<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/NCT03824041</url>
  </required_header>
  <id_info>
    <org_study_id>18-8045H</org_study_id>
    <nct_id>NCT03824041</nct_id>
  </id_info>
  <brief_title>Effects of Aronia Berries on Vascular Endothelial Function and the Gut Microbiota in Middle-Aged/Older Adults</brief_title>
  <official_title>Aronia Berry Supplementation for Improving Vascular Endothelial Dysfunction and Modulating the Gut Microbiota in Middle-Aged/Older Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Colorado State University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Naturex-Dbs</agency>
      <agency_class>Industry</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>
      Aging is the primary risk factor for cardiovascular disease (CVD) largely due to vascular&#xD;
      endothelial dysfunction, a major initial step in the development of atherosclerosis.&#xD;
      Endothelial dysfunction is characterized by impaired endothelium-dependent dilation and is&#xD;
      primarily caused by reduced nitric oxide bioavailability secondary to oxidative stress and&#xD;
      inflammation. Interventions that improve endothelial dysfunction are important for improving&#xD;
      endothelial function and reducing CVD risk in this high-risk population. Aronia melanocarpa,&#xD;
      commonly known as aronia berries or chokeberries, are rich in polyphenols such as&#xD;
      anthocyanins, proanthocyanidins, and phenolic acids. These compounds, and derivatives&#xD;
      resulting from gut microbial and phase II metabolism, have been shown to attenuate oxidative&#xD;
      stress and inflammation, and to improve endothelial function. Aronia berries and other&#xD;
      berries have been shown in numerous studies to have diverse cardiometabolic health effects&#xD;
      including modulation of endothelial function, arterial stiffness, blood pressure, oxidative&#xD;
      stress, and inflammation. In addition, berries, dietary fiber, polyphenols have been shown to&#xD;
      exert positive effects on the gut microbiota, which may mediate improvements in&#xD;
      cardiovascular health. Recently, we have demonstrated that modulation of the gut microbiota&#xD;
      is associated with improvements in vascular dysfunction. The primary goal of the currently&#xD;
      proposed research is to assess the efficacy and dose-dependent response of an aronia full&#xD;
      spectrum dietary supplement to improve endothelial function in middle-aged/older men and&#xD;
      postmenopausal women. A secondary goal is to determine whether aronia full spectrum&#xD;
      modulation of the gut microbiota is associated with improvements in endothelial function.&#xD;
      Other functional and biochemical measures of cardiovascular health, oxidative stress,&#xD;
      inflammation, and polyphenol metabolism will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 11, 2019</start_date>
  <completion_date type="Actual">July 26, 2021</completion_date>
  <primary_completion_date type="Actual">July 26, 2021</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline reactive hyperemia index (RHI) after 6 weeks consumption</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on RHI measured by EndoPAT</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gut microbiota analysis</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on stool sample microbial populations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on brachial and aortic blood pressure measured by SphygmoCor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Augmentation index</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on augmentation index measured by SphygmoCor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal health</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on gastrointestinal health using a validated questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse wave velocity</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on aortic arterial stiffness measured by SphygmoCor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood lipids</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on blood lipid profiles (total cholesterol, HDL, LDL, triglycerides)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood hemoglobin A1c</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on Hemoglobin A1c</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood oxidized LDL</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on oxidized LDL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood ICAM</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on ICAM</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood VCAM</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on VCAM</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Plasma polyphenol metabolites</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on plasma polyphenol metabolites</description>
  </other_outcome>
  <other_outcome>
    <measure>Fecal polyphenol metabolites</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on fecal polyphenol metabolites</description>
