<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/NCT01691196</url>
  </required_header>
  <id_info>
    <org_study_id>2012-0506</org_study_id>
    <secondary_id>Baxter/UIC Ref#2012-04881</secondary_id>
    <nct_id>NCT01691196</nct_id>
  </id_info>
  <brief_title>Inflammation in Peritoneal Dialysis Patients: Effect of Obesity</brief_title>
  <official_title>Inflammation in Peritoneal Dialysis Patients: Effect of Obesity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Illinois at Chicago</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Illinois at Chicago</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Our study addresses the following research question: What is the role of obesity in&#xD;
      modulating inflammation and innate immune function, as well as the overall responsiveness of&#xD;
      innate immune cells (such as macrophages, neutrophils, and other peripheral leukocytes) in&#xD;
      patients undergoing peritoneal dialysis?&#xD;
&#xD;
      The investigators hypothesize that obesity will lead to increased inflammation in patients&#xD;
      undergoing peritoneal dialysis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic inflammation is highly prevalent in ESRD and associated with adverse outcomes. For&#xD;
      example, chronic exposure of the peritoneal cavity to PD solution leads to induction of&#xD;
      cytokines and other inflammatory mediators, generating peritoneal membrane inflammation which&#xD;
      results in functional decline of ultrafiltration. Obesity is characterized by a state of&#xD;
      chronic low-grade systemic inflammation stemming from expanded adipose tissue mass. Animal&#xD;
      studies from our group and others suggest that obesity is associated with exacerbated&#xD;
      prolonged inflammatory responses in the peritoneal cavity. The shifting demographic&#xD;
      characteristics of the ESRD population, with a rise in elderly patients and those with&#xD;
      obesity, is as a significant challenge for management of dialysis patients. Specifically, a&#xD;
      2-fold increase in the percentage of obese patients in the ESRD population has been reported.&#xD;
      The caloric burden of PD glucose-containing solutions adds an additional risk for development&#xD;
      or exacerbation of obesity and diabetes in patients using this dialysis modality. Few studies&#xD;
      have directly evaluated the association between degree of adiposity and inflammation in PD&#xD;
      patients. Data obtained from the proposed experiments will help clarify the connection&#xD;
      between obesity and risk factors for cardiovascular and infectious diseases in the PD&#xD;
      population. These data will also further our knowledge of the basic pathophysiology of both&#xD;
      obesity and ESRD and enhance our understanding of factors involved in successful delivery of&#xD;
      PD. Results may lead to enhanced nutritional recommendations for PD patients and/or the use&#xD;
      of low-glucose or non-glucose alternatives, with a resultant reduction in local and/or&#xD;
      systemic inflammation and CVD and other risk factors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study not initiated&#xD;
  </why_stopped>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">September 2017</completion_date>
  <primary_completion_date type="Actual">September 2017</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>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma and dialysate levels of pro-inflammatory and anti-inflammatory molecules</measure>
    <time_frame>24 hours</time_frame>
    <description>Peritoneal dialysate effluent (PDE) and peripheral blood will be obtained from peritoneal dialysis (PD) subjects. Levels of pro- and anti-inflammatory cytokines, chemokines, adipokines, and acute-phase reactants will be evaluated in PDE and plasma. The ability of peripheral leukocytes to respond to microbial stimuli will be studied using whole blood cultures. We predict percentage of body fat will be significantly associated with higher levels of pro-inflammatory factors both systemically and locally and with reduced ability of peripheral leukocytes to respond to microbial stimuli.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peritoneal macrophage subphenotype</measure>
    <time_frame>24 hours</time_frame>
    <description>The composition of leukocytes from peritoneal dialysate effluent (PDE) will be analyzed to evaluate the absolute and relative amounts of leukocyte subclasses. The phenotype of peritoneal macrophages (pMac) will be evaluated by flow cytometry, by real time RT-PCR, and by measurement of mediators characteristic of each activation type following ex vivo culture. We predict that we will observe a significant shift from an anti- to a pro-inflammatory pMac phenotype as adiposity increases</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Measurement of adiposity/obesity</measure>
    <time_frame>24 hours</time_frame>
    <description>DXA (dual energy X-ray absorptiometry) will be conducted at UIC body composition laboratory using Hologic 4500 W Elite Scan. Values from DXA scans will be primary method for evaluation of adiposity. Height and weight will be measured by nurse to calculate body mass index (BMI).</description>
  </other_outcome>
  <enrollment type="Actual">0</enrollment>
  <condition>End-Stage Renal Disease</condition>
  <condition>Renal Disease, End-Stage</condition>
  <condition>Renal Failure, End-Stage</condition>
  <condition>Obesity</condition>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood Collection: Venous blood after overnight fast will include: (1) heparinized tube (green&#xD;
      top) for whole blood (WB) cultures; (2) EDTA tube (lavender top) for CBC and measurement of&#xD;
      cytokines and adipokines, and (3) serum-separator (red top) for determination of lipid panel,&#xD;
      glucose, insulin, and hemoglobin A1c. Glucose and insulin will be used to calculate HOMA-IR&#xD;
      (index of insulin resistance).&#xD;
&#xD;
      Collection of peritoneal dialysis effluent (PDE): To minimize variability, 2.5% glucose&#xD;
      peritoneal dialysis (PD) solution and 4h dwell time will be used for all patients on test&#xD;
      day. Immediately after collection, PDE will be chilled before further processing.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients undergoing peritoneal dialysis&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. &gt; 18 years; and&#xD;
&#xD;
          2. peritoneal dialysis (PD) &gt; 6 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. infectious episode within 4 weeks; and&#xD;
&#xD;
          2. using immunosuppressive drugs&#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>Jerrold S Levine, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UIC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Natalia Litbarg, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UIC</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Giamila Fantuzzi, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>UIC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Illinois at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 24, 2012</study_first_posted>
  <last_update_submitted>October 28, 2019</last_update_submitted>
  <last_update_submitted_qc>October 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Illinois at Chicago</investigator_affiliation>
    <investigator_full_name>Jerrold S. Levine</investigator_full_name>
    <investigator_title>Associate Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>Obesity</keyword>
  <keyword>Peritoneal dialysis</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Macrophages</keyword>
  <keyword>Innate immunity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Kidney Failure, Chronic</mesh_term>
    <mesh_term>Obesity</mesh_term>
    <mesh_term>Inflammation</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/NCT01691196
org study id: 2012-0506
secondary id: Baxter/UIC Ref#2012-04881
nct id: NCT01691196
lead sponsor: 
has dmc: Yes
Our study addresses the following research question: What is the role of obesity in
      modulating inflammation and innate immune function, as well as the overall responsiveness of
      innate immune cells (such as macrophages, neutrophils, and other peripheral leukocytes) in
      patients undergoing peritoneal dialysis?

