<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/NCT04419948</url>
  </required_header>
  <id_info>
    <org_study_id>79549/16-05-2019</org_study_id>
    <nct_id>NCT04419948</nct_id>
  </id_info>
  <brief_title>Oleocanthal Rich Olive Oil Acute Effects on Hyperglycemia and Platelet Activation in T2DM</brief_title>
  <official_title>Acute Effect of Oleocanthal Rich Extra-virgin Olive Oil on Postpranial Hyperglycemia and Platelet Activation of T2DM Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Harokopio University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National and Kapodistrian University of Athens</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Peloponnese</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Harokopio University</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>
      This is a pilot acute dietary intervention study with a randomized cross-over design aiming&#xD;
      to investigate whether acute supplementation of extra virgin olive oil (EVOO) rich in&#xD;
      oleocanthal could attenuate postprandial hyperglycemia and activation of platelets in T2DM&#xD;
      patients. For this reason, non-insulin dependent diabetic patients (10-15) will be randomly&#xD;
      assigned to consume in five different days white bread (50 g CHO) with butter, butter with&#xD;
      ibuprofen, refined olive oil and olive oil with oleocanthal (250 mg/Kg 500 mg/Kg). Blood&#xD;
      samples will be collected pre- and post-intervention up to 4 hours in order to determine&#xD;
      platelet aggregation, postprnadial glycemia, lipemia, inflammation and oxidative stress.&#xD;
&#xD;
      Taking into account the strong anti-inflammatory and anti-platelet properties of oleocanthal,&#xD;
      this study will assess whether oleocanthal-rich olive oils could exert similar effects under&#xD;
      real in vivo conditions in T2DM patients. It will also assess whether these effects are&#xD;
      achieved through improvement of postprandial glycemia and lipemia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 16, 2019</start_date>
  <completion_date type="Anticipated">July 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2020</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>
    <intervention_model_description>Acute postprandial study with a randomized cross-over design</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline of ADP-induced platelet aggregation at 90 min after meals consumption</measure>
    <time_frame>0 and 90 after the consumption of each type of meal</time_frame>
    <description>EC50 (microM) of ADP induced platelet aggregation will be assessed by light transmittance aggregometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of ADP-induced platelet aggregation at 240 min after meals consumption</measure>
    <time_frame>0 and 240 after the consumption of each type of meal</time_frame>
    <description>EC50 (microM) of ADP induced platelet aggregation will be assessed by light transmittance aggregometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of TRAP-induced platelet aggregation at 90 min after meals consumption</measure>
    <time_frame>0 and 90 after the consumption of each type of meal</time_frame>
    <description>EC50 (microM) of TRAP induced platelet aggregation will be assessed by light transmittance aggregometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of TRAP-induced platelet aggregation at 240 min after meals consumption</measure>
    <time_frame>0 and 240 after the consumption of each type of meal</time_frame>
    <description>EC50 (microM) of TRAP induced platelet aggregation will be assessed by light transmittance aggregometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of PAF-induced platelet aggregation at 90 min after meals consumption</measure>
    <time_frame>0 and 90 after the consumption of each type of meal</time_frame>
    <description>EC50 (microM) of PAF induced platelet aggregation will be assessed by light transmittance aggregometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of PAF-induced platelet aggregation at 240 min after meals consumption</measure>
    <time_frame>0 and 240 after the consumption of each type of meal</time_frame>
    <description>EC50 (microM) of PAF induced platelet aggregation will be assessed by light transmittance aggregometry</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Glucose</measure>
    <time_frame>0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal</time_frame>
    <description>iAUC of postprandial glucose will be calculated by serum glucose levels (mg/dL) which will be assessed by commercially available kits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Insulin</measure>
    <time_frame>0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal</time_frame>
