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/NCT05967741</url>
    </required_header>
    <id_info>
      <org_study_id>2030510</org_study_id>
      <nct_id>NCT05967741</nct_id>
    </id_info>
    <brief_title>The Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation</brief_title>
    <acronym>EASI</acronym>
    <official_title>Randomized Controlled Clinical Trial to Gauge the Effects of Dietary Erythritol on Platelet Reactivity and Vascular Inflammation</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, Davis</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of California, Davis</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 is to conduct a dietary intervention study in which human participants will&#xD;
        consume beverages sweetened with erythritol or aspartame, each for 2 weeks, in a randomized&#xD;
        crossover design&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        There is a strong correlation between plasma erythritol concentrations and adverse&#xD;
        cardiovascular events in high risk individuals. It has also been demonstrated that&#xD;
        consumption of dietary erythritol leads to high levels of plasma erythritol. There is in&#xD;
        vitro evidence that erythritol at comparable concentrations promotes platelet activation.&#xD;
        However, there is no direct evidence that links human consumption of erythritol with the&#xD;
        onset of platelet activation and adhesion leading to inflammation. The investigators seek to&#xD;
        fill this evidence gap by conducting a randomized crossover dietary intervention study in&#xD;
        which human participants will consume beverages sweetened with erythritol or aspartame, each&#xD;
        for two weeks.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 20, 2023</start_date>
    <completion_date type="Anticipated">May 31, 2024</completion_date>
    <primary_completion_date type="Anticipated">April 20, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <intervention_model_description>Randomized crossover study with 2-week washout</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
      <masking_description>Experimental and control beverage are formulated to be similar color, taste and volume.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>P-selectin, a platelet surface marker, assessed as median fluorescence intensity</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in median fluorescence intensity of P-selectin, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in percentage of P-selectin positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in median fluorescence intensity of PAC-1, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in percentage of PAC-1 positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Annexin V, a platelet surface marker, assessed as median fluorescence intensity</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in median fluorescence intensity of annexin V, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in percentage of annexin V positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity</measure>
      <time_frame>6 weeks</time_frame>
      <description>The change in median fluorescence intensity induced by physiologic agonists, an index of platelet reactivity, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Platelet aggregation in response to physiologic agonist, assessed as aggregation/min</measure>
      <time_frame>6 weeks</time_frame>
      <description>The change in aggregation/min induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation</measure>
      <time_frame>6 weeks</time_frame>
      <description>The change in % maximum aggregation induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in platelet/leukocyte aggregate size, an index of platelet-leukocyte interaction, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of E-Selectin</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma E-Selectin in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of sVCAM1</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma sVCAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of sICAM1</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma sICAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of D-dimer</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma D-dimer in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of Platelet factor 4</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma platelet factor 4 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of Fibrinogen</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fibrinogen in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of Prothrombin fragment 1+2</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma prothrombin fragment 1+2 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of Plasmin-antiplasmin complex</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma plasmin-antiplasmin complex in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma concentration of Lp(a)</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma Lp(a) in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Plasma concentration of glucose</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting glucose in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of triglyceride</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting triglyceride in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of cholesterol</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of low density lipoprotein cholesterol</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting low density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of high density lipoprotein cholesterol</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting high density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of apolipoprotein B</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting apolipoprotein B in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of apolipoprotein CIII</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting apolipoprotein CIII in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <other_outcome>
      <measure>Plasma concentration of uric acid</measure>
      <time_frame>6 weeks</time_frame>
      <description>Change in plasma fasting uric acid in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">24</enrollment>
    <condition>Platelet Aggregation, Spontaneous</condition>
    <condition>Vascular Thrombosis</condition>
    <arm_group>
      <arm_group_label>Erythritol-sweetened beverage</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Aspartame-sweetened beverage</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Control beverages will be made from a noncaloric aspartame-sweetened, fruit-flavored drink mix at the concentration needed to match the sweetness (~3 mg aspartame/kg/day) and flavoring of the erythritol beverages on a per volume basis.</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Erythritol</intervention_name>
      <description>Erythritol is a naturally occurring and non-nutritive sugar alcohol that is classified as generally recognized as safe (GRAS)</description>
      <arm_group_label>Erythritol-sweetened beverage</arm_group_label>
      <other_name>Noncaloric sugar alcohol</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Aspartame</intervention_name>
