<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/NCT03004547</url>
  </required_header>
  <id_info>
    <org_study_id>108765</org_study_id>
    <nct_id>NCT03004547</nct_id>
  </id_info>
  <brief_title>Sodium Deposition in Soft Tissues of Patients With Kidney Disease</brief_title>
  <official_title>Evaluation of Sodium Deposition in Soft Tissues of Patients With Kidney Disease and Its Association With Patient Symptomatology</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Sodium (Na+) hemostasis is abnormal in CKD patients, and this element can be deposited in the&#xD;
      skin, muscle, and skeleton - to cope with long term sodium loading. It is known that sodium&#xD;
      stored in this non-osmotically active way, is profoundly inflammatory. Furthermore,&#xD;
      inflammation has been associated with several uremic symptoms. The investigators will use&#xD;
      novel Na+ MRI imaging to examine the Na+ deposition in the skin, muscle, and skeleton of five&#xD;
      groups:1) chronic in-center hemodialysis patients, 2) chronic peritoneal dialysis patients,&#xD;
      3) adult and paediatric patients with CKD stage 1-5 and 4) heart failure patients with and&#xD;
      without renal dysfunction 5) sex and age-matched healthy adult and paediatric controls.&#xD;
      Additionally, they will investigate the association between sodium deposition in these&#xD;
      tissues with uremic symptomatology and biochemical markers of metabolism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Kidneys have a key role in sodium hemostasis through their excretory function. In patients&#xD;
      with chronic kidney disease (CKD), kidney function is impaired; thus, suggesting that sodium&#xD;
      handling is abnormal in this setting with long-term sodium loading (from oral intake) and&#xD;
      lack of adequate urinary excretion. Yet, sodium concentration needs to stay relatively&#xD;
      constant to prevent fatal intra-cellular accumulation, which would result in cell injury and&#xD;
      death. In hemodialysis patients, at least a part of this extra sodium is non-osmotically&#xD;
      active and deposited in the skin, muscle, and skeleton.&#xD;
&#xD;
      Furthermore, it has become increasingly recognized that sodium (once accumulated in tissues)&#xD;
      is directly pro-inflammatory, affecting the innate immune system by regulating the activity&#xD;
      of macrophages in skin. This linkage between sodium and inflammation indicates a potential&#xD;
      link between sodium deposition and uremic symptoms experienced by patients.&#xD;
&#xD;
      There have been no studies to date examining the sodium deposition in the skin, muscle, and&#xD;
      skeleton of patients with different kidney function and renal replacement therapy.&#xD;
&#xD;
      This is a pilot study involving a single center recruiting patients from the prevalent&#xD;
      maintenance hemodialysis, peritoneal dialysis , CKD stage 1-5, and heart failure populations&#xD;
      of London, Ontario, compared to healthy controls. Once recruited, participants will undergo&#xD;
      one study visit with the potential of up to two follow-up visits (on a non-dialysis day for&#xD;
      hemodialysis patients). Participants will be followed for up to two years after the first&#xD;
      study visit. Each session will include symptom questionnaires, the five times sit to stand&#xD;
      and 60-second chair stand test (excluding all children), blood pressure and heart rate&#xD;
      measurements, blood work (excluding healthy children and adolescents), urine sampling&#xD;
      (excluding those on dialysis), an echocardiogram (excluding healthy controls), and an MRI&#xD;
      scan of the lower leg detecting sodium content.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 5, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2023</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>Na content in the skin, muscle and skeleton of five cohorts</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Marker: CRP levels</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Uremic symptom scores among the different groups</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver function markers</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Liver damage markers (liver enzymes)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>cardiac markers (troponin)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>bone markers (ALP, vitamin D levels)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Uremic toxin levels</measure>
    <time_frame>3-4 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Endotoxin levels</measure>
    <time_frame>5 years</time_frame>
  </secondary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Haemodialysis Complication</condition>
  <arm_group>
    <arm_group_label>Chronic hemodialysis patients</arm_group_label>
    <description>Patients on standard in-centre 3 times a week hemodialysis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Peritoneal dialysis patients</arm_group_label>
    <description>Patients on peritoneal dialysis</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Adult and paediatric patients with CKD stage 1-5</arm_group_label>
    <description>Patients with chronic kidney disease stage 1-5 (not dialysis dependent)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy adult and paediatric controls</arm_group_label>
