xml: <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/NCT05967897</url>
    </required_header>
    <id_info>
      <org_study_id>3647</org_study_id>
      <nct_id>NCT05967897</nct_id>
    </id_info>
    <brief_title>Enhancing the Benefits of Blueberry Polyphenols With Protein</brief_title>
    <official_title>Enhancing the Benefits of Blueberry Polyphenols With Plant and Whey Proteins</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Colorado State University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>United States Department of Agriculture (USDA)</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
    </sponsors>
    <source>Colorado State 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>
        The purpose of this randomized crossover trial is determine whether acute consumption of&#xD;
        blueberries with different proteins from plants (hemp or pea) or dairy (whey) impact the&#xD;
        absorption of blueberry phytochemicals, which could impact the health benefits of&#xD;
        blueberries. A secondary purpose is to understand the role that the gut microbiome may play,&#xD;
        as well as the impact on urine polyphenol metabolites and potential implications for&#xD;
        cardiometabolic health. Researchers will compare four arms: 1) Blueberries; 2) Blueberries +&#xD;
        whey protein; 3) Blueberries + pea protein; and 4) Blueberries + hemp protein.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Polyphenols are a structurally diverse class of secondary metabolites found in plants, with&#xD;
        numerous documented benefits for human health including, but not limited to,&#xD;
        anti-inflammatory, antioxidative and cardiovascular-protective effects. Dietary intake of&#xD;
        polyphenols in the United States is low in comparison to other developed countries due to low&#xD;
        intake of fruits and vegetables. Recent studies suggest fruit and vegetable intake should be&#xD;
        increased by incorporating those foods into snacks and mixed meals as ingredients rather than&#xD;
        standalone food items. Presently, berries comprise 10% of the total fruit intake and 7% of&#xD;
        the total polyphenol intake of American adults. As a versatile food ingredient, berries can&#xD;
        easily be added to foods like smoothies and yogurts as an ingredient to increase intake.&#xD;
  &#xD;
        Low polyphenol intake is an issue exacerbated by poor bioavailability. Consumption does not&#xD;
        necessarily mean that these beneficial compounds are delivered to body tissues, as evidenced&#xD;
        by low levels of detection in blood and accumulation in the lower gastrointestinal tract&#xD;
        after feeding. Bioavailability can be enhanced through the complexation of polyphenols with&#xD;
        proteins, a phenomenon which occurs naturally in complex mixtures including both classes of&#xD;
        nutrients. It has been shown that the complexation of polyphenols with proteins in cow's&#xD;
        milk, known as a &quot;matrix effect&quot;, enhances the polyphenol stability and uptake throughout&#xD;
        digestion. The incorporation of berries into complex food mixtures may not only be an&#xD;
        opportunity for improved health outcomes due to increased polyphenol intake, but also an&#xD;
        effective strategy for ensuring that consumers receive the benefits of the nutrients they&#xD;
        consume.&#xD;
  &#xD;
        It is unknown whether the beneficial matrix effects observed when polyphenols interact with&#xD;
        dairy proteins are exclusive to dairy proteins due to characteristics of high digestibility&#xD;
        or structures which favor phenolic interaction, or if similar effects would be observed with&#xD;
        proteins from other sources. Increasing consumer demand for alternative protein sources for&#xD;
        reasons pertaining to human health and environmental sustainability has introduced a variety&#xD;
        of novel plant-based proteins to the American diet, which may elicit similarly advantageous&#xD;
        matrix effects on the bioavailability of polyphenols depending on their digestibility and&#xD;
        structural characteristics. Understanding protein-polyphenol interactions in novel food&#xD;
        matrices is necessary for the development of food products that promote polyphenol&#xD;
        consumption and bioavailability with the aim to improve human health.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">March 9, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Plasma polyphenol metabolites</measure>
      <time_frame>Change from 0 hours (pre-treatment consumption) to 1 hour post-treatment consumption</time_frame>
      <description>Plasma polyphenol metabolite analysis using mass spectrometry</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma polyphenol metabolites</measure>