    <description>iAUC of postprandial insulin will be calculated by serum insulin levels (mIU/L) which will be assessed by commercially available kits</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Triglycerides</measure>
    <time_frame>0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal</time_frame>
    <description>iAUC of postprandial triglycerides will be calculated by serum triglyceride levels (mg/dL) which will be assessed by commercially available kits</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of IL-6</measure>
    <time_frame>0, 60, 120, 180, 240 min after the consumption of each meal</time_frame>
    <description>iAUC of postprandial IL-6 will be calculated by serum IL-6 levels (mg/dL) which will be assessed by commercially available ELISA kits</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental Area Under the Plasma Concentration Versus Time Curve (AUC) of Protein Carbonyls</measure>
    <time_frame>0, 60, 120, 180, 240 min after the consumption of each meal</time_frame>
    <description>iAUC of postprandial protein carbonyls will be calculated by plasma protein carbonyl levels (mg/dL) which will be determined by a photometric assay</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Anticipated">15</enrollment>
  <condition>Diabetes Mellitus, Adult-Onset</condition>
  <condition>Platelet Dysfunction</condition>
  <condition>Postprandial Hyperglycemia</condition>
  <condition>Lipidemia</condition>
  <condition>Inflammation</condition>
  <condition>Oxidative Stress</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100g white bread plus 40ml butter</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Positive control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100g white bread plus 40ml butter and 400mg ibuprofen</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Refined olive oil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100g white bread plus 40ml refined olive oil</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EVOO with moderate concentration of oleocanthal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100g white bread plus 40ml EVOO containing 250 mg/kg oleocanthal</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EVOO with high concentration of oleocanthal</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100g white bread plus 40ml EVOO containing 500 mg/kg oleocanthal</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>White bread</intervention_name>
    <description>White bread (120g) containing 54 g CHO</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>EVOO with high concentration of oleocanthal</arm_group_label>
    <arm_group_label>EVOO with moderate concentration of oleocanthal</arm_group_label>
    <arm_group_label>Positive control</arm_group_label>
    <arm_group_label>Refined olive oil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Butter</intervention_name>
    <description>Butter 39 g</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>Positive control</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Refined olive oil</intervention_name>
    <description>Refined olive oil (40 ml).</description>
    <arm_group_label>Refined olive oil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>EVOO with 250 mg/kg oleocanthal</intervention_name>
    <description>Extra virgin olive oil containing 250 mg/kg oleocanthal.</description>
    <arm_group_label>EVOO with moderate concentration of oleocanthal</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>EVOO with 500 mg/kg oleocanthal</intervention_name>
    <description>Extra virgin olive oil containing 500 mg/kg oleocanthal.</description>
    <arm_group_label>EVOO with high concentration of oleocanthal</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Ibuprofen</intervention_name>
    <description>Ibuprofen 400 mg</description>
    <arm_group_label>Positive control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  adult patients diagnosed with T2DM&#xD;
&#xD;
          -  stable weight the last two months&#xD;
&#xD;
          -  smokers or not&#xD;
&#xD;
          -  no restriction regarding the menopause&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  insulin therapy&#xD;
&#xD;
          -  antiplatelet, anti-coagulant, anti-inflammatory and anti-depressant medication&#xD;
&#xD;
          -  chronic inflammatory disease&#xD;
&#xD;
          -  autoimmune diseases&#xD;
&#xD;
          -  cancer&#xD;
&#xD;
          -  uncontrolled thyroid disease.&#xD;
&#xD;
          -  supplement consumption the last two months&#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_contact>
    <last_name>Tzortzis Nomikos, PhD</last_name>
    <phone>00302109358920</phone>
    <email>tnomikos72@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maria Efthymia Katsa, MSc</last_name>
    <phone>00306977973450</phone>
