<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/NCT02231203</url>
  </required_header>
  <id_info>
    <org_study_id>NL46230.029.13</org_study_id>
    <nct_id>NCT02231203</nct_id>
  </id_info>
  <brief_title>Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function</brief_title>
  <acronym>EMPIRE</acronym>
  <official_title>Effect of Intravenous Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function in Patients With Colon Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical Center Alkmaar</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical Center Alkmaar</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Ideally, the postoperative inflammatory response is part of a well-orchestrated mechanism&#xD;
      that contributes to tissue healing and rapid recovery. An exaggerated uncontrolled&#xD;
      inflammatory response, however may lead to catabolism, tissue damage and organ failure.&#xD;
      Omega-3 fatty acids may provide a means to alter cellular immune responses to the benefit of&#xD;
      the patient. When omega-3 fatty acids are incorporated into membranes of inflammatory cells,&#xD;
      they trigger intracellular signalling pathways that result in a less pro-inflammatory&#xD;
      response. They modify gene and protein expression, modulate membrane protein activity and act&#xD;
      as a reservoir for bioactive molecules. They also have a strong anti-inflammatory effect by&#xD;
      mediating resolution of the inflammation. Furthermore, omega-3 fatty acids improve&#xD;
      erythrocyte function, which is vital for an adequate microcirculation, tissue oxygenation and&#xD;
      wound healing.&#xD;
&#xD;
      The investigators hypothesize that the perioperative administration of intravenous omega-3&#xD;
      fatty acids results in a rapid incorporation in immune cells and erythrocytes, thereby&#xD;
      reducing the postoperative inflammatory response and improving erythrocyte function in&#xD;
      patients undergoing colorectal surgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ex vivo production of pro-inflammatory cytokine IL-6 in LPS stimulated whole blood</measure>
    <time_frame>baseline, day of surgery, postoperative day 1,2 and 4</time_frame>
    <description>Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine IL-6, measured in ng/ml.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in ex vivo production of TNF-α and IL-10 in LPS stimulated whole blood</measure>
    <time_frame>baseline, day of surgery, postoperative day 1, 2 and 4</time_frame>
    <description>Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine TNF-α (tumor necrosis factor-α), and the anti-inflammatory cytokine IL-10 (interleukine-10), both measured in ng/ml.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in erythrocyte function</measure>
    <time_frame>baseline, day of surgery, postoperative day 1, 2 and 4</time_frame>
    <description>Erythrocyte deformability and aggregation measured by LORRCA (laser assisted optical rotational red cell analyzer)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in in vivo systemic inflammatory response parameters</measure>
    <time_frame>baseline, day of surgery, postoperative day 1, 2 and 4</time_frame>
    <description>White blood cell count, C-reactive protein and cytokine levels (Interleukine-6, Tumor Necrosis Factor-α and Interleukine-10) in serum.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Postoperative outcome (composite measure of length of stay and complications)</measure>
    <time_frame>Registration during admission, follow up 2 and 4 weeks after surgery</time_frame>
    <description>Length of hospital stay and occurence of surgical site infection, abscess, urinary tract infection, pneumonia, anastomotic leakage, need for Intensive Care Unit admission, Systemic Inflammatory Response Syndrome, Multi Organ Failure, any adverse events.</description>
  </other_outcome>
  <other_outcome>
    <measure>Cognitive function</measure>
    <time_frame>baseline, follow up 2 weeks after surgery</time_frame>
    <description>Neuropsychological examination using a reading test, an auditory verbal learning test, WAIS III figure series and trail making tests.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Colon Cancer</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>2 infusions of NaCl, 2 ml/kg, one the night before operation and one the day after operation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Omegaven</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 infusions of 2ml/kg, one the night before surgery and one the day after surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omegaven</intervention_name>
    <description>2 infusions, 2 ml/kg, one the night before operation and one the day after operation</description>
    <arm_group_label>Omegaven</arm_group_label>
    <other_name>purified fish oil</other_name>
    <other_name>omega-3 fatty acids</other_name>
    <other_name>eicosapentaenoicacid (EPA)</other_name>
    <other_name>docosahexaenoicacid (DHA)</other_name>
    <other_name>dl-a- tocopherol (antioxidant)</other_name>
    <other_name>Omegaven-Fresenius</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2 infusions, 2 ml/kg, one the night before operation and one the day after operation</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>NaCl 0,9%</other_name>
    <other_name>Natriumchloride 0,9%</other_name>
    <other_name>glass container NaCl 0,9% Fresenius Kabi</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients (male or female) undergoing elective laparoscopic surgery for colon cancer&#xD;
&#xD;
          -  Age between 60 and 80 years&#xD;
&#xD;
          -  BMI between 20 kg/m2 and below 30 kg/m2&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participation in or having participated in another clinical trial within the previous&#xD;
             3 months&#xD;
&#xD;
          -  Indications for continuously use of anticoagulant medication and no possibility to&#xD;
             stop these medication perioperatively, for example patients with an artificial heart&#xD;
             valve&#xD;
&#xD;
          -  Pre-operative Hemoglobin&lt;5.0 mmol/L&#xD;
&#xD;
          -  Metastatic disease&#xD;
&#xD;
          -  Very poor peripheral venous access&#xD;
&#xD;
          -  Current history of inflammatory or infectious disease&#xD;
&#xD;
          -  The use of anti-inflammatory drugs&#xD;
&#xD;
          -  The use of thyroid medication&#xD;
&#xD;
          -  The use of fish oil products or fish consumption more than 2 times a week&#xD;
&#xD;
          -  Contra-indication for the use of Omegaven-Fresenius, including:&#xD;
&#xD;
          -  General contra-indications for parenteral nutrition&#xD;
&#xD;
          -  Allergy to fish or egg protein.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>A.P.J. Houdijk, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical Center of Alkmaar</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical Center of Alkmaar</name>
      <address>
        <city>Alkmaar</city>
        <state>Noord Holland</state>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>July 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <last_update_submitted>July 28, 2018</last_update_submitted>
  <last_update_submitted_qc>July 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical Center Alkmaar</investigator_affiliation>
    <investigator_full_name>Alexander P.J. Houdijk</investigator_full_name>
    <investigator_title>Dr.</investigator_title>
  </responsible_party>
  <keyword>fish oil</keyword>
  <keyword>omega-3 fatty acids</keyword>
  <keyword>postoperative inflammatory response</keyword>
  <keyword>erythrocyte function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colonic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tocopherols</mesh_term>
    <mesh_term>Antioxidants</mesh_term>
  </intervention_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/NCT02231203
org study id: NL46230.029.13
nct id: NCT02231203
lead sponsor: 
has dmc: Yes
Ideally, the postoperative inflammatory response is part of a well-orchestrated mechanism
      that contributes to tissue healing and rapid recovery. An exaggerated uncontrolled
      inflammatory response, however may lead to catabolism, tissue damage and organ failure.
