<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/NCT02206256</url>
  </required_header>
  <id_info>
    <org_study_id>NL47021.029.13</org_study_id>
    <nct_id>NCT02206256</nct_id>
  </id_info>
  <brief_title>Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function</brief_title>
  <acronym>OLIVIER</acronym>
  <official_title>Omega-3 Fatty Acids in Bariatric Gastric Bypass Surgery: Effect on Liver Volume, Immune Response and Erythrocyte Function</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>
      Gastric bypass surgery is the gold standard in bariatric surgery and is a successful method&#xD;
      to reduce weight in morbidly obese subjects. Patients qualified for gastric bypass surgery&#xD;
      are routinely pre-treated with a low calorie diet in order to reduce liver volume and to&#xD;
      facilitate the approach of the gastro-oesophageal junction. Pre-treatment with omega-3 fatty&#xD;
      acids has similar effects on liver volume, but a prospective comparison of both treatments&#xD;
      has not been performed yet. Morbidly obese patients respond differently to surgical stress,&#xD;
      due to a number of factors. First, obesity is associated with a low-grade inflammatory state&#xD;
      induced by an increased amount of macrophages in adipose tissue. This state is associated&#xD;
      with higher levels of pro-inflammatory cytokines in serum and with a less adequate immune&#xD;
      response to infections. Second, obesity is associated with an altered cortisol metabolism&#xD;
      possibly related to adrenal insufficiency. This could play an important role in the altered&#xD;
      response to surgical stress and postoperative complications in obese subjects. Third, obesity&#xD;
      is associated with altered erythrocyte function, including decreased erythrocyte&#xD;
      deformability and increased aggregation, factors contributing to an impaired&#xD;
      microcirculation.&#xD;
&#xD;
      This study has a number of different aims. First, we will compare pre-treatment with the&#xD;
      standard low calorie diet with omega-3 fatty acids on liver volume in patients qualified for&#xD;
      gastric bypass surgery because of morbid obesity. Second, we will investigate the effect of&#xD;
      omega-3 fatty acids on immune function, the low-inflammatory state of adipose tissue, the&#xD;
      stress response of obese subjects before and erythrocyte function. Third, we will investigate&#xD;
      the effect of gastric bypass surgery by comparing values before surgery with values on the&#xD;
      first postoperative day and 6 months after surgery regarding to immunological parameters,&#xD;
      stress response and erythrocyte function.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 2014</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">November 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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver volume</measure>
    <time_frame>baseline, after treatment</time_frame>
    <description>liver volume of the left hepatic lobe measured by MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peri-operative ex vivo LPS stimulated cytokine production capacity</measure>
    <time_frame>baseline, operation day, postoperative day 1, follow up 6 months</time_frame>
    <description>IL-6, IL-10, TNF-alpha</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Macrophage infiltration in omentum fat biopsies</measure>
    <time_frame>Biopsies during gastric bypass surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erythrocyte function</measure>
    <time_frame>baseline, day of surgery, postoperative day 1, follow up 6 months</time_frame>
    <description>Measurement of erythrocyte deformability and aggregation with LORRCA (laser-assisted optical rotational red cell analyzer)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cortisol response</measure>
    <time_frame>baseline, operation day, postoperative day 1, follow up 6 months</time_frame>
    <description>ACTH stimulation test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum parameters of inflammatory response</measure>
    <time_frame>baseline, operation day, postoperative day 1, follow up 6 months</time_frame>
    <description>IL-6, IL-10, TNF-alpha and C-reactive protein</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of the approach of the gastro-oesophageal junction</measure>
    <time_frame>During gastric bypass surgery</time_frame>
    <description>Surgeons fill out a questionnaire after the gastric bypass surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient satisfaction with intervention</measure>
    <time_frame>After the pre-operative treatment</time_frame>
    <description>Questionnaire</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Morbid Obesity</condition>
  <arm_group>
    <arm_group_label>Low calorie diet</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Low calorie diet 2 weeks pre-operatively</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Omega-3 fatty acid capsules</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>2 times a day 1 capsule for 4 weeks before gastric bypass surgery</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omega-3 fatty acid capsules</intervention_name>
    <description>2 times a day 1 capsule for 4 weeks before gastric bypass surgery</description>
    <arm_group_label>Omega-3 fatty acid capsules</arm_group_label>
    <other_name>purified fish oil</other_name>
    <other_name>omega-3 fatty acids</other_name>
    <other_name>eicosapentoenoic acid (EPA)</other_name>
    <other_name>docosahexaenoic acid (DHA)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Low calorie diet</intervention_name>
    <description>A low calorie diet of 600 kcal/day during 2 weeks, using Modifast or an adjusted normal diet.</description>