    <description>Subjects without kidney disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Heart failure patients with and without renal dysfunction</arm_group_label>
    <description>Heart failure patients (atrial fibrillation etc ...) with and without renal dysfunction</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Measuring sodium content</intervention_name>
    <description>Sodium MRI measurement of sodium content in the tissues of all participants</description>
    <arm_group_label>Adult and paediatric patients with CKD stage 1-5</arm_group_label>
    <arm_group_label>Chronic hemodialysis patients</arm_group_label>
    <arm_group_label>Healthy adult and paediatric controls</arm_group_label>
    <arm_group_label>Heart failure patients with and without renal dysfunction</arm_group_label>
    <arm_group_label>Peritoneal dialysis patients</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      We will measure complete blood count, urea and electrolytes, magnesium, calcium, phosphate,&#xD;
      liver function tests, clotting markers, cardiac biomarkers (Troponin T), 25-hydroxyVitamin D&#xD;
      and 1,25-dihydroxyVitamin D, CRP, glucose, intact PTH, creatinine, cystatin C, and lactate.&#xD;
&#xD;
      A portion of this blood sample will be sent to the laboratory on-site and the remaining&#xD;
      portion will be for processed on-site and stored in the Kidney Clinical Research Unit, LHSC&#xD;
      until the end of the study when endotoxin and uremic toxin measurement will be performed.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        We will recruit up to 400 participants; approximately 125 dialysis patients including 50&#xD;
        children/adolescents on dialysis, 200 patients with various stages of chronic kidney&#xD;
        disease including heart failure patients and approximately 25 children/adolescents with&#xD;
        chronic kidney disease, and 75 individuals with no kidney disease including approximately&#xD;
        25 healthy children/adolescents.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age greater than or equal to 6 years&#xD;
&#xD;
          -  For patients on maintenance hemodialysis or peritoneal dialysis: more than 3 months&#xD;
             duration of therapy&#xD;
&#xD;
          -  For patients with CKD stage 1-5: CKD stage 1-5 and no indications to start dialysis&#xD;
&#xD;
          -  For heart failure patients: with or without renal dysfunction&#xD;
&#xD;
          -  For healthy controls: lack of kidney disease, heart failure, liver cirrhosis, and&#xD;
             peripheral edema&#xD;
&#xD;
        For subsequent visits (must meet 1 of the below indicators):&#xD;
&#xD;
          -  Change in dialysis prescription&#xD;
&#xD;
          -  Change in renal replacement therapy modality&#xD;
&#xD;
          -  Change in medication&#xD;
&#xD;
          -  Parathyroidectomy&#xD;
&#xD;
          -  Intervention added to or removed from dialysis (i.e. such as but not limited exercise,&#xD;
             cooling, and ischemic preconditioning)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant, breastfeeding or intending pregnancy&#xD;
&#xD;
          -  Unable to give consent or understand written information&#xD;
&#xD;
          -  Contraindication to MRI study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Christopher W McIntyre, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Western University, Canada</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Christopher W McIntyre, PhD, MD</last_name>
    <phone>519-685-8500</phone>
    <phone_ext>58502</phone_ext>
    <email>christopher.mcintyre@lhsc.on.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alireza Akbari, PhD</last_name>
    <email>aakbari@uwo.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>LHSC Regional Renal Care Program</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher W McIntyre, MD, PhD</last_name>
      <phone>519-685-8500</phone>
      <phone_ext>58502</phone_ext>
      <email>christopher.mcintyre@lhsc.on.cas</email>
    </contact>
    <investigator>
      <last_name>Alireza Akbari, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Guido Filler, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Jean Theberge, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Timothy Scholl, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>December 21, 2022</last_update_submitted>
  <last_update_submitted_qc>December 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2022</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>
  <keyword>Sodium</keyword>
  <keyword>Soft Tissues</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</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/NCT03004547
org study id: 108765
nct id: NCT03004547
lead sponsor: 
has dmc: No
Sodium (Na+) hemostasis is abnormal in CKD patients, and this element can be deposited in the
      skin, muscle, and skeleton - to cope with long term sodium loading. It is known that sodium
      stored in this non-osmotically active way, is profoundly inflammatory. Furthermore,
      inflammation has been associated with several uremic symptoms. The investigators will use
      novel Na+ MRI imaging to examine the Na+ deposition in the skin, muscle, and skeleton of five
      groups:1) chronic in-center hemodialysis patients, 2) chronic peritoneal dialysis patients,
      3) adult and paediatric patients with CKD stage 1-5 and 4) heart failure patients with and
      without renal dysfunction 5) sex and age-matched healthy adult and paediatric controls.
