<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/NCT03795324</url>
  </required_header>
  <id_info>
    <org_study_id>AppleCor</org_study_id>
    <nct_id>NCT03795324</nct_id>
  </id_info>
  <brief_title>Red-fleshed Apple as a Novel Anthocyanin-biofortified Food to Improve Cardiometabolic Risk Factors.</brief_title>
  <acronym>AppleCor</acronym>
  <official_title>Red-fleshed Apple as a Novel Anthocyanin-biofortified Food to Improve Cardiometabolic Risk Factors: Innovation in Crop and Application to Health.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Rovira i Virgili</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universitat de Lleida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ministerio de Ciencia e Innovación, Spain</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Rovira i Virgili</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary aim is to evaluate the added health value of the presence of anthocyanins in the&#xD;
      redlove apple, versus a green apple with a similar matrix, on cardiometabolic risk, and&#xD;
      compare the matrix effect on the bioavailability of anthocyanins, and its effect on&#xD;
      cardiometabolic risk factors, in two different products with a similar phenolic and&#xD;
      anthocyanin content: the redlove apple and an aronia drink.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The worldwide high prevalence of cardiovascular disease (CVD) requires lifestyle changes and&#xD;
      new dietary prevention strategies based on the increased intake of foods rich in bioactive&#xD;
      compounds, as they are considered as key mediators in the improvement of CVD risk factors.&#xD;
&#xD;
      Regarding the health impact on anthocyanins in cardiometalic risk factors and CVD, it has&#xD;
      been reported that the dietary intake of anthocyanidins, among other classes of flavonoids,&#xD;
      is inversely associated with the risk of CVD in both European and US population. A recent&#xD;
      systematic review of human randomized controlled trials assessing the impact of anthocyanins&#xD;
      on CVD markers concluded that one of the main modulated outcomes is the decrease of serum&#xD;
      LDLc. However, diet does not appear to be sufficient to guarantee the necessary intake to&#xD;
      obtain the health benefits specified. Due to previous positive results, a new dietetic&#xD;
      strategy based on biofortification to enhance the levels of phenolic compounds is proposed in&#xD;
      the present project.&#xD;
&#xD;
      The primary aim is to evaluate the added health value of the presence of anthocyanins in the&#xD;
      redlove apple, versus a green apple with a similar matrix, on cardiometabolic risk, and&#xD;
      compare the matrix effect on the bioavailability of anthocyanins and its effect on&#xD;
      cardiometabolic risk factors, in two different products with a similar phenolic and&#xD;
      anthocyanin content: the redlove apple and an aronia drink.&#xD;
&#xD;
      Participants will be 120 free-living volunteers (men and women) with high LDL-cholesterol&#xD;
      levels (LDL-cholesterol levels ≥115 mg/dl and ≥190 mg/dl) who will be assigned to one of the&#xD;
      three arms for 6-week period of dietary treatment. The design of the intervention study is&#xD;
      controlled, parallel and randomized. The intervention will combine acute (post-prandial) and&#xD;
      chronic effects.&#xD;
&#xD;
      The sample size was computed to be sufficient to detect differences between treatment groups&#xD;
      regarding the evolution in time of LDL-cholesterol levels. Justification of chosen sample&#xD;
      size is based on assuming a 0.50mmol/l (approximately 15%) post-intervention difference of&#xD;
      LDL-cholesterol and a 0.72mmol/l Standard deviation (SD), with α=0.05 and 1-β=0.08 a minimum&#xD;
      of 22 participants were required. However the sample size will be 40 participants for arm, in&#xD;
      total 120 subjects.&#xD;
&#xD;
      For the acute study, the investigators have chosen n=10 subjects per arm according to the&#xD;
      most studies that have addressed the metabolic effects of a postprandial intervention have&#xD;
      been performed using a very similar number of subjects with statistically good quality&#xD;
      results.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 2019</start_date>
  <completion_date type="Anticipated">February 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in serum LDL-cholesterol (measured in mg/dL)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>Serum lipids will be measured by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland). Then, LDL-cholesterol will be alculated by the Friedewald formula.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in parameters of body composition (weight measured in kg)</measure>
    <time_frame>6 weeks, week 1, week 2, week 4 and week 6</time_frame>
    <description>Trained dieticians measure weight using a body composition analyzer (Tanita SC 330-S; Tanita Corp., Barcelona, Sapin)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Parameters of body composition (height measured in meters)</measure>