    <email>merfykatsa@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Nutrition and Dietetics, Harokopio University</name>
      <address>
        <city>Athens</city>
        <state>I Am Not In The U.S. Or Canada</state>
        <zip>17671</zip>
        <country>Greece</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tzortzis Nomikos, PhD</last_name>
      <phone>00302109358920</phone>
      <email>tnomikos@hua.gr</email>
    </contact>
    <contact_backup>
      <last_name>Maria Efthymia Katsa, MSc</last_name>
      <phone>00306977973450</phone>
      <phone_ext>Nomikos</phone_ext>
      <email>tnomikos72@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Tzortzis Nomikos, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria Efthymia Katsa, MSc</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Kleopatra Ketselidi, Bachelor</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <reference>
    <citation>Agrawal K, Melliou E, Li X, Pedersen TL, Wang SC, Magiatis P, Newman JW, Holt RR. Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial. J Funct Foods. 2017 Sep;36:84-93. doi: 10.1016/j.jff.2017.06.046. Epub 2017 Jul 3.</citation>
    <PMID>29904393</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>February 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>June 3, 2020</last_update_submitted>
  <last_update_submitted_qc>June 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Harokopio University</investigator_affiliation>
    <investigator_full_name>Tzortzis Nomikos</investigator_full_name>
    <investigator_title>Assistant Professor of Biochemistry</investigator_title>
  </responsible_party>
  <keyword>type 2 diabetes mellitus</keyword>
  <keyword>diabetic platelet</keyword>
  <keyword>platelet aggregation</keyword>
  <keyword>oxidative stress</keyword>
  <keyword>inflammation</keyword>
  <keyword>postrpandial</keyword>
  <keyword>hyperglycemia</keyword>
  <keyword>extra virgin olive oil</keyword>
  <keyword>oleocanthal</keyword>
  <keyword>polyphenols</keyword>
  <keyword>dyslipidemia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Hyperglycemia</mesh_term>
    <mesh_term>Hyperlipidemias</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ibuprofen</mesh_term>
  </intervention_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/NCT04419948
org study id: 79549/16-05-2019
nct id: NCT04419948
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a pilot acute dietary intervention study with a randomized cross-over design aiming
      to investigate whether acute supplementation of extra virgin olive oil (EVOO) rich in
      oleocanthal could attenuate postprandial hyperglycemia and activation of platelets in T2DM
      patients. For this reason, non-insulin dependent diabetic patients (10-15) will be randomly
      assigned to consume in five different days white bread (50 g CHO) with butter, butter with
      ibuprofen, refined olive oil and olive oil with oleocanthal (250 mg/Kg 500 mg/Kg). Blood
      samples will be collected pre- and post-intervention up to 4 hours in order to determine
      platelet aggregation, postprnadial glycemia, lipemia, inflammation and oxidative stress.

      Taking into account the strong anti-inflammatory and anti-platelet properties of oleocanthal,
      this study will assess whether oleocanthal-rich olive oils could exert similar effects under
      real in vivo conditions in T2DM patients. It will also assess whether these effects are
      achieved through improvement of postprandial glycemia and lipemia.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Acute postprandial study with a randomized cross-over design
primary purpose: Other
masking: Single (Investigator)
measure: Change from baseline of ADP-induced platelet aggregation at 90 min after meals consumption
time frame: 0 and 90 after the consumption of each type of meal
description: EC50 (microM) of ADP induced platelet aggregation will be assessed by light transmittance aggregometry
measure: Change from baseline of ADP-induced platelet aggregation at 240 min after meals consumption
time frame: 0 and 240 after the consumption of each type of meal
description: EC50 (microM) of ADP induced platelet aggregation will be assessed by light transmittance aggregometry
measure: Change from baseline of TRAP-induced platelet aggregation at 90 min after meals consumption
time frame: 0 and 90 after the consumption of each type of meal
description: EC50 (microM) of TRAP induced platelet aggregation will be assessed by light transmittance aggregometry
measure: Change from baseline of TRAP-induced platelet aggregation at 240 min after meals consumption
time frame: 0 and 240 after the consumption of each type of meal
description: EC50 (microM) of TRAP induced platelet aggregation will be assessed by light transmittance aggregometry