      <time_frame>Change from 0 hours (pre-treatment consumption) to 2 hours post-treatment consumption</time_frame>
      <description>Plasma polyphenol metabolite analysis using mass spectrometry</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma polyphenol metabolites</measure>
      <time_frame>Change from 0 hours (pre-treatment consumption) to 4 hours post-treatment consumption</time_frame>
      <description>Plasma polyphenol metabolite analysis using mass spectrometry</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma polyphenol metabolites</measure>
      <time_frame>Change from 0 hours (pre-treatment consumption) to 6 hours post-treatment consumption</time_frame>
      <description>Plasma polyphenol metabolite analysis using mass spectrometry</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Plasma polyphenol metabolites</measure>
      <time_frame>Change from 0 hours (pre-treatment consumption) to 24 hours post-treatment consumption</time_frame>
      <description>Plasma polyphenol metabolite analysis using mass spectrometry</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Urine polyphenol metabolites</measure>
      <time_frame>0 hours (pre-treatment consumption) and 24 hours post-treatment consumption</time_frame>
      <description>Urine polyphenol metabolite analysis using mass spectrometry</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Gut microbial analysis</measure>
      <time_frame>0 hours (pre-treatment consumption) and 24 hours post-treatment consumption</time_frame>
      <description>16S rRNA gene sequencing</description>
    </other_outcome>
    <other_outcome>
      <measure>Blood pressure</measure>
      <time_frame>0 hours (pre-treatment consumption) and 1, 2, 4, and 6 hours post-treatment consumption</time_frame>
      <description>Brachial blood pressure parameters (systolic, diastolic, and pulse pressure)</description>
    </other_outcome>
    <other_outcome>
      <measure>Aortic pressure</measure>
      <time_frame>0 hours (pre-treatment consumption) and 1, 2, 4, and 6 hours post-treatment consumption</time_frame>
      <description>Aortic pressure parameters (systolic pressure, aortic pressure, pulse pressure)</description>
    </other_outcome>
    <other_outcome>
      <measure>Augmentation index</measure>
      <time_frame>0 hours (pre-treatment consumption) and 1, 2, 4, and 6 hours post-treatment consumption</time_frame>
      <description>Augmentation index measured via SphygmoCor Xcel</description>
    </other_outcome>
    <other_outcome>
      <measure>Glucose</measure>
      <time_frame>0 hours (pre-treatment consumption) and 1, 2, 4, 6, and 24 hours post-treatment consumption</time_frame>
      <description>Blood glucose will be assessed using standard assays</description>
    </other_outcome>
    <other_outcome>
      <measure>Insulin</measure>
      <time_frame>0 hours (pre-treatment consumption) and 1, 2, 4, 6, and 24 hours post-treatment consumption</time_frame>
      <description>Blood insulin will be assessed using standard assays</description>
    </other_outcome>
    <other_outcome>
      <measure>Nitric oxide metabolites</measure>
      <time_frame>0 hours (pre-treatment consumption) and 1, 2, 4, 6, and 24 hours post-treatment consumption</time_frame>
      <description>Blood nitric oxide metabolites will be assessed using standard assays</description>
    </other_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Healthy Adults</condition>
    <arm_group>
      <arm_group_label>Blueberries</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Freeze-dried blueberry powder</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Blueberries and Whey Protein</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Freeze-dried blueberry powder and whey protein</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Blueberries and Pea Protein</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Freeze-dried blueberry powder and pea protein</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Blueberries and Hemp Protein</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Freeze-dried blueberry powder and hemp protein</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Blueberries</intervention_name>
      <description>22 g freeze-dried blueberry powder mixed with water</description>
      <arm_group_label>Blueberries</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Blueberries and Whey Protein</intervention_name>
      <description>22 g freeze-dried blueberry powder mixed with whey protein and water</description>
      <arm_group_label>Blueberries and Whey Protein</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Blueberries and Pea Protein</intervention_name>
      <description>22 g freeze-dried blueberry powder mixed with pea protein and water</description>
