<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/NCT02202265</url>
  </required_header>
  <id_info>
    <org_study_id>48612013</org_study_id>
    <nct_id>NCT02202265</nct_id>
  </id_info>
  <brief_title>Polymorphisms in CD36 and STAT3 Genes and Different Dietary Interventions Among Patients With Coronary Artery Disease</brief_title>
  <acronym>GENUTRI</acronym>
  <official_title>Effect of Polymorphisms in CD36 and STAT3 Genes on Different Dietary Interventions Among Patients With Coronary Artery Disease: a Randomized Clinical Trial With a Nutrigenetic Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto de Cardiologia do Rio Grande do Sul</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Conselho Nacional de Desenvolvimento Científico e Tecnológico</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul, Brazil</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Instituto de Cardiologia do Rio Grande do Sul</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: Cardiovascular diseases are the major health problem worldwide and the&#xD;
      understanding of genetic contributions on the development of cardiovascular diseases is&#xD;
      increasing significantly. The CD36 is a protein associated with uptake of oxidized forms of&#xD;
      LDL and the single nucleotide polymorphism (SNP) rs1761667 A/G in the CD36 gene is correlated&#xD;
      with increased consumption of total fat. The transcription factor STAT3 is released during&#xD;
      the inflammatory acute phase response and the SNP rs8069645 G/A in the STAT3 gene is&#xD;
      associated with abdominal obesity and higher intake of saturated fat. Studies have been shown&#xD;
      the benefits of the Mediterranean diet in secondary prevention of cardiovascular disease and&#xD;
      these dietary patterns have been often studied with nutrigenetic approach; these studies,&#xD;
      however, are often limited to European populations, making it difficult to generalize to&#xD;
      different populations.&#xD;
&#xD;
      Hypothesis: Different dietary approaches may similarly influence in modifying metabolic,&#xD;
      inflammatory and anthropometric profile, especially among patients with coronary arterial&#xD;
      disease (CAD). The genetic interaction with environmental factors such as the nutrient&#xD;
      intake, and the prescription of a different diet according to individual genotype, could&#xD;
      influence the development and/or the treatment of cardiovascular diseases.&#xD;
&#xD;
      Objective: To evaluate the effect of three dietary approaches on metabolic, inflammatory and&#xD;
      anthropometric profile in patients with CAD and possible interactions with polymorphisms in&#xD;
      CD36 and STAT3 genes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A randomized clinical trial with a nutrigenetic approach among patients ≥ 40 years diagnosed&#xD;
      with CAD. Randomization will be made in blocks from a list of random numbers generated by&#xD;
      site www.randomization.org (sealed opaque envelopes). A questionnaire with demographic and&#xD;
      clinical data will be applied; systolic and diastolic blood pressure, waist, hip and neck&#xD;
      circumferences, height and weight will be assessed. Nutrients intake will be assessed through&#xD;
      a food diary. Laboratory evaluation will consist of lipid profile (LDL-cholesterol,&#xD;
      HDL-cholesterol and total cholesterol, serum triglycerides), glycemic profile (fasting plasma&#xD;
      glucose, glycated hemoglobin) and inflammatory profile (high-sensitivity C-reactive protein,&#xD;
      fibrinogen, TNF-alpha, interleukin-6 and interleukin-10). Genotyping will be made by TaqMan&#xD;
      SNP Genotyping Assay®. Patients will be randomized in three groups: Group 1 Intervention&#xD;
      [Supplementation with nuts (SN)]: standard dietary guidelines + 30g of nuts a day; Group 2&#xD;
      Intervention [Supplementation with olive oil (SAO)]: standard dietary guidelines + 30ml of&#xD;
      olive oil a day; Group 3 [Control diet (CO)]: standard dietary guidelines. Patients will be&#xD;
      followed for three months (12 weeks) and the primary endpoint will be the change in&#xD;
      LDL-cholesterol. The follow-up visits will be made at 30 days, 60 days and 90 days (final&#xD;
      visit).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Actual">June 17, 2016</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>LDL</measure>
    <time_frame>twelve weeks</time_frame>
    <description>LDL-cholesterol, in mg/dL</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>TC</measure>
    <time_frame>twelve weeks</time_frame>
    <description>total cholesterol (TC), in mg/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NHDL</measure>
    <time_frame>twelve weeks</time_frame>