      Omega-3 fatty acids may provide a means to alter cellular immune responses to the benefit of
      the patient. When omega-3 fatty acids are incorporated into membranes of inflammatory cells,
      they trigger intracellular signalling pathways that result in a less pro-inflammatory
      response. They modify gene and protein expression, modulate membrane protein activity and act
      as a reservoir for bioactive molecules. They also have a strong anti-inflammatory effect by
      mediating resolution of the inflammation. Furthermore, omega-3 fatty acids improve
      erythrocyte function, which is vital for an adequate microcirculation, tissue oxygenation and
      wound healing.

      The investigators hypothesize that the perioperative administration of intravenous omega-3
      fatty acids results in a rapid incorporation in immune cells and erythrocytes, thereby
      reducing the postoperative inflammatory response and improving erythrocyte function in
      patients undergoing colorectal surgery.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in ex vivo production of pro-inflammatory cytokine IL-6 in LPS stimulated whole blood
time frame: baseline, day of surgery, postoperative day 1,2 and 4
description: Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine IL-6, measured in ng/ml.
measure: Change in ex vivo production of TNF-α and IL-10 in LPS stimulated whole blood
time frame: baseline, day of surgery, postoperative day 1, 2 and 4
description: Ex vivo stimulation of whole blood with LPS (lipopolysaccharide, component of gram negative bacteria) resulting in the production of the pro-inflammatory cytokine TNF-α (tumor necrosis factor-α), and the anti-inflammatory cytokine IL-10 (interleukine-10), both measured in ng/ml.
measure: Change in erythrocyte function
time frame: baseline, day of surgery, postoperative day 1, 2 and 4
description: Erythrocyte deformability and aggregation measured by LORRCA (laser assisted optical rotational red cell analyzer)
measure: Change in in vivo systemic inflammatory response parameters
time frame: baseline, day of surgery, postoperative day 1, 2 and 4
description: White blood cell count, C-reactive protein and cytokine levels (Interleukine-6, Tumor Necrosis Factor-α and Interleukine-10) in serum.
measure: Postoperative outcome (composite measure of length of stay and complications)
time frame: Registration during admission, follow up 2 and 4 weeks after surgery
description: Length of hospital stay and occurence of surgical site infection, abscess, urinary tract infection, pneumonia, anastomotic leakage, need for Intensive Care Unit admission, Systemic Inflammatory Response Syndrome, Multi Organ Failure, any adverse events.
measure: Cognitive function
time frame: baseline, follow up 2 weeks after surgery
description: Neuropsychological examination using a reading test, an auditory verbal learning test, WAIS III figure series and trail making tests.
arm group label: Placebo
arm group type: Placebo Comparator
description: 2 infusions of NaCl, 2 ml/kg, one the night before operation and one the day after operation.
arm group label: Omegaven
arm group type: Active Comparator
description: 2 infusions of 2ml/kg, one the night before surgery and one the day after surgery
intervention type: Drug
intervention name: Omegaven
description: 2 infusions, 2 ml/kg, one the night before operation and one the day after operation
arm group label: Omegaven
other name: purified fish oil
other name: omega-3 fatty acids
other name: eicosapentaenoicacid (EPA)
other name: docosahexaenoicacid (DHA)
other name: dl-a- tocopherol (antioxidant)
other name: Omegaven-Fresenius
intervention type: Drug
intervention name: Placebo
description: 2 infusions, 2 ml/kg, one the night before operation and one the day after operation
arm group label: Placebo
other name: NaCl 0,9%
other name: Natriumchloride 0,9%
other name: glass container NaCl 0,9% Fresenius Kabi
criteria: 
gender: All
minimum age: 60 Years
maximum age: 80 Years
healthy volunteers: No
last name: A.P.J. Houdijk, Dr.
role: Principal Investigator
affiliation: Medical Center of Alkmaar
facility: 
country: Netherlands
responsible party type: Principal Investigator
investigator affiliation: Medical Center Alkmaar
investigator full name: Alexander P.J. Houdijk
investigator title: Dr.
mesh term: Colonic Neoplasms
mesh term: Tocopherols
mesh term: Antioxidants