    <arm_group_label>Low calorie diet</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Females undergoing laparoscopic gastric bypass surgery because of morbid obesity&#xD;
&#xD;
          -  Age between 18 and 65 years&#xD;
&#xD;
          -  Able to fit in the MRI&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Diabetes mellitus type 1&#xD;
&#xD;
          -  Current history of inflammatory, infectious or malignant disease&#xD;
&#xD;
          -  Daily use of anti-inflammatory drugs&#xD;
&#xD;
          -  Contra-indications for MRI imaging&#xD;
&#xD;
          -  Contra-indications for the use of omega-3 fatty acids&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 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>Rode Kruis Ziekenhuis, Medisch Centrum Alkmaar</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rode Kruis Ziekenhuis</name>
      <address>
        <city>Beverwijk</city>
        <state>Noord Holland</state>
        <zip>1942 LE</zip>
        <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>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 1, 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>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Obesity, Morbid</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/NCT02206256
org study id: NL47021.029.13
nct id: NCT02206256
lead sponsor: 
has dmc: Yes
Gastric bypass surgery is the gold standard in bariatric surgery and is a successful method
      to reduce weight in morbidly obese subjects. Patients qualified for gastric bypass surgery
      are routinely pre-treated with a low calorie diet in order to reduce liver volume and to
      facilitate the approach of the gastro-oesophageal junction. Pre-treatment with omega-3 fatty
      acids has similar effects on liver volume, but a prospective comparison of both treatments
      has not been performed yet. Morbidly obese patients respond differently to surgical stress,
      due to a number of factors. First, obesity is associated with a low-grade inflammatory state
      induced by an increased amount of macrophages in adipose tissue. This state is associated
      with higher levels of pro-inflammatory cytokines in serum and with a less adequate immune
      response to infections. Second, obesity is associated with an altered cortisol metabolism
      possibly related to adrenal insufficiency. This could play an important role in the altered
      response to surgical stress and postoperative complications in obese subjects. Third, obesity
      is associated with altered erythrocyte function, including decreased erythrocyte
      deformability and increased aggregation, factors contributing to an impaired
      microcirculation.

      This study has a number of different aims. First, we will compare pre-treatment with the
      standard low calorie diet with omega-3 fatty acids on liver volume in patients qualified for
      gastric bypass surgery because of morbid obesity. Second, we will investigate the effect of
      omega-3 fatty acids on immune function, the low-inflammatory state of adipose tissue, the
      stress response of obese subjects before and erythrocyte function. Third, we will investigate
      the effect of gastric bypass surgery by comparing values before surgery with values on the
      first postoperative day and 6 months after surgery regarding to immunological parameters,
      stress response and erythrocyte function.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Liver volume
time frame: baseline, after treatment
description: liver volume of the left hepatic lobe measured by MRI
measure: Peri-operative ex vivo LPS stimulated cytokine production capacity
time frame: baseline, operation day, postoperative day 1, follow up 6 months
description: IL-6, IL-10, TNF-alpha
measure: Macrophage infiltration in omentum fat biopsies
time frame: Biopsies during gastric bypass surgery
measure: Erythrocyte function
time frame: baseline, day of surgery, postoperative day 1, follow up 6 months
description: Measurement of erythrocyte deformability and aggregation with LORRCA (laser-assisted optical rotational red cell analyzer)
measure: Cortisol response
time frame: baseline, operation day, postoperative day 1, follow up 6 months
description: ACTH stimulation test
measure: Serum parameters of inflammatory response
time frame: baseline, operation day, postoperative day 1, follow up 6 months
description: IL-6, IL-10, TNF-alpha and C-reactive protein
measure: Assessment of the approach of the gastro-oesophageal junction
time frame: During gastric bypass surgery
description: Surgeons fill out a questionnaire after the gastric bypass surgery
measure: Patient satisfaction with intervention
time frame: After the pre-operative treatment
description: Questionnaire
arm group label: Low calorie diet
arm group type: Active Comparator
description: Low calorie diet 2 weeks pre-operatively
arm group label: Omega-3 fatty acid capsules
arm group type: Active Comparator
description: 2 times a day 1 capsule for 4 weeks before gastric bypass surgery
intervention type: Drug
intervention name: Omega-3 fatty acid capsules
description: 2 times a day 1 capsule for 4 weeks before gastric bypass surgery
arm group label: Omega-3 fatty acid capsules
other name: purified fish oil
other name: omega-3 fatty acids
other name: eicosapentoenoic acid (EPA)
other name: docosahexaenoic acid (DHA)
intervention type: Behavioral
intervention name: Low calorie diet
description: A low calorie diet of 600 kcal/day during 2 weeks, using Modifast or an adjusted normal diet.
arm group label: Low calorie diet
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: A.P.J. Houdijk, Dr.
role: Principal Investigator
affiliation: Rode Kruis Ziekenhuis, Medisch Centrum 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: Obesity, Morbid