    <description>non-HDL-cholesterol, in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HDL</measure>
    <time_frame>twelve weeks</time_frame>
    <description>HDL-cholesterol, in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TG</measure>
    <time_frame>twelve weeks</time_frame>
    <description>serum triglyceride, in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TyG index</measure>
    <time_frame>twelve weeks</time_frame>
    <description>Triglycerides/fasting glucose index, calculated according to (fasting triglycerides [mg/dL] x fasting glucose [mg/dL])/2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1C</measure>
    <time_frame>twelve weeks</time_frame>
    <description>glycated hemoglobin (HbA1C), in %</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FG</measure>
    <time_frame>twelve weeks</time_frame>
    <description>fasting glucose, in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Insulin</measure>
    <time_frame>twelve weeks</time_frame>
    <description>serum insulin, in UI/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HOMA-IR</measure>
    <time_frame>twelve weeks</time_frame>
    <description>Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated according to fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>inflammatory profile</measure>
    <time_frame>twelve weeks</time_frame>
    <description>CRP-us, in mg/dL; IL-6, in mg/dL; IL-10, in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BW</measure>
    <time_frame>twelve weeks</time_frame>
    <description>body weight, in kg;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI</measure>
    <time_frame>twelve weeks</time_frame>
    <description>body mass index (BMI), in kg/m2, calculated according to weight (kg)/height*height (m)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WC</measure>
    <time_frame>twelve weeks</time_frame>
    <description>waist circumference, in cm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NC</measure>
    <time_frame>twelve weeks</time_frame>
    <description>neck circumference, in cm</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LAP index</measure>
    <time_frame>twelve weeks</time_frame>
    <description>Lipid Accumulation Product Index (in cm.mmol.l), calculated for men: men (waist circumference [WC] - 65) x triglycerides (TG), and women (WC - 58) x TG</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DAAT index</measure>
    <time_frame>twelve weeks</time_frame>
    <description>Deep-Abdominal-Adipose-Tissue Index (in cm2), calculated for men (- 382.9 + [1.09 x weight] + [6.04 x waist circumference (WC)] + [- 2.29 x body mass index (BMI)]) and women (- 278 + [- 0.86 x weight] + [5.19 x WC])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>VAI index</measure>
    <time_frame>twelve weeks</time_frame>
    <description>Visceral Adiposity Index (log), calculated for men (waist circumference (WC)/[39 + (1.88 x body mass index (BMI)) x (triglycerides (TG)/1.03) x (1.31/HDL)]) and women (WC/[36.58 + (1.89 x BMI) x (TG/0.81) x (1.53/HDL)])</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFA</measure>
    <time_frame>twelve weeks</time_frame>
    <description>plasma fatty acids, in percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mon</measure>
    <time_frame>twelve weeks</time_frame>
    <description>plasma monocytes, in percentage</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rs1761667 G&gt;A</measure>
    <time_frame>baseline</time_frame>
    <description>Polymorphism rs1761667 G&gt;A in the CD36 gene</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>rs8069645 A&gt;G</measure>
    <time_frame>baseline</time_frame>
    <description>Polymorphism rs8069645 A&gt;G in the STAT3 gene</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interaction diet * genotype</measure>
    <time_frame>twelve weeks</time_frame>
    <description>Interaction between dietary intervention, rs1761667 and rs8069645</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">204</enrollment>
  <condition>Coronary Artery Disease</condition>
  <arm_group>
    <arm_group_label>Control diet (standard dietary)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive a control diet based on standard dietary guidelines</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Olive oil (30ml a day)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a control diet based on standard dietary guidelines + 30ml of olive oil a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nuts (30g a day)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive a control diet based on standard dietary guidelines plus 30g of nuts a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Olive oil</intervention_name>
    <description>30ml a day of olive oil</description>
    <arm_group_label>Olive oil (30ml a day)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nuts</intervention_name>