  </other_outcome>
  <other_outcome>
    <measure>Urine polyphenol metabolites</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Determine the effects on urine polyphenol metabolites</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Endothelial Dysfunction</condition>
  <condition>Aging</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Formulation containing inert artificially colored maltodextrin, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aronia full spectrum - half dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Formulation containing 50% Aronia full spectrum and 50% placebo, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aronia full spectrum - full dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Formulation of 100% Aronia full spectrum, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Aronia full spectrum - half dose</intervention_name>
    <description>Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)</description>
    <arm_group_label>Aronia full spectrum - half dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Aronia full spectrum - full dose</intervention_name>
    <description>Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)</description>
    <arm_group_label>Aronia full spectrum - full dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Identical formulation as the treatment consisting of colored maltodextrin using artificial colors.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and postmenopausal women (&gt; 1 year from cessation of menstruation)&#xD;
&#xD;
          -  Aged 45-75 years&#xD;
&#xD;
          -  Baseline endothelial dysfunction (RHI ≤ 1.67)&#xD;
&#xD;
          -  Hemoglobin A1C ≤ 6.4%&#xD;
&#xD;
          -  Blood pressure &lt; 129/80 mmHg&#xD;
&#xD;
          -  Total cholesterol &lt; 240 mg/dL&#xD;
&#xD;
          -  LDL cholesterol &lt; 190 mg/dL&#xD;
&#xD;
          -  Triglycerides &lt; 350&#xD;
             mg/dLhttps://register.clinicaltrials.gov/prs/app/template/Home.vm?uid=U00036MD&amp;ts=50&amp;s&#xD;
             id=S0008GBU&amp;cx=gvt3fw&#xD;
&#xD;
          -  Body mass index ≥ 18.5 and &lt; 30 kg/m2&#xD;
&#xD;
          -  Subjects are willing to maintain their normal eating/drinking habits and exercise&#xD;
             habits to avoid changes in body weight over the duration of the study&#xD;
&#xD;
          -  Are able to understand the nature of the study&#xD;
&#xD;
          -  Able and willing to give signed written informed consent&#xD;
&#xD;
          -  Signed informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Individuals taking antihypertensive, lipid-lowering, and/or hormone replacement&#xD;
             medications&#xD;
&#xD;
          -  Diagnosed hypertension, CVD, diabetes, metabolic syndrome, cancer, kidney, liver,&#xD;
             pancreatic disease&#xD;
&#xD;
          -  Obese participants, defined as BMI superior or equal to 30&#xD;
&#xD;
          -  Neuropathy, thrombosis, or past arm trauma or surgery&#xD;
&#xD;
          -  &gt; 3 days/wk vigorous exercise&#xD;
&#xD;
          -  Participating in a weight loss program&#xD;
&#xD;
          -  Weight change &gt; 5% in the past 3 months&#xD;
&#xD;
          -  Current smokers or history of smoking in the last 12 months&#xD;
&#xD;
          -  Heavy drinkers (&gt; 7 drinks/wk for women; &gt;14 drinks/wk for men)&#xD;
&#xD;
          -  Antibiotic use at any point during the study or two months prior to enrollment&#xD;
&#xD;
          -  Allergies to aronia berries or other study materials&#xD;
&#xD;
          -  Unwillingness to maintain normal diet and/or physical activity pattern, or to&#xD;
             discontinue use of dietary supplements for the duration of the study&#xD;
&#xD;
          -  Any reason or condition that in the judgment of the clinical investigator(s) may put&#xD;
             the subject at unacceptable risk or that may preclude the subject from understanding&#xD;
             or complying with the study's requirements&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>75 Years</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>Department of Food Science and Human Nutrition, Colorado State University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Department of Food Science and Human Nutrition, Colorado State University</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80523-1571</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>June 29, 2023</last_update_submitted>
  <last_update_submitted_qc>June 29, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Polyphenols</keyword>
  <keyword>Anthocyanins</keyword>
  <keyword>Vascular function</keyword>
  <keyword>Gut microbiome</keyword>
  <keyword>Gut health</keyword>
  <keyword>Berries</keyword>
  <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/NCT03824041
org study id: 18-8045H
nct id: NCT03824041
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Aging is the primary risk factor for cardiovascular disease (CVD) largely due to vascular
      endothelial dysfunction, a major initial step in the development of atherosclerosis.