    <time_frame>6 weeks, week 1</time_frame>
    <description>Trained dieticians measure height using a well mounted stadiometer (Tanita Leicester Portable; Tanita Corp., Barcelona, Spain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in parameters of body composition (BMI measured in kg/m2)</measure>
    <time_frame>6 weeks, week 1, week 2, week 4 and week 6</time_frame>
    <description>Body mass index (BMI) is calculated as the ratio between measured weight (kg)/and the square of height (m).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in parameters of body composition (waist circumference measured in cm)</measure>
    <time_frame>6 weeks, week 1, week 2, week 4 and week 6</time_frame>
    <description>Waist circumference (WC) is measured at the umbilicus using a 150 cm anthropometric steel measuring tape.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in blood pressure (systolic blood pressure and diastolic blood pressure measured in mmHg)</measure>
    <time_frame>6 weeks, week 1, week 2, week 4 and week 6</time_frame>
    <description>Systolic and diastolic blood pressure (SBP and DBP) are measured twice after 2-5 minutes of patient seated, with one-minute interval in between, using an automatic sphygmomanometer (OMRON HEM-907; Peroxfarma, Barcelona, Spain).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in ischemic reactive hyperemia (IRH measured in perfusion units)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>The endothelial-dependent vasomotor functions will be measured as IRH by a Laser-Doppler linear Periflux 5000 flowmeter (Perimed AB, Järfälla, Stockholm, Sweden)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in lipid plasmatic markers (total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids, Apo B100 and Apo A. All these lipid plasmatic markers will be measured in mg/dL)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>Total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids, Apo B100 and Apo A will be measured by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in glucose markers (glucose and insulin measured in mg/dL)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>measured by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in oxidative markers (LDLox and Endogenous fat soluble antioxidants measured in mg/dL)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>Plasma oxidized LDL measured by ELISA kit (Mercodia AB, Uppsala, Sweden). The analysis of fat-soluble vitamins (vitamin D, alpha-tocopherol, and carotenoids) will be carried out in whole blood with DBS cards. The determinations will be performed by ultra-performance liquid chromatography (UPLC) coupled to photodiode array (PDA) and tandem mass spectrometry (MS/MS) detectors.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in inflammation markers (c-reactive protein and serum endothelin-1 measured in mg/dL)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>Serum high sensitive C reactive measured by standardized methods in a Cobas Mira Plus autoanalyzer (Roche Diagnostics Systems, Madrid, Spain). Serum endothelin type 1 measured by ELISA kits (R&amp;D Systems, Minneapolis, USA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in dietary compliance markers (Phenolic compounds and metabolites measured in mg/L in 24h urine samples)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>will be analysed by UPLC-MS/MS as previously described.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in faeces metabolites (Short Chain Fatty Acids, bile acids and sterols measured in mg/L in faeces samples)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>will be performed by gas chromatography (GC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in fecal microbiota composition (relative abundance of the identified operational taxonomic units (OTUs) measured as % change from baseline)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>will be studied by sequencing its whole genomic content. Illumina platform will be used to obtain the metagenomics and metatranscriptomics of each sample following previous protocols developed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in lipoprotein profile (number of LDL and HDL particles measured as % change from baseline)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>Number of particles and size LDL and HDL measured by NMR technology, in a Vantera Clinical Analyzer (LipoScience Inc., Raleigh, NC, USA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in cholesterol efflux (measured as % change from baseline)</measure>
    <time_frame>6 weeks, week 1 and week 6</time_frame>
    <description>Cholesterol efflux measured by in vitro assays in Murine J-774A.1 macrophages labeled with TopFluor-Cholesterol, a fluorescent cholesterol probe in which the cholesterol molecule is linked to boron dipyrromethene difluoride (BODIPY) moiety (Avanti Polar Lipids, USA).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>High LDL-cholesterol Levels</condition>