      <arm_group_label>Blueberries and Pea Protein</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Blueberries and Hemp Protein</intervention_name>
      <description>22 g freeze-dried blueberry powder mixed with hemp protein and water</description>
      <arm_group_label>Blueberries and Hemp Protein</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Aged 18 years or older&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  • Blood levels of HbA1c ≥ 6.5%, total cholesterol ≥ 240 mg/dL, LDL cholesterol ≥ 130&#xD;
               mg/dL, triglycerides ≥ 200 mg/dL&#xD;
  &#xD;
                 -  Are anemic (hemoglobin less than 13.5 g/dL in men and 12.0 g/dL in women)&#xD;
  &#xD;
                 -  Have an average blood pressure greater than or equal to 130/80 mmHg, or have&#xD;
                    diagnosed hypertension, hyperlipidemia, cardiovascular disease, diabetes, cancer,&#xD;
                    kidney, liver, gastrointestinal or pancreatic disease&#xD;
  &#xD;
                 -  Taking blood pressure-, lipid- or glucose-lowering, or hormone replacement&#xD;
                    medications&#xD;
  &#xD;
                 -  Are pregnant or are trying to become pregnant&#xD;
  &#xD;
                 -  Have a body mass index &lt; 18.5 or &gt; 30 kg/m2&#xD;
  &#xD;
                 -  &gt;3 days/week vigorous exercise&#xD;
  &#xD;
                 -  Are not willing to maintain your normal eating/drinking and exercise habits over&#xD;
                    the duration of the study&#xD;
  &#xD;
                 -  History of smoking cigarettes in past 12 months&#xD;
  &#xD;
                 -  Binge and/or heavy drinker (&gt;3 drinks on any given occasion and/or &gt;7 drinks/week&#xD;
                    for women, and &gt;4 drinks on any given occasion and/or &gt;14 drinks/week for men)&#xD;
  &#xD;
                 -  Have allergies or contraindication to study treatments, procedures, or procedure&#xD;
                    supplies&#xD;
  &#xD;
                 -  Unable to attend study visits.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Sarah A Johnson, PhD, RDN</last_name>
      <role>Principal Investigator</role>
      <affiliation>Colorado State University, Department of Food Science and Human Nutrition</affiliation>
    </overall_official>
    <overall_official>
      <last_name>Charlene Van Buiten, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Colorado State University, Department of Food Science and Human Nutrition</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Afsana Khandaker, MBBS, MS</last_name>
      <phone>970-491-0464</phone>
      <email>afsana.khandaker@colostate.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Sarah A Johnson, PhD, RDN</last_name>
      <phone>970-491-3807</phone>
      <email>sarah.johnson@colostate.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Food and Nutrition Clinical Research Laboratory - CSU Gifford Building</name>
        <address>
          <city>Fort Collins</city>
          <state>Colorado</state>
          <zip>80523-1571</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Sarah A Johnson, PhD, RDN</last_name>
        <phone>970-491-3807</phone>
        <email>sarah.johnson@colostate.edu</email>
      </contact>
      <investigator>
        <last_name>Sarah A Johnson, PhD, RDN</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Chima B, Mathews P, Morgan S, Johnson SA, Van Buiten CB. Physicochemical Characterization of Interactions between Blueberry Polyphenols and Food Proteins from Dairy and Plant Sources. Foods. 2022 Sep 14;11(18):2846. doi: 10.3390/foods11182846.</citation>
      <PMID>36140972</PMID>
    </reference>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 22, 2023</study_first_submitted>
    <study_first_submitted_qc>July 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>July 20, 2023</last_update_submitted>
    <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Healthy</keyword>
    <keyword>Adults</keyword>
    <keyword>Blueberries</keyword>
    <keyword>Polyphenols</keyword>
    <keyword>Protein</keyword>
    <keyword>Bioavailability</keyword>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05967897
  org study id: 3647
  nct id: NCT05967897
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this randomized crossover trial is determine whether acute consumption of
        blueberries with different proteins from plants (hemp or pea) or dairy (whey) impact the
        absorption of blueberry phytochemicals, which could impact the health benefits of
        blueberries. A secondary purpose is to understand the role that the gut microbiome may play,
        as well as the impact on urine polyphenol metabolites and potential implications for
        cardiometabolic health. Researchers will compare four arms: 1) Blueberries; 2) Blueberries +
        whey protein; 3) Blueberries + pea protein; and 4) Blueberries + hemp protein.