    <description>30g a day of nuts</description>
    <arm_group_label>Nuts (30g a day)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Control diet</intervention_name>
    <description>Diet based on standard guidelines</description>
    <arm_group_label>Control diet (standard dietary)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed with coronary arterial disease.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Psychiatric disease;&#xD;
&#xD;
          -  Morbid obesity (BMI ≥ 40mg/m2);&#xD;
&#xD;
          -  Expectancy of life less than 6 months;&#xD;
&#xD;
          -  Pregnancy or lactation;&#xD;
&#xD;
          -  Renal failure (in dialysis);&#xD;
&#xD;
          -  Congestive heart failure;&#xD;
&#xD;
          -  Prior organ transplantation;&#xD;
&#xD;
          -  Patients in wheelchair;&#xD;
&#xD;
          -  Use of vitamin/nutritional supplements;&#xD;
&#xD;
          -  Chronic use of non steroidal anti-inflammatory drugs;&#xD;
&#xD;
          -  Participation in another experimental study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aline Marcadenti, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vera L Portal, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Melissa M Markoski, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Instituto de Cardiologia/Fundação Universitária de Cardiologia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Alexandre S Quadros, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Instituto de Cardiologia/Fundação Universitária de Cardiologia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC)</name>
      <address>
        <city>Porto Alegre</city>
        <state>Rio Grande Do Sul</state>
        <zip>90.620-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>September 8, 2020</last_update_submitted>
  <last_update_submitted_qc>September 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Heart Diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Disease</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/NCT02202265
org study id: 48612013
nct id: NCT02202265
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Background: Cardiovascular diseases are the major health problem worldwide and the
      understanding of genetic contributions on the development of cardiovascular diseases is
      increasing significantly. The CD36 is a protein associated with uptake of oxidized forms of
      LDL and the single nucleotide polymorphism (SNP) rs1761667 A/G in the CD36 gene is correlated
      with increased consumption of total fat. The transcription factor STAT3 is released during
      the inflammatory acute phase response and the SNP rs8069645 G/A in the STAT3 gene is
      associated with abdominal obesity and higher intake of saturated fat. Studies have been shown
      the benefits of the Mediterranean diet in secondary prevention of cardiovascular disease and
      these dietary patterns have been often studied with nutrigenetic approach; these studies,
      however, are often limited to European populations, making it difficult to generalize to
      different populations.

      Hypothesis: Different dietary approaches may similarly influence in modifying metabolic,
      inflammatory and anthropometric profile, especially among patients with coronary arterial
      disease (CAD). The genetic interaction with environmental factors such as the nutrient
      intake, and the prescription of a different diet according to individual genotype, could
      influence the development and/or the treatment of cardiovascular diseases.

      Objective: To evaluate the effect of three dietary approaches on metabolic, inflammatory and
      anthropometric profile in patients with CAD and possible interactions with polymorphisms in
      CD36 and STAT3 genes.
A randomized clinical trial with a nutrigenetic approach among patients ≥ 40 years diagnosed
      with CAD. Randomization will be made in blocks from a list of random numbers generated by
      site www.randomization.org (sealed opaque envelopes). A questionnaire with demographic and
      clinical data will be applied; systolic and diastolic blood pressure, waist, hip and neck
      circumferences, height and weight will be assessed. Nutrients intake will be assessed through
      a food diary. Laboratory evaluation will consist of lipid profile (LDL-cholesterol,
      HDL-cholesterol and total cholesterol, serum triglycerides), glycemic profile (fasting plasma
      glucose, glycated hemoglobin) and inflammatory profile (high-sensitivity C-reactive protein,
      fibrinogen, TNF-alpha, interleukin-6 and interleukin-10). Genotyping will be made by TaqMan
      SNP Genotyping Assay®. Patients will be randomized in three groups: Group 1 Intervention
      [Supplementation with nuts (SN)]: standard dietary guidelines + 30g of nuts a day; Group 2