  <arm_group>
    <arm_group_label>Redlove Apple</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Redlove Apple intervention&#xD;
This product is a biofortified cultivar apple with anthocyanins.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Green Apple</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Green Apple intervention&#xD;
This product is a common cultivar apple without anthocyanins.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aronia Drink</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aronia drink intervention&#xD;
This product is an infusion of aronia fruit extract rich in anthocyanin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Redlove Apple intervention</intervention_name>
    <description>The bioactive compounds present in this product are anthocyanins (50mg per 80g of product).It was a 6 weeks nutritional intervention. Volunteers will eat 80g per day of lyophilized redlove apple.</description>
    <arm_group_label>Redlove Apple</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Green Apple intervention</intervention_name>
    <description>It was a 6 weeks nutritional intervention. Volunteers will eat 80g per day of lyophilized green apple.</description>
    <arm_group_label>Green Apple</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Aronia drink intervention</intervention_name>
    <description>The bioactive compounds present in this extract are anthocyanins (50mg per 1L of water).It was a 6 weeks nutritional intervention. Volunteers will drink 1L per day of an aronia drink</description>
    <arm_group_label>Aronia Drink</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women over 18 years old.&#xD;
&#xD;
          -  LDL-cholesterol levels ≥115 mg/dl and ≥190 mg/dl.&#xD;
&#xD;
          -  Sign the informed consent provided before the initial screening visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  LDL-cholesterol levels ≤115 mg/dl and &lt;190 mg/dl.&#xD;
&#xD;
          -  Use of hypolipemiant treatment (drugs and functional foods), or hypoglucaemiant&#xD;
             treatment.&#xD;
&#xD;
          -  Having diabetes mellitus type 1 or type 2.&#xD;
&#xD;
          -  BMI values ≥35kg/m2.&#xD;
&#xD;
          -  Present triglycerides levels ≥350mg/dl.&#xD;
&#xD;
          -  Presenting anemia (hemoglobin ≤13g/dl in men and ≤12g/dl in women).&#xD;
&#xD;
          -  Subjects diagnosed of intestinal disorders such as Chron disease, colitis ulcerous,&#xD;
             celiac disease and irritable bowel syndrome.&#xD;
&#xD;
          -  Present fructose and/or sorbitol and/or gluten intolerance.&#xD;
&#xD;
          -  Present clinical active chronic disease&#xD;
&#xD;
          -  Use of antioxidants supplements.&#xD;
&#xD;
          -  Being pregnant or intending to become pregnant.&#xD;
&#xD;
          -  Be in breastfeeding period.&#xD;
&#xD;
          -  Present chronic alcoholism.&#xD;
&#xD;
          -  Tobacco use.&#xD;
&#xD;
          -  Participate in or have participated in a clinical trial or nutritional intervention&#xD;
             study in the last 30 days prior to inclusion in the study.&#xD;
&#xD;
          -  Being unable to follow the study guidelines.&#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>Rosa Sola, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Rovira i Virgili</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Rosa Solà, Dr</last_name>
    <phone>636 944 723</phone>
    <phone_ext>0034</phone_ext>
    <email>rosa.sola@urv.cat</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Rovira i Virgili</name>
      <address>
        <city>Reus</city>
        <state>Tarragona</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>January 4, 2019</last_update_submitted>
  <last_update_submitted_qc>January 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Rovira i Virgili</investigator_affiliation>
    <investigator_full_name>Rosa Sola</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Anthocyanins</keyword>
  <keyword>apple</keyword>
  <keyword>biofortification</keyword>
  <keyword>cardiometabolic</keyword>
  <keyword>LDL cholesterol</keyword>
  <keyword>polyphenols</keyword>
  <!-- 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/NCT03795324
org study id: AppleCor
nct id: NCT03795324
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The primary aim is to evaluate the added health value of the presence of anthocyanins in the
      redlove apple, versus a green apple with a similar matrix, on cardiometabolic risk, and
      compare the matrix effect on the bioavailability of anthocyanins, and its effect on
      cardiometabolic risk factors, in two different products with a similar phenolic and
      anthocyanin content: the redlove apple and an aronia drink.
The worldwide high prevalence of cardiovascular disease (CVD) requires lifestyle changes and
      new dietary prevention strategies based on the increased intake of foods rich in bioactive
      compounds, as they are considered as key mediators in the improvement of CVD risk factors.