  Polyphenols are a structurally diverse class of secondary metabolites found in plants, with
        numerous documented benefits for human health including, but not limited to,
        anti-inflammatory, antioxidative and cardiovascular-protective effects. Dietary intake of
        polyphenols in the United States is low in comparison to other developed countries due to low
        intake of fruits and vegetables. Recent studies suggest fruit and vegetable intake should be
        increased by incorporating those foods into snacks and mixed meals as ingredients rather than
        standalone food items. Presently, berries comprise 10% of the total fruit intake and 7% of
        the total polyphenol intake of American adults. As a versatile food ingredient, berries can
        easily be added to foods like smoothies and yogurts as an ingredient to increase intake.
  
        Low polyphenol intake is an issue exacerbated by poor bioavailability. Consumption does not
        necessarily mean that these beneficial compounds are delivered to body tissues, as evidenced
        by low levels of detection in blood and accumulation in the lower gastrointestinal tract
        after feeding. Bioavailability can be enhanced through the complexation of polyphenols with
        proteins, a phenomenon which occurs naturally in complex mixtures including both classes of
        nutrients. It has been shown that the complexation of polyphenols with proteins in cow's
        milk, known as a "matrix effect", enhances the polyphenol stability and uptake throughout
        digestion. The incorporation of berries into complex food mixtures may not only be an
        opportunity for improved health outcomes due to increased polyphenol intake, but also an
        effective strategy for ensuring that consumers receive the benefits of the nutrients they
        consume.
  
        It is unknown whether the beneficial matrix effects observed when polyphenols interact with
        dairy proteins are exclusive to dairy proteins due to characteristics of high digestibility
        or structures which favor phenolic interaction, or if similar effects would be observed with
        proteins from other sources. Increasing consumer demand for alternative protein sources for
        reasons pertaining to human health and environmental sustainability has introduced a variety
        of novel plant-based proteins to the American diet, which may elicit similarly advantageous
        matrix effects on the bioavailability of polyphenols depending on their digestibility and
        structural characteristics. Understanding protein-polyphenol interactions in novel food
        matrices is necessary for the development of food products that promote polyphenol
        consumption and bioavailability with the aim to improve human health.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Single (Outcomes Assessor)
  measure: Plasma polyphenol metabolites
  time frame: Change from 0 hours (pre-treatment consumption) to 1 hour post-treatment consumption
  description: Plasma polyphenol metabolite analysis using mass spectrometry
  measure: Plasma polyphenol metabolites
  time frame: Change from 0 hours (pre-treatment consumption) to 2 hours post-treatment consumption
  description: Plasma polyphenol metabolite analysis using mass spectrometry
  measure: Plasma polyphenol metabolites
  time frame: Change from 0 hours (pre-treatment consumption) to 4 hours post-treatment consumption
  description: Plasma polyphenol metabolite analysis using mass spectrometry
  measure: Plasma polyphenol metabolites
  time frame: Change from 0 hours (pre-treatment consumption) to 6 hours post-treatment consumption
  description: Plasma polyphenol metabolite analysis using mass spectrometry
  measure: Plasma polyphenol metabolites
  time frame: Change from 0 hours (pre-treatment consumption) to 24 hours post-treatment consumption
  description: Plasma polyphenol metabolite analysis using mass spectrometry