      The investigators hypothesize that obesity will lead to increased inflammation in patients
      undergoing peritoneal dialysis.
Chronic inflammation is highly prevalent in ESRD and associated with adverse outcomes. For
      example, chronic exposure of the peritoneal cavity to PD solution leads to induction of
      cytokines and other inflammatory mediators, generating peritoneal membrane inflammation which
      results in functional decline of ultrafiltration. Obesity is characterized by a state of
      chronic low-grade systemic inflammation stemming from expanded adipose tissue mass. Animal
      studies from our group and others suggest that obesity is associated with exacerbated
      prolonged inflammatory responses in the peritoneal cavity. The shifting demographic
      characteristics of the ESRD population, with a rise in elderly patients and those with
      obesity, is as a significant challenge for management of dialysis patients. Specifically, a
      2-fold increase in the percentage of obese patients in the ESRD population has been reported.
      The caloric burden of PD glucose-containing solutions adds an additional risk for development
      or exacerbation of obesity and diabetes in patients using this dialysis modality. Few studies
      have directly evaluated the association between degree of adiposity and inflammation in PD
      patients. Data obtained from the proposed experiments will help clarify the connection
      between obesity and risk factors for cardiovascular and infectious diseases in the PD
      population. These data will also further our knowledge of the basic pathophysiology of both
      obesity and ESRD and enhance our understanding of factors involved in successful delivery of
      PD. Results may lead to enhanced nutritional recommendations for PD patients and/or the use
      of low-glucose or non-glucose alternatives, with a resultant reduction in local and/or
      systemic inflammation and CVD and other risk factors.
observational model: Cohort
time perspective: Cross-Sectional
measure: Plasma and dialysate levels of pro-inflammatory and anti-inflammatory molecules
time frame: 24 hours
description: Peritoneal dialysate effluent (PDE) and peripheral blood will be obtained from peritoneal dialysis (PD) subjects. Levels of pro- and anti-inflammatory cytokines, chemokines, adipokines, and acute-phase reactants will be evaluated in PDE and plasma. The ability of peripheral leukocytes to respond to microbial stimuli will be studied using whole blood cultures. We predict percentage of body fat will be significantly associated with higher levels of pro-inflammatory factors both systemically and locally and with reduced ability of peripheral leukocytes to respond to microbial stimuli.
measure: Peritoneal macrophage subphenotype
time frame: 24 hours
description: The composition of leukocytes from peritoneal dialysate effluent (PDE) will be analyzed to evaluate the absolute and relative amounts of leukocyte subclasses. The phenotype of peritoneal macrophages (pMac) will be evaluated by flow cytometry, by real time RT-PCR, and by measurement of mediators characteristic of each activation type following ex vivo culture. We predict that we will observe a significant shift from an anti- to a pro-inflammatory pMac phenotype as adiposity increases
measure: Measurement of adiposity/obesity
time frame: 24 hours
description: DXA (dual energy X-ray absorptiometry) will be conducted at UIC body composition laboratory using Hologic 4500 W Elite Scan. Values from DXA scans will be primary method for evaluation of adiposity. Height and weight will be measured by nurse to calculate body mass index (BMI).
Blood Collection: Venous blood after overnight fast will include: (1) heparinized tube (green
      top) for whole blood (WB) cultures; (2) EDTA tube (lavender top) for CBC and measurement of
      cytokines and adipokines, and (3) serum-separator (red top) for determination of lipid panel,
      glucose, insulin, and hemoglobin A1c. Glucose and insulin will be used to calculate HOMA-IR
      (index of insulin resistance).

      Collection of peritoneal dialysis effluent (PDE): To minimize variability, 2.5% glucose
      peritoneal dialysis (PD) solution and 4h dwell time will be used for all patients on test
      day. Immediately after collection, PDE will be chilled before further processing.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jerrold S Levine, MD
role: Principal Investigator
affiliation: UIC
last name: Natalia Litbarg, MD
role: Principal Investigator
affiliation: UIC
last name: Giamila Fantuzzi, PhD
role: Principal Investigator
affiliation: UIC
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Illinois at Chicago
investigator full name: Jerrold S. Levine
investigator title: Associate Professor of Medicine
mesh term: Kidney Diseases
mesh term: Kidney Failure, Chronic
mesh term: Obesity
mesh term: Inflammation