculated using hematocrit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oscillatory shear index</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Calculated using blood velocity and artery diameter obtained from vascular ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endothelial shear rate</measure>
    <time_frame>Up to 2 weeks</time_frame>
    <description>Calculated using blood velocity and artery diameter obtained from vascular ultrasound</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Endothelial Dysfunction</condition>
  <arm_group>
    <arm_group_label>Experimental-Control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will undergo all interventions, while simultaneously serving as their own within-subject control. The left side of the body will be designated &quot;experimental&quot;, and all interventions will be applied to the left arm. The right side of the body will be designated as &quot;control&quot;, and will not receive any interventions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Suprasystolic (300 mmHg) cuff compressions</intervention_name>
    <description>10 minutes of ECG-gated repeated suprasystolic (300 mmHg) cuff compressions, with inflation occurring every other heart cycle. These cuff compressions may be triggered 0 seconds, 0.2 seconds, or 0.4 seconds from the R spike (systole) on the ECG signal.</description>
    <arm_group_label>Experimental-Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Handgrip exercise</intervention_name>
    <description>10 minutes of ECG-gated rhythmic handgrip exercise at 30% maximal voluntary contraction, with contraction occurring every other heart cycle</description>
    <arm_group_label>Experimental-Control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Passive heat stress</intervention_name>
    <description>10 minutes of passive heat stress at 42 degrees Celsius with a commercially available heating blanket</description>
    <arm_group_label>Experimental-Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy (no cardiovascular, musculoskeletal, or metabolic disease)&#xD;
&#xD;
          -  Male&#xD;
&#xD;
          -  18-35 years old&#xD;
&#xD;
          -  Recreationally active (exercising 2-3 times per week)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiovascular, musculoskeletal, or metabolic disease&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maureen J MacDonald, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McMaster University Vascular Dynamics Lab</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8S 4L8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Wang C, Baker BM, Chen CS, Schwartz MA. Endothelial cell sensing of flow direction. Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2130-6. doi: 10.1161/ATVBAHA.113.301826. Epub 2013 Jun 27.</citation>
    <PMID>23814115</PMID>
  </reference>
  <reference>
    <citation>Tinken TM, Thijssen DH, Hopkins N, Dawson EA, Cable NT, Green DJ. Shear stress mediates endothelial adaptations to exercise training in humans. Hypertension. 2010 Feb;55(2):312-8. doi: 10.1161/HYPERTENSIONAHA.109.146282. Epub 2010 Jan 4.</citation>
    <PMID>20048193</PMID>
  </reference>
  <reference>
    <citation>Thijssen DH, Dawson EA, Black MA, Hopman MT, Cable NT, Green DJ. Brachial artery blood flow responses to different modalities of lower limb exercise. Med Sci Sports Exerc. 2009 May;41(5):1072-9. doi: 10.1249/MSS.0b013e3181923957.</citation>
    <PMID>19346980</PMID>
  </reference>
  <reference>
    <citation>Gurovich AN, Braith RW. Enhanced external counterpulsation creates acute blood flow patterns responsible for improved flow-mediated dilation in humans. Hypertens Res. 2013 Apr;36(4):297-305. doi: 10.1038/hr.2012.169. Epub 2012 Oct 18.</citation>
    <PMID>23076403</PMID>
  </reference>
  <reference>
    <citation>Reneman RS, Arts T, Hoeks AP. Wall shear stress--an important determinant of endothelial cell function and structure--in the arterial system in vivo. Discrepancies with theory. J Vasc Res. 2006;43(3):251-69. doi: 10.1159/000091648. Epub 2006 Feb 20.</citation>
    <PMID>16491020</PMID>
  </reference>
  <reference>
    <citation>Totosy de Zepetnek JO, Ditor DS, Au JS, MacDonald MJ. Impact of shear rate pattern on upper and lower limb conduit artery endothelial function in both spinal cord-injured and able-bodied men. Exp Physiol. 2015 Oct;100(10):1107-17. doi: 10.1113/EP085056. Epub 2015 Aug 18.</citation>
    <PMID>26206681</PMID>
  </reference>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>November 24, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>January 16, 2018</last_update_submitted>
  <last_update_submitted_qc>January 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>blood flow</keyword>
  <keyword>endothelial function</keyword>
  <keyword>shear stress</keyword>
  <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/NCT02982044
org study id: ASPEN
nct id: NCT02982044
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this study is to determine if different blood flow patterns change artery
      function. We hypothesize that the temporary induction of an oscillatory blood flow pattern
      will result in an immediate improvement in artery function. Participants will be asked to
      come to the Vascular Dynamics Lab (IWC E102) at McMaster University for a total of 3 visits.