      Regarding the health impact on anthocyanins in cardiometalic risk factors and CVD, it has
      been reported that the dietary intake of anthocyanidins, among other classes of flavonoids,
      is inversely associated with the risk of CVD in both European and US population. A recent
      systematic review of human randomized controlled trials assessing the impact of anthocyanins
      on CVD markers concluded that one of the main modulated outcomes is the decrease of serum
      LDLc. However, diet does not appear to be sufficient to guarantee the necessary intake to
      obtain the health benefits specified. Due to previous positive results, a new dietetic
      strategy based on biofortification to enhance the levels of phenolic compounds is proposed in
      the present project.

      The primary aim is to evaluate the added health value of the presence of anthocyanins in the
      redlove apple, versus a green apple with a similar matrix, on cardiometabolic risk, and
      compare the matrix effect on the bioavailability of anthocyanins and its effect on
      cardiometabolic risk factors, in two different products with a similar phenolic and
      anthocyanin content: the redlove apple and an aronia drink.

      Participants will be 120 free-living volunteers (men and women) with high LDL-cholesterol
      levels (LDL-cholesterol levels ≥115 mg/dl and ≥190 mg/dl) who will be assigned to one of the
      three arms for 6-week period of dietary treatment. The design of the intervention study is
      controlled, parallel and randomized. The intervention will combine acute (post-prandial) and
      chronic effects.

      The sample size was computed to be sufficient to detect differences between treatment groups
      regarding the evolution in time of LDL-cholesterol levels. Justification of chosen sample
      size is based on assuming a 0.50mmol/l (approximately 15%) post-intervention difference of
      LDL-cholesterol and a 0.72mmol/l Standard deviation (SD), with α=0.05 and 1-β=0.08 a minimum
      of 22 participants were required. However the sample size will be 40 participants for arm, in
      total 120 subjects.

      For the acute study, the investigators have chosen n=10 subjects per arm according to the
      most studies that have addressed the metabolic effects of a postprandial intervention have
      been performed using a very similar number of subjects with statistically good quality
      results.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Changes in serum LDL-cholesterol (measured in mg/dL)
time frame: 6 weeks, week 1 and week 6
description: Serum lipids will be measured by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland). Then, LDL-cholesterol will be alculated by the Friedewald formula.
measure: Changes in parameters of body composition (weight measured in kg)
time frame: 6 weeks, week 1, week 2, week 4 and week 6
description: Trained dieticians measure weight using a body composition analyzer (Tanita SC 330-S; Tanita Corp., Barcelona, Sapin)
measure: Parameters of body composition (height measured in meters)
time frame: 6 weeks, week 1
description: Trained dieticians measure height using a well mounted stadiometer (Tanita Leicester Portable; Tanita Corp., Barcelona, Spain).
measure: Changes in parameters of body composition (BMI measured in kg/m2)
time frame: 6 weeks, week 1, week 2, week 4 and week 6
description: Body mass index (BMI) is calculated as the ratio between measured weight (kg)/and the square of height (m).
measure: Changes in parameters of body composition (waist circumference measured in cm)
time frame: 6 weeks, week 1, week 2, week 4 and week 6
description: Waist circumference (WC) is measured at the umbilicus using a 150 cm anthropometric steel measuring tape.
measure: Changes in blood pressure (systolic blood pressure and diastolic blood pressure measured in mmHg)
time frame: 6 weeks, week 1, week 2, week 4 and week 6
description: Systolic and diastolic blood pressure (SBP and DBP) are measured twice after 2-5 minutes of patient seated, with one-minute interval in between, using an automatic sphygmomanometer (OMRON HEM-907; Peroxfarma, Barcelona, Spain).
measure: Changes in ischemic reactive hyperemia (IRH measured in perfusion units)
time frame: 6 weeks, week 1 and week 6
description: The endothelial-dependent vasomotor functions will be measured as IRH by a Laser-Doppler linear Periflux 5000 flowmeter (Perimed AB, Järfälla, Stockholm, Sweden)
measure: Changes in lipid plasmatic markers (total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids, Apo B100 and Apo A. All these lipid plasmatic markers will be measured in mg/dL)
time frame: 6 weeks, week 1 and week 6
description: Total cholesterol, HDL cholesterol, triglycerides, non-esterified fatty acids, Apo B100 and Apo A will be measured by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland).
