<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/NCT02997774</url>
  </required_header>
  <id_info>
    <org_study_id>108616</org_study_id>
    <nct_id>NCT02997774</nct_id>
  </id_info>
  <brief_title>Cooler Dialysis and Liver Perfusion and Function</brief_title>
  <official_title>Evaluation of the Effects of Cooler Dialysate on Liver Perfusion, Endotoxemia and Uremic Toxin Handling in Hemodialysis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chris McIntyre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Lawson Health Research Institute</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>
      Having hemodialysis affects the blood supply to various organs in the body including the&#xD;
      heart and the brain. With time, these effects build up and can affect the way these organs&#xD;
      function. The investigators have previously shown that the liver (a key organ which works to&#xD;
      help clean the blood, make proteins and turn all your food into energy) is also affected. One&#xD;
      of the ways to help protect organs from injury due to dialysis has been cooling during&#xD;
      dialysis. The investigators want to examine whether cooling during dialysis protects the&#xD;
      blood supply to the liver. CT imaging will be used to measure this blood supply during&#xD;
      hemodialysis with standard and cooler settings.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hemodialysis exerts significant hemodynamic effects with widespread consequences on&#xD;
      vulnerable vascular beds. Cardiac injury, including myocardial stunning and subclinical&#xD;
      myocardial ischemia, appears to be common and associated with significantly increased&#xD;
      mortality. The liver has been shown to have preserved blood flow due to its dual blood&#xD;
      supply. Even so, the liver excretory function is decreased and endotoxin levels in the blood&#xD;
      increase during hemodialysis. Extracorporeal cooling during dialysis has been associated with&#xD;
      protective effects on the brain and heart of dialysis patients. The effects of cooler&#xD;
      dialysis on liver perfusion, function and endotoxemia during hemodialysis is unknown.&#xD;
&#xD;
      The investigators therefore propose to use CT perfusion imaging to examine the effect of&#xD;
      cooling during hemodialysis on liver perfusion, relating this effect to endotoxin&#xD;
      translocation and myocardial dysfunction. Additionally, they intend to investigate the&#xD;
      potential effects on hepatic function in this context, examining the relationship between&#xD;
      liver perfusion and endotoxemia, the metabolism of uremic toxins and clinical symptoms of&#xD;
      uremia.&#xD;
&#xD;
      This is a prospective randomized cross-over study involving a single center recruiting&#xD;
      patients from the prevalent dialysis population of London Health Sciences Centre (LHSC) Renal&#xD;
      Program. Once recruited, patients will undergo two study hemodialysis sessions - one will use&#xD;
      standard dialysate temperature of 36.5 degrees Celsius (HD36.5) and one will use cooler&#xD;
      dialysate temperature at 35 degrees Celsius (HD35). The order of these two sessions will be&#xD;
      randomly allocated. Before, during and after each session, participants will undergo cardiac&#xD;
      and hepatic assessment. This will include CT scans, 2D echocardiography and indocyanine green&#xD;
      (ICG) clearance measurements. In addition, participants will answer a number of&#xD;
      questionnaires about uremic symptoms and blood tests will also be done.&#xD;
&#xD;
      The investigators' aim is to characterize and compare liver function and perfusion before&#xD;
      during and after hemodialysis, with standard and cooler dialysate temperature.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2017</start_date>
  <completion_date type="Actual">May 4, 2018</completion_date>
  <primary_completion_date type="Actual">May 4, 2018</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>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>Neither subjects nor the investigator at the study visits will be blinded; however, analysis of imaging data will be performed with the operator blinded to allocation.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in regional liver perfusion in mls/min/100g from baseline to peak stress during dialysis (3 hours into the dialysis session) with standard versus cooler dialysate temperature.</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in global liver perfusion in mls/min/100g pre, during and post-dialysis with cooler dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICG clearance rate pre, during and post-dialysis with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Contribution of portal venous flow to hepatic perfusion (PV fraction) pre, during and post-dialysis with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endotoxin levels with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Troponin T levels with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of stunned myocardial segments with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Uremic toxin levels with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Uremic symptom scores with cooler vs standard dialysate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Haemodialysis Complication</condition>
  <arm_group>
    <arm_group_label>Standard Dialysis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient will undergo dialysis at 36.5 degrees Celsius to assess if this affects the liver function and perfusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cooler Dialysis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patient will undergo dialysis at 35 degrees Celsius to assess if this affects the liver function and perfusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Cooler dialysis</intervention_name>
    <description>Having dialysis at a slightly cooler temperature (35 vs 36.5 degrees Celsius)</description>
    <arm_group_label>Cooler Dialysis</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard Dialysis</intervention_name>
    <description>Having dialysis at a standard temperature (36.5 degrees Celsius)</description>
    <arm_group_label>Standard Dialysis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be able to provide informed consent&#xD;
&#xD;
          -  Age greater than 18 years&#xD;
&#xD;
          -  Hemodialysis for at least 3 months&#xD;
&#xD;
          -  No significant residual renal function (&lt;250mls urine/day)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Chronic liver disease of any stage&#xD;
&#xD;
          -  Chronic intestinal disease excluding Irritable Bowel Syndrome (IBS)&#xD;
&#xD;
          -  Previous liver transplant or liver resection&#xD;
&#xD;
          -  Previous Transjugular Portosystemic Shunt (TIPSS) insertion&#xD;
&#xD;
          -  Active infection or malignancy&#xD;
&#xD;
          -  Pregnant, breastfeeding or intending pregnancy&#xD;
&#xD;
          -  Unable to give consent or understand written information&#xD;
&#xD;
          -  Diabetic and experiencing hypoglycemia during dialysis within the last 2 months&#xD;
&#xD;
          -  Known allergy/intolerance to contrast agent or iodides&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chris W McIntyre, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Western University, Canada</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <last_update_submitted>August 16, 2018</last_update_submitted>
  <last_update_submitted_qc>August 16, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Lawson Health Research Institute</investigator_affiliation>
    <investigator_full_name>Chris McIntyre</investigator_full_name>
    <investigator_title>Professor of Medicine, UWO</investigator_title>
  </responsible_party>
  <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/NCT02997774
org study id: 108616
nct id: NCT02997774
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Having hemodialysis affects the blood supply to various organs in the body including the
      heart and the brain. With time, these effects build up and can affect the way these organs
      function. The investigators have previously shown that the liver (a key organ which works to
      help clean the blood, make proteins and turn all your food into energy) is also affected. One
      of the ways to help protect organs from injury due to dialysis has been cooling during
      dialysis. The investigators want to examine whether cooling during dialysis protects the
      blood supply to the liver. CT imaging will be used to measure this blood supply during
      hemodialysis with standard and cooler settings.
Hemodialysis exerts significant hemodynamic effects with widespread consequences on
      vulnerable vascular beds. Cardiac injury, including myocardial stunning and subclinical
      myocardial ischemia, appears to be common and associated with significantly increased
      mortality. The liver has been shown to have preserved blood flow due to its dual blood
      supply. Even so, the liver excretory function is decreased and endotoxin levels in the blood
      increase during hemodialysis. Extracorporeal cooling during dialysis has been associated with
      protective effects on the brain and heart of dialysis patients. The effects of cooler
      dialysis on liver perfusion, function and endotoxemia during hemodialysis is unknown.