      The first visit will allow the participant to get comfortable with the lab and the upcoming
      tests; and the next 2 visits will be scheduled at the same time of day to collect data. For
      visits 2 and 3, participants will be asked to arrive after a 4 hour fast. At these visits,
      ultrasound imaging will be used to examine the arteries and how they may change when blood
      flow patterns through an artery in the arm are changed. To change blood flow in the arm,
      heat, rhythmic squeezing of the forearm with a cuff, or handgrip exercise will be used. These
      interventions will be applied to the left forearm, from the elbow to the fingertips. A
      trained technician will also draw a blood sample during both data collection visits. A total
      of 10 participants will be recruited for the entire study.
Interested individuals will be invited to the lab for a screening and familiarization visit,
      in which the brachial artery (BA) will be scanned to vet for image quality and a BA
      flow-mediated dilation test will be performed to ensure participant tolerance during
      collection visits. All qualified participants will be instructed to refrain from vigorous
      physical activity > 24 hours, alcohol and caffeine > 6 hours, and food > 4 hours prior to
      each of the two collection visits. Upon arrival, basic anthropometric measures will be
      collected and hematocrit will be measured in duplicate with a finger prick blood sample
      equivalent to two 70 µl capillary tubes. Each of the two data collection visits will begin 10
      minutes of supine rest, while the participant is instrumented with skin temperature probes on
      the forearms and hands for measurement of skin temperature, single-lead ECG (Powerlab model
      ML795, ADInstruments, Colorado Springs, CO, USA) and non-invasive finger cuff (Finometer
      MIDI, Finapres, The Netherlands) for continuous heart rate and blood pressure monitoring. On
      the first data collection visit, following rest, the participant will then undergo three
      10-minute interventions applied to the left forearm in the following sequence: (1) ECG-gated
      suprasystolic (300 mmHg) cuff compressions with inflation occurring every other heart cycle,
      (2) 42 °C heating with a heating blanket, and (3) ECG-gated rhythmic handgrip exercise at 30%
      MVC with contraction occurring every other heart cycle. 10-minute rest periods will separate
      each of the interventions to allow for return to baseline conditions. On the second data
      collection visit, following rest, the participant will undergo three variations of the
      10-minute cuff compression intervention, the order of which will be randomized. The three
      variations differ in the trigger delay from the R spike of the ECG to cause inflation of the
      cuff for compressions. The original intervention involves the data acquisition unit
      triggering inflation of the cuff at systole (R spike) (0s delay). This condition will be
      compared to two other trigger delays, specifically triggering inflation of the cuff at 0.2s
      and 0.4s after the R spike. For both data collection visits, BA blood velocities, blood flow
      turbulence, endothelial shear stress, and oscillatory shear index will be assessed before and
      during each of the interventions; and relative flow-mediated dilation will be assessed before
      and immediately after each of the interventions. Participants will provide written informed
      consent prior to beginning any portion of the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Brachial artery flow-mediated dilation
time frame: Up to 2 weeks
description: Collected using vascular ultrasound and analyzed using semi-automated edge-tracking software
measure: Mean blood velocity magnitude and direction
time frame: Up to 2 weeks
description: Collected using vascular ultrasound and sent to spectral analyzer for calculation of intensity-weighted mean
measure: Reynolds number (blood flow turbulence)
time frame: Up to 2 weeks
description: Calculated using blood velocity and artery diameter obtained from vascular ultrasound, and blood density and viscosity calculated using hematocrit
measure: Endothelial shear stress
time frame: Up to 2 weeks
description: Calculated using blood velocity and artery diameter obtained from vascular ultrasound, and blood viscosity calculated using hematocrit
measure: Oscillatory shear index
time frame: Up to 2 weeks
description: Calculated using blood velocity and artery diameter obtained from vascular ultrasound
measure: Endothelial shear rate
time frame: Up to 2 weeks
description: Calculated using blood velocity and artery diameter obtained from vascular ultrasound
arm group label: Experimental-Control
arm group type: Experimental
description: Participants will undergo all interventions, while simultaneously serving as their own within-subject control. The left side of the body will be designated "experimental", and all interventions will be applied to the left arm. The right side of the body will be designated as "control", and will not receive any interventions.