measure: Change from baseline of PAF-induced platelet aggregation at 90 min after meals consumption
time frame: 0 and 90 after the consumption of each type of meal
description: EC50 (microM) of PAF induced platelet aggregation will be assessed by light transmittance aggregometry
measure: Change from baseline of PAF-induced platelet aggregation at 240 min after meals consumption
time frame: 0 and 240 after the consumption of each type of meal
description: EC50 (microM) of PAF induced platelet aggregation will be assessed by light transmittance aggregometry
measure: Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Glucose
time frame: 0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal
description: iAUC of postprandial glucose will be calculated by serum glucose levels (mg/dL) which will be assessed by commercially available kits
measure: Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Insulin
time frame: 0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal
description: iAUC of postprandial insulin will be calculated by serum insulin levels (mIU/L) which will be assessed by commercially available kits
measure: Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of Triglycerides
time frame: 0, 15, 30, 60, 90 120, 180, 240 min after the consumption of each meal
description: iAUC of postprandial triglycerides will be calculated by serum triglyceride levels (mg/dL) which will be assessed by commercially available kits
measure: Incremental Area Under the Serum Concentration Versus Time Curve (AUC) of IL-6
time frame: 0, 60, 120, 180, 240 min after the consumption of each meal
description: iAUC of postprandial IL-6 will be calculated by serum IL-6 levels (mg/dL) which will be assessed by commercially available ELISA kits
measure: Incremental Area Under the Plasma Concentration Versus Time Curve (AUC) of Protein Carbonyls
time frame: 0, 60, 120, 180, 240 min after the consumption of each meal
description: iAUC of postprandial protein carbonyls will be calculated by plasma protein carbonyl levels (mg/dL) which will be determined by a photometric assay
arm group label: Control
arm group type: Experimental
description: 100g white bread plus 40ml butter
arm group label: Positive control
arm group type: Experimental
description: 100g white bread plus 40ml butter and 400mg ibuprofen
arm group label: Refined olive oil
arm group type: Experimental
description: 100g white bread plus 40ml refined olive oil
arm group label: EVOO with moderate concentration of oleocanthal
arm group type: Experimental
description: 100g white bread plus 40ml EVOO containing 250 mg/kg oleocanthal
arm group label: EVOO with high concentration of oleocanthal
arm group type: Experimental
description: 100g white bread plus 40ml EVOO containing 500 mg/kg oleocanthal
intervention type: Other
intervention name: White bread
description: White bread (120g) containing 54 g CHO
arm group label: Control
arm group label: EVOO with high concentration of oleocanthal
arm group label: EVOO with moderate concentration of oleocanthal
arm group label: Positive control
arm group label: Refined olive oil
intervention type: Other
intervention name: Butter
description: Butter 39 g
arm group label: Control
arm group label: Positive control
intervention type: Other
intervention name: Refined olive oil
description: Refined olive oil (40 ml).
arm group label: Refined olive oil
intervention type: Other
intervention name: EVOO with 250 mg/kg oleocanthal
description: Extra virgin olive oil containing 250 mg/kg oleocanthal.
arm group label: EVOO with moderate concentration of oleocanthal
intervention type: Other
intervention name: EVOO with 500 mg/kg oleocanthal
description: Extra virgin olive oil containing 500 mg/kg oleocanthal.
arm group label: EVOO with high concentration of oleocanthal
intervention type: Other
intervention name: Ibuprofen
description: Ibuprofen 400 mg
arm group label: Positive control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Tzortzis Nomikos, PhD
phone: 00302109358920
email: tnomikos72@gmail.com
last name: Maria Efthymia Katsa, MSc
phone: 00306977973450
email: merfykatsa@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
country: Greece
citation: Agrawal K, Melliou E, Li X, Pedersen TL, Wang SC, Magiatis P, Newman JW, Holt RR. Oleocanthal-rich extra virgin olive oil demonstrates acute anti-platelet effects in healthy men in a randomized trial. J Funct Foods. 2017 Sep;36:84-93. doi: 10.1016/j.jff.2017.06.046. Epub 2017 Jul 3.
PMID: 29904393
responsible party type: Principal Investigator
investigator affiliation: Harokopio University
investigator full name: Tzortzis Nomikos
investigator title: Assistant Professor of Biochemistry
mesh term: Diabetes Mellitus
mesh term: Hyperglycemia
mesh term: Hyperlipidemias
mesh term: Diabetes Mellitus, Type 2
mesh term: Inflammation
mesh term: Ibuprofen
sharing ipd: No