      The investigators therefore propose to use CT perfusion imaging to examine the effect of
      cooling during hemodialysis on liver perfusion, relating this effect to endotoxin
      translocation and myocardial dysfunction. Additionally, they intend to investigate the
      potential effects on hepatic function in this context, examining the relationship between
      liver perfusion and endotoxemia, the metabolism of uremic toxins and clinical symptoms of
      uremia.

      This is a prospective randomized cross-over study involving a single center recruiting
      patients from the prevalent dialysis population of London Health Sciences Centre (LHSC) Renal
      Program. Once recruited, patients will undergo two study hemodialysis sessions - one will use
      standard dialysate temperature of 36.5 degrees Celsius (HD36.5) and one will use cooler
      dialysate temperature at 35 degrees Celsius (HD35). The order of these two sessions will be
      randomly allocated. Before, during and after each session, participants will undergo cardiac
      and hepatic assessment. This will include CT scans, 2D echocardiography and indocyanine green
      (ICG) clearance measurements. In addition, participants will answer a number of
      questionnaires about uremic symptoms and blood tests will also be done.

      The investigators' aim is to characterize and compare liver function and perfusion before
      during and after hemodialysis, with standard and cooler dialysate temperature.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Single (Outcomes Assessor)
masking description: Neither subjects nor the investigator at the study visits will be blinded; however, analysis of imaging data will be performed with the operator blinded to allocation.
measure: Change in regional liver perfusion in mls/min/100g from baseline to peak stress during dialysis (3 hours into the dialysis session) with standard versus cooler dialysate temperature.
time frame: 2 years
measure: Change in global liver perfusion in mls/min/100g pre, during and post-dialysis with cooler dialysate
time frame: 2 years
measure: ICG clearance rate pre, during and post-dialysis with cooler vs standard dialysate
time frame: 2 years
measure: Contribution of portal venous flow to hepatic perfusion (PV fraction) pre, during and post-dialysis with cooler vs standard dialysate
time frame: 2 years
measure: Endotoxin levels with cooler vs standard dialysate
time frame: 2 years
measure: Troponin T levels with cooler vs standard dialysate
time frame: 2 years
measure: Number of stunned myocardial segments with cooler vs standard dialysate
time frame: 2 years
measure: Uremic toxin levels with cooler vs standard dialysate
time frame: 2 years
measure: Uremic symptom scores with cooler vs standard dialysate
time frame: 2 years
arm group label: Standard Dialysis
arm group type: Active Comparator
description: Patient will undergo dialysis at 36.5 degrees Celsius to assess if this affects the liver function and perfusion
arm group label: Cooler Dialysis
arm group type: Experimental
description: Patient will undergo dialysis at 35 degrees Celsius to assess if this affects the liver function and perfusion
intervention type: Other
intervention name: Cooler dialysis
description: Having dialysis at a slightly cooler temperature (35 vs 36.5 degrees Celsius)
arm group label: Cooler Dialysis
intervention type: Other
intervention name: Standard Dialysis
description: Having dialysis at a standard temperature (36.5 degrees Celsius)
arm group label: Standard Dialysis
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chris W McIntyre, PhD
role: Principal Investigator
affiliation: Western University, Canada
facility: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: Lawson Health Research Institute
investigator full name: Chris McIntyre
investigator title: Professor of Medicine, UWO
sharing ipd: No