      Endothelial dysfunction is characterized by impaired endothelium-dependent dilation and is
      primarily caused by reduced nitric oxide bioavailability secondary to oxidative stress and
      inflammation. Interventions that improve endothelial dysfunction are important for improving
      endothelial function and reducing CVD risk in this high-risk population. Aronia melanocarpa,
      commonly known as aronia berries or chokeberries, are rich in polyphenols such as
      anthocyanins, proanthocyanidins, and phenolic acids. These compounds, and derivatives
      resulting from gut microbial and phase II metabolism, have been shown to attenuate oxidative
      stress and inflammation, and to improve endothelial function. Aronia berries and other
      berries have been shown in numerous studies to have diverse cardiometabolic health effects
      including modulation of endothelial function, arterial stiffness, blood pressure, oxidative
      stress, and inflammation. In addition, berries, dietary fiber, polyphenols have been shown to
      exert positive effects on the gut microbiota, which may mediate improvements in
      cardiovascular health. Recently, we have demonstrated that modulation of the gut microbiota
      is associated with improvements in vascular dysfunction. The primary goal of the currently
      proposed research is to assess the efficacy and dose-dependent response of an aronia full
      spectrum dietary supplement to improve endothelial function in middle-aged/older men and
      postmenopausal women. A secondary goal is to determine whether aronia full spectrum
      modulation of the gut microbiota is associated with improvements in endothelial function.
      Other functional and biochemical measures of cardiovascular health, oxidative stress,
      inflammation, and polyphenol metabolism will be assessed.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Change from baseline reactive hyperemia index (RHI) after 6 weeks consumption
time frame: Baseline and 6 weeks
description: Determine the effects on RHI measured by EndoPAT
measure: Gut microbiota analysis
time frame: Baseline and 6 weeks
description: Determine the effects on stool sample microbial populations
measure: Blood pressure
time frame: Baseline and 6 weeks
description: Determine the effects on brachial and aortic blood pressure measured by SphygmoCor
measure: Augmentation index
time frame: Baseline and 6 weeks
description: Determine the effects on augmentation index measured by SphygmoCor
measure: Gastrointestinal health
time frame: Baseline and 6 weeks
description: Determine the effects on gastrointestinal health using a validated questionnaire
measure: Pulse wave velocity
time frame: Baseline and 6 weeks
description: Determine the effects on aortic arterial stiffness measured by SphygmoCor
measure: Blood lipids
time frame: Baseline and 6 weeks
description: Determine the effects on blood lipid profiles (total cholesterol, HDL, LDL, triglycerides)
measure: Blood hemoglobin A1c
time frame: Baseline and 6 weeks
description: Determine the effects on Hemoglobin A1c
measure: Blood oxidized LDL
time frame: Baseline and 6 weeks
description: Determine the effects on oxidized LDL
measure: Blood ICAM
time frame: Baseline and 6 weeks
description: Determine the effects on ICAM
measure: Blood VCAM
time frame: Baseline and 6 weeks
description: Determine the effects on VCAM
measure: Plasma polyphenol metabolites
time frame: Baseline and 6 weeks
description: Determine the effects on plasma polyphenol metabolites
measure: Fecal polyphenol metabolites
time frame: Baseline and 6 weeks
description: Determine the effects on fecal polyphenol metabolites
measure: Urine polyphenol metabolites
time frame: Baseline and 6 weeks
description: Determine the effects on urine polyphenol metabolites
arm group label: Placebo
arm group type: Placebo Comparator
description: Formulation containing inert artificially colored maltodextrin, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)
arm group label: Aronia full spectrum - half dose
arm group type: Experimental
description: Formulation containing 50% Aronia full spectrum and 50% placebo, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)
arm group label: Aronia full spectrum - full dose
arm group type: Experimental
description: Formulation of 100% Aronia full spectrum, two capsules once a day, in a 500 mg capsule regimen (total intake 1000 mg)
intervention type: Dietary Supplement
intervention name: Aronia full spectrum - half dose
description: Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)
arm group label: Aronia full spectrum - half dose
intervention type: Dietary Supplement
intervention name: Aronia full spectrum - full dose
description: Powdered whole fruit obtained from aronia berries (Aronia melanocarpa)
arm group label: Aronia full spectrum - full dose
intervention type: Dietary Supplement
intervention name: Placebo
description: Identical formulation as the treatment consisting of colored maltodextrin using artificial colors.
arm group label: Placebo
criteria: 
gender: All
minimum age: 45 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sarah A Johnson, PhD, RDN
role: Principal Investigator
affiliation: Department of Food Science and Human Nutrition, Colorado State University
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No