intervention type: Other
intervention name: Suprasystolic (300 mmHg) cuff compressions
description: 10 minutes of ECG-gated repeated suprasystolic (300 mmHg) cuff compressions, with inflation occurring every other heart cycle. These cuff compressions may be triggered 0 seconds, 0.2 seconds, or 0.4 seconds from the R spike (systole) on the ECG signal.
arm group label: Experimental-Control
intervention type: Other
intervention name: Handgrip exercise
description: 10 minutes of ECG-gated rhythmic handgrip exercise at 30% maximal voluntary contraction, with contraction occurring every other heart cycle
arm group label: Experimental-Control
intervention type: Other
intervention name: Passive heat stress
description: 10 minutes of passive heat stress at 42 degrees Celsius with a commercially available heating blanket
arm group label: Experimental-Control
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Maureen J MacDonald, PhD
role: Principal Investigator
affiliation: McMaster University
facility: 
country: Canada
citation: Wang C, Baker BM, Chen CS, Schwartz MA. Endothelial cell sensing of flow direction. Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2130-6. doi: 10.1161/ATVBAHA.113.301826. Epub 2013 Jun 27.
PMID: 23814115
citation: Tinken TM, Thijssen DH, Hopkins N, Dawson EA, Cable NT, Green DJ. Shear stress mediates endothelial adaptations to exercise training in humans. Hypertension. 2010 Feb;55(2):312-8. doi: 10.1161/HYPERTENSIONAHA.109.146282. Epub 2010 Jan 4.
PMID: 20048193
citation: Thijssen DH, Dawson EA, Black MA, Hopman MT, Cable NT, Green DJ. Brachial artery blood flow responses to different modalities of lower limb exercise. Med Sci Sports Exerc. 2009 May;41(5):1072-9. doi: 10.1249/MSS.0b013e3181923957.
PMID: 19346980
citation: Gurovich AN, Braith RW. Enhanced external counterpulsation creates acute blood flow patterns responsible for improved flow-mediated dilation in humans. Hypertens Res. 2013 Apr;36(4):297-305. doi: 10.1038/hr.2012.169. Epub 2012 Oct 18.
PMID: 23076403
citation: Reneman RS, Arts T, Hoeks AP. Wall shear stress--an important determinant of endothelial cell function and structure--in the arterial system in vivo. Discrepancies with theory. J Vasc Res. 2006;43(3):251-69. doi: 10.1159/000091648. Epub 2006 Feb 20.
PMID: 16491020
citation: Totosy de Zepetnek JO, Ditor DS, Au JS, MacDonald MJ. Impact of shear rate pattern on upper and lower limb conduit artery endothelial function in both spinal cord-injured and able-bodied men. Exp Physiol. 2015 Oct;100(10):1107-17. doi: 10.1113/EP085056. Epub 2015 Aug 18.
PMID: 26206681
responsible party type: Sponsor
sharing ipd: No