  measure: Urine polyphenol metabolites
  time frame: 0 hours (pre-treatment consumption) and 24 hours post-treatment consumption
  description: Urine polyphenol metabolite analysis using mass spectrometry
  measure: Gut microbial analysis
  time frame: 0 hours (pre-treatment consumption) and 24 hours post-treatment consumption
  description: 16S rRNA gene sequencing
  measure: Blood pressure
  time frame: 0 hours (pre-treatment consumption) and 1, 2, 4, and 6 hours post-treatment consumption
  description: Brachial blood pressure parameters (systolic, diastolic, and pulse pressure)
  measure: Aortic pressure
  time frame: 0 hours (pre-treatment consumption) and 1, 2, 4, and 6 hours post-treatment consumption
  description: Aortic pressure parameters (systolic pressure, aortic pressure, pulse pressure)
  measure: Augmentation index
  time frame: 0 hours (pre-treatment consumption) and 1, 2, 4, and 6 hours post-treatment consumption
  description: Augmentation index measured via SphygmoCor Xcel
  measure: Glucose
  time frame: 0 hours (pre-treatment consumption) and 1, 2, 4, 6, and 24 hours post-treatment consumption
  description: Blood glucose will be assessed using standard assays
  measure: Insulin
  time frame: 0 hours (pre-treatment consumption) and 1, 2, 4, 6, and 24 hours post-treatment consumption
  description: Blood insulin will be assessed using standard assays
  measure: Nitric oxide metabolites
  time frame: 0 hours (pre-treatment consumption) and 1, 2, 4, 6, and 24 hours post-treatment consumption
  description: Blood nitric oxide metabolites will be assessed using standard assays
  arm group label: Blueberries
  arm group type: Experimental
  description: Freeze-dried blueberry powder
  arm group label: Blueberries and Whey Protein
  arm group type: Active Comparator
  description: Freeze-dried blueberry powder and whey protein
  arm group label: Blueberries and Pea Protein
  arm group type: Active Comparator
  description: Freeze-dried blueberry powder and pea protein
  arm group label: Blueberries and Hemp Protein
  arm group type: Active Comparator
  description: Freeze-dried blueberry powder and hemp protein
  intervention type: Dietary Supplement
  intervention name: Blueberries
  description: 22 g freeze-dried blueberry powder mixed with water
  arm group label: Blueberries
  intervention type: Dietary Supplement
  intervention name: Blueberries and Whey Protein
  description: 22 g freeze-dried blueberry powder mixed with whey protein and water
  arm group label: Blueberries and Whey Protein
  intervention type: Dietary Supplement
  intervention name: Blueberries and Pea Protein
  description: 22 g freeze-dried blueberry powder mixed with pea protein and water
  arm group label: Blueberries and Pea Protein
  intervention type: Dietary Supplement
  intervention name: Blueberries and Hemp Protein
  description: 22 g freeze-dried blueberry powder mixed with hemp protein and water
  arm group label: Blueberries and Hemp Protein
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Sarah A Johnson, PhD, RDN
  role: Principal Investigator
  affiliation: Colorado State University, Department of Food Science and Human Nutrition
  last name: Charlene Van Buiten, PhD
  role: Principal Investigator
  affiliation: Colorado State University, Department of Food Science and Human Nutrition
  last name: Afsana Khandaker, MBBS, MS
  phone: 970-491-0464
  email: afsana.khandaker@colostate.edu
  last name: Sarah A Johnson, PhD, RDN
  phone: 970-491-3807
  email: sarah.johnson@colostate.edu
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: United States
  citation: Chima B, Mathews P, Morgan S, Johnson SA, Van Buiten CB. Physicochemical Characterization of Interactions between Blueberry Polyphenols and Food Proteins from Dairy and Plant Sources. Foods. 2022 Sep 14;11(18):2846. doi: 10.3390/foods11182846.
  PMID: 36140972
  responsible party type: Sponsor
  sharing ipd: Undecided