measure: Changes in glucose markers (glucose and insulin measured in mg/dL)
time frame: 6 weeks, week 1 and week 6
description: measured by standardized enzymatic automated methods in an autoanalyzer (Beckman Coulter-Synchron, Galway, Ireland).
measure: Changes in oxidative markers (LDLox and Endogenous fat soluble antioxidants measured in mg/dL)
time frame: 6 weeks, week 1 and week 6
description: Plasma oxidized LDL measured by ELISA kit (Mercodia AB, Uppsala, Sweden). The analysis of fat-soluble vitamins (vitamin D, alpha-tocopherol, and carotenoids) will be carried out in whole blood with DBS cards. The determinations will be performed by ultra-performance liquid chromatography (UPLC) coupled to photodiode array (PDA) and tandem mass spectrometry (MS/MS) detectors.
measure: Changes in inflammation markers (c-reactive protein and serum endothelin-1 measured in mg/dL)
time frame: 6 weeks, week 1 and week 6
description: Serum high sensitive C reactive measured by standardized methods in a Cobas Mira Plus autoanalyzer (Roche Diagnostics Systems, Madrid, Spain). Serum endothelin type 1 measured by ELISA kits (R&D Systems, Minneapolis, USA).
measure: Changes in dietary compliance markers (Phenolic compounds and metabolites measured in mg/L in 24h urine samples)
time frame: 6 weeks, week 1 and week 6
description: will be analysed by UPLC-MS/MS as previously described.
measure: Changes in faeces metabolites (Short Chain Fatty Acids, bile acids and sterols measured in mg/L in faeces samples)
time frame: 6 weeks, week 1 and week 6
description: will be performed by gas chromatography (GC).
measure: Changes in fecal microbiota composition (relative abundance of the identified operational taxonomic units (OTUs) measured as % change from baseline)
time frame: 6 weeks, week 1 and week 6
description: will be studied by sequencing its whole genomic content. Illumina platform will be used to obtain the metagenomics and metatranscriptomics of each sample following previous protocols developed.
measure: Changes in lipoprotein profile (number of LDL and HDL particles measured as % change from baseline)
time frame: 6 weeks, week 1 and week 6
description: Number of particles and size LDL and HDL measured by NMR technology, in a Vantera Clinical Analyzer (LipoScience Inc., Raleigh, NC, USA).
measure: Changes in cholesterol efflux (measured as % change from baseline)
time frame: 6 weeks, week 1 and week 6
description: Cholesterol efflux measured by in vitro assays in Murine J-774A.1 macrophages labeled with TopFluor-Cholesterol, a fluorescent cholesterol probe in which the cholesterol molecule is linked to boron dipyrromethene difluoride (BODIPY) moiety (Avanti Polar Lipids, USA).
arm group label: Redlove Apple
arm group type: Experimental
description: Redlove Apple intervention
This product is a biofortified cultivar apple with anthocyanins.
arm group label: Green Apple
arm group type: Experimental
description: Green Apple intervention
This product is a common cultivar apple without anthocyanins.
arm group label: Aronia Drink
arm group type: Experimental
description: Aronia drink intervention
This product is an infusion of aronia fruit extract rich in anthocyanin.
intervention type: Other
intervention name: Redlove Apple intervention
description: The bioactive compounds present in this product are anthocyanins (50mg per 80g of product).It was a 6 weeks nutritional intervention. Volunteers will eat 80g per day of lyophilized redlove apple.
arm group label: Redlove Apple
intervention type: Other
intervention name: Green Apple intervention
description: It was a 6 weeks nutritional intervention. Volunteers will eat 80g per day of lyophilized green apple.
arm group label: Green Apple
intervention type: Other
intervention name: Aronia drink intervention
description: The bioactive compounds present in this extract are anthocyanins (50mg per 1L of water).It was a 6 weeks nutritional intervention. Volunteers will drink 1L per day of an aronia drink
arm group label: Aronia Drink
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Rosa Sola, MD, PhD
role: Principal Investigator
affiliation: University Rovira i Virgili
last name: Rosa Solà, Dr
phone: 636 944 723
phone ext: 0034
email: rosa.sola@urv.cat
facility: 
country: Spain
responsible party type: Principal Investigator
investigator affiliation: University Rovira i Virgili
investigator full name: Rosa Sola
investigator title: MD, PhD