      Intervention [Supplementation with olive oil (SAO)]: standard dietary guidelines + 30ml of
      olive oil a day; Group 3 [Control diet (CO)]: standard dietary guidelines. Patients will be
      followed for three months (12 weeks) and the primary endpoint will be the change in
      LDL-cholesterol. The follow-up visits will be made at 30 days, 60 days and 90 days (final
      visit).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: LDL
time frame: twelve weeks
description: LDL-cholesterol, in mg/dL
measure: TC
time frame: twelve weeks
description: total cholesterol (TC), in mg/dL)
measure: NHDL
time frame: twelve weeks
description: non-HDL-cholesterol, in mg/dL
measure: HDL
time frame: twelve weeks
description: HDL-cholesterol, in mg/dL
measure: TG
time frame: twelve weeks
description: serum triglyceride, in mg/dL
measure: TyG index
time frame: twelve weeks
description: Triglycerides/fasting glucose index, calculated according to (fasting triglycerides [mg/dL] x fasting glucose [mg/dL])/2
measure: HbA1C
time frame: twelve weeks
description: glycated hemoglobin (HbA1C), in %
measure: FG
time frame: twelve weeks
description: fasting glucose, in mg/dL
measure: Insulin
time frame: twelve weeks
description: serum insulin, in UI/mL
measure: HOMA-IR
time frame: twelve weeks
description: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), calculated according to fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5
measure: inflammatory profile
time frame: twelve weeks
description: CRP-us, in mg/dL; IL-6, in mg/dL; IL-10, in mg/dL
measure: BW
time frame: twelve weeks
description: body weight, in kg;
measure: BMI
time frame: twelve weeks
description: body mass index (BMI), in kg/m2, calculated according to weight (kg)/height*height (m)
measure: WC
time frame: twelve weeks
description: waist circumference, in cm
measure: NC
time frame: twelve weeks
description: neck circumference, in cm
measure: LAP index
time frame: twelve weeks
description: Lipid Accumulation Product Index (in cm.mmol.l), calculated for men: men (waist circumference [WC] - 65) x triglycerides (TG), and women (WC - 58) x TG
measure: DAAT index
time frame: twelve weeks
description: Deep-Abdominal-Adipose-Tissue Index (in cm2), calculated for men (- 382.9 + [1.09 x weight] + [6.04 x waist circumference (WC)] + [- 2.29 x body mass index (BMI)]) and women (- 278 + [- 0.86 x weight] + [5.19 x WC])
measure: VAI index
time frame: twelve weeks
description: Visceral Adiposity Index (log), calculated for men (waist circumference (WC)/[39 + (1.88 x body mass index (BMI)) x (triglycerides (TG)/1.03) x (1.31/HDL)]) and women (WC/[36.58 + (1.89 x BMI) x (TG/0.81) x (1.53/HDL)])
measure: PFA
time frame: twelve weeks
description: plasma fatty acids, in percentage
measure: Mon
time frame: twelve weeks
description: plasma monocytes, in percentage
measure: rs1761667 G>A
time frame: baseline
description: Polymorphism rs1761667 G>A in the CD36 gene
measure: rs8069645 A>G
time frame: baseline
description: Polymorphism rs8069645 A>G in the STAT3 gene
measure: Interaction diet * genotype
time frame: twelve weeks
description: Interaction between dietary intervention, rs1761667 and rs8069645
arm group label: Control diet (standard dietary)
arm group type: Active Comparator
description: Patients will receive a control diet based on standard dietary guidelines
arm group label: Olive oil (30ml a day)
arm group type: Experimental
description: Patients will receive a control diet based on standard dietary guidelines + 30ml of olive oil a day
arm group label: Nuts (30g a day)
arm group type: Experimental
description: Patients will receive a control diet based on standard dietary guidelines plus 30g of nuts a day
intervention type: Dietary Supplement
intervention name: Olive oil
description: 30ml a day of olive oil
arm group label: Olive oil (30ml a day)
intervention type: Dietary Supplement
intervention name: Nuts
description: 30g a day of nuts
arm group label: Nuts (30g a day)
intervention type: Dietary Supplement
intervention name: Control diet
description: Diet based on standard guidelines
arm group label: Control diet (standard dietary)
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Aline Marcadenti, PhD
role: Principal Investigator
affiliation: Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC)
last name: Vera L Portal, PhD
role: Study Director
affiliation: Instituto de Cardiologia/Fundação Universitária de Cardiologia (IC/FUC)
last name: Melissa M Markoski, PhD
role: Study Director
affiliation: Instituto de Cardiologia/Fundação Universitária de Cardiologia
last name: Alexandre S Quadros, PhD
role: Study Director
affiliation: Instituto de Cardiologia/Fundação Universitária de Cardiologia
facility: 
country: Brazil
responsible party type: Sponsor
mesh term: Coronary Artery Disease
mesh term: Myocardial Ischemia
mesh term: Coronary Disease