      Additionally, they will investigate the association between sodium deposition in these
      tissues with uremic symptomatology and biochemical markers of metabolism.
Kidneys have a key role in sodium hemostasis through their excretory function. In patients
      with chronic kidney disease (CKD), kidney function is impaired; thus, suggesting that sodium
      handling is abnormal in this setting with long-term sodium loading (from oral intake) and
      lack of adequate urinary excretion. Yet, sodium concentration needs to stay relatively
      constant to prevent fatal intra-cellular accumulation, which would result in cell injury and
      death. In hemodialysis patients, at least a part of this extra sodium is non-osmotically
      active and deposited in the skin, muscle, and skeleton.

      Furthermore, it has become increasingly recognized that sodium (once accumulated in tissues)
      is directly pro-inflammatory, affecting the innate immune system by regulating the activity
      of macrophages in skin. This linkage between sodium and inflammation indicates a potential
      link between sodium deposition and uremic symptoms experienced by patients.

      There have been no studies to date examining the sodium deposition in the skin, muscle, and
      skeleton of patients with different kidney function and renal replacement therapy.

      This is a pilot study involving a single center recruiting patients from the prevalent
      maintenance hemodialysis, peritoneal dialysis , CKD stage 1-5, and heart failure populations
      of London, Ontario, compared to healthy controls. Once recruited, participants will undergo
      one study visit with the potential of up to two follow-up visits (on a non-dialysis day for
      hemodialysis patients). Participants will be followed for up to two years after the first
      study visit. Each session will include symptom questionnaires, the five times sit to stand
      and 60-second chair stand test (excluding all children), blood pressure and heart rate
      measurements, blood work (excluding healthy children and adolescents), urine sampling
      (excluding those on dialysis), an echocardiogram (excluding healthy controls), and an MRI
      scan of the lower leg detecting sodium content.
observational model: Cohort
time perspective: Prospective
measure: Na content in the skin, muscle and skeleton of five cohorts
time frame: 2 years
measure: Inflammatory Marker: CRP levels
time frame: 2 years
measure: Uremic symptom scores among the different groups
time frame: 2 years
measure: Liver function markers
time frame: 2 years
measure: Liver damage markers (liver enzymes)
time frame: 2 years
measure: cardiac markers (troponin)
time frame: 2 years
measure: bone markers (ALP, vitamin D levels)
time frame: 2 years
measure: Uremic toxin levels
time frame: 3-4 years
measure: Endotoxin levels
time frame: 5 years
arm group label: Chronic hemodialysis patients
description: Patients on standard in-centre 3 times a week hemodialysis
arm group label: Peritoneal dialysis patients
description: Patients on peritoneal dialysis
arm group label: Adult and paediatric patients with CKD stage 1-5
description: Patients with chronic kidney disease stage 1-5 (not dialysis dependent)
arm group label: Healthy adult and paediatric controls
description: Subjects without kidney disease
arm group label: Heart failure patients with and without renal dysfunction
description: Heart failure patients (atrial fibrillation etc ...) with and without renal dysfunction
intervention type: Other
intervention name: Measuring sodium content
description: Sodium MRI measurement of sodium content in the tissues of all participants
arm group label: Adult and paediatric patients with CKD stage 1-5
arm group label: Chronic hemodialysis patients
arm group label: Healthy adult and paediatric controls
arm group label: Heart failure patients with and without renal dysfunction
arm group label: Peritoneal dialysis patients
We will measure complete blood count, urea and electrolytes, magnesium, calcium, phosphate,
      liver function tests, clotting markers, cardiac biomarkers (Troponin T), 25-hydroxyVitamin D
      and 1,25-dihydroxyVitamin D, CRP, glucose, intact PTH, creatinine, cystatin C, and lactate.

      A portion of this blood sample will be sent to the laboratory on-site and the remaining
      portion will be for processed on-site and stored in the Kidney Clinical Research Unit, LHSC
      until the end of the study when endotoxin and uremic toxin measurement will be performed.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Christopher W McIntyre, PhD, MD
role: Principal Investigator
affiliation: Western University, Canada
last name: Christopher W McIntyre, PhD, MD
phone: 519-685-8500
phone ext: 58502
email: christopher.mcintyre@lhsc.on.ca
last name: Alireza Akbari, PhD
email: aakbari@uwo.ca
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Canada
responsible party type: Sponsor-Investigator
investigator affiliation: Lawson Health Research Institute
investigator full name: Chris McIntyre
investigator title: Professor of Medicine, UWO
mesh term: Kidney Diseases
sharing ipd: No