      <description>Aspartame consists of two amino acids, phenylalanine and aspartic acid, and a methyl group. It does not have metabolic effects and has served as the blinded control beverage in the investigators' completed NIH-funded clinical trials.</description>
      <arm_group_label>Aspartame-sweetened beverage</arm_group_label>
      <other_name>Noncaloric sweetener</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  BMI ≥ 27 kg/m2&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  • History of blood clot, transient ischemic attack (TIA), stroke, angina, heart&#xD;
               attack, or peripheral vascular disease, or current cancer diagnosis.&#xD;
  &#xD;
                 -  Pregnant or lactating women&#xD;
  &#xD;
                 -  Current, prior (within 12 months), or anticipated use of medications for&#xD;
                    treatment of hyperlipidemia, high blood pressure or diabetes, or any medication&#xD;
                    that in the opinion of the investigators will confound results.&#xD;
  &#xD;
                 -  Unwilling to forego the use of anti-inflammatory medication during study.&#xD;
  &#xD;
                 -  Unwilling to forego the use of marijuana during the study.&#xD;
  &#xD;
                 -  Use of tobacco.&#xD;
  &#xD;
                 -  Strenuous exerciser (&gt;4 hours/week at a level more vigorous than walking).&#xD;
  &#xD;
                 -  Surgery or medication for weight loss.&#xD;
  &#xD;
                 -  Diet exclusions: Food allergies or dietary restrictions that may undermine&#xD;
                    compliance to dietary protocol, routine ingestion of more than 2 sugar-sweetened&#xD;
                    beverages or 2 alcoholic beverage/day. Unwillingness to consume artificial or&#xD;
                    noncaloric sweeteners. Habitual consumption (&gt;10 gram/day) of beverage or foods&#xD;
                    that contain erythritol. Recent or current weight loss diet.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Kimber L. Stanhope, Ph.D.</last_name>
      <phone>5302190914</phone>
      <email>klstanhope@ucdavis.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Marinelle Nunez, B.S.</last_name>
      <phone>530-752-2146</phone>
      <email>mvnunez@ucdavis.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Ragle Human Nutrition Research Center, University of California, Davis</name>
        <address>
          <city>Davis</city>
          <state>California</state>
          <zip>95616</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Kimber Stanhope, Ph.D.</last_name>
        <phone>530-752-3720</phone>
        <email>klstanhope@ucdavis.edu</email>
      </contact>
      <contact_backup>
        <last_name>Marinelle Nunez, B.S.</last_name>
        <phone>530-752-2146</phone>
        <email>mvnunez@ucdavis.edu</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, Konig M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9. Epub 2023 Feb 27.</citation>
      <PMID>36849732</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 6, 2023</study_first_submitted>
    <study_first_submitted_qc>July 21, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 1, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>platelet activation</keyword>
    <keyword>vascular inflammation</keyword>
    <keyword>erythritol</keyword>
    <keyword>aspartame</keyword>
    <keyword>dietary intervention</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thrombosis</mesh_term>
      <mesh_term>Inflammation</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Erythritol</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</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/NCT05967741
  org study id: 2030510
  nct id: NCT05967741
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The purpose is to conduct a dietary intervention study in which human participants will
        consume beverages sweetened with erythritol or aspartame, each for 2 weeks, in a randomized
        crossover design
  There is a strong correlation between plasma erythritol concentrations and adverse
        cardiovascular events in high risk individuals. It has also been demonstrated that
        consumption of dietary erythritol leads to high levels of plasma erythritol. There is in
        vitro evidence that erythritol at comparable concentrations promotes platelet activation.
        However, there is no direct evidence that links human consumption of erythritol with the
        onset of platelet activation and adhesion leading to inflammation. The investigators seek to
        fill this evidence gap by conducting a randomized crossover dietary intervention study in
        which human participants will consume beverages sweetened with erythritol or aspartame, each
        for two weeks.
  allocation: Randomized
  intervention model: Crossover Assignment
  intervention model description: Randomized crossover study with 2-week washout
  primary purpose: Basic Science
  masking: Triple (Participant, Care Provider, Outcomes Assessor)
  masking description: Experimental and control beverage are formulated to be similar color, taste and volume.
  measure: P-selectin, a platelet surface marker, assessed as median fluorescence intensity
  time frame: 6 weeks
  description: Change in median fluorescence intensity of P-selectin, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: P-selectin, a platelet surface marker, assessed as percentage of P-selectin positive cells
  time frame: 6 weeks
  description: Change in percentage of P-selectin positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as median fluorescence intensity
  time frame: 6 weeks
  description: Change in median fluorescence intensity of PAC-1, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: PAC-1 (GPIIb/IIIa complex), a platelet surface marker, assessed as percentage of PAC-1 positive cells
  time frame: 6 weeks
  description: Change in percentage of PAC-1 positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Annexin V, a platelet surface marker, assessed as median fluorescence intensity
  time frame: 6 weeks
  description: Change in median fluorescence intensity of annexin V, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Annexin V, a platelet surface marker, assessed as percentage of annexin V positive cells
  time frame: 6 weeks
  description: Change in percentage of annexin V positive cells, an index of platelet activation, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Platelet reactivity to physiologic agonist, assessed as change in median fluorescence intensity
  time frame: 6 weeks
  description: The change in median fluorescence intensity induced by physiologic agonists, an index of platelet reactivity, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Platelet aggregation in response to physiologic agonist, assessed as aggregation/min
  time frame: 6 weeks
  description: The change in aggregation/min induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Platelet aggregation in response to physiologic agonist, assessed as percent of maximum aggregation
  time frame: 6 weeks
  description: The change in % maximum aggregation induced by physiologic agonists will be measured by light transmission aggregometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Platelet-leukocyte interaction, assessed as platelet/leukocyte aggregate size by fluorescence mean intensity
  time frame: 6 weeks
  description: Change in platelet/leukocyte aggregate size, an index of platelet-leukocyte interaction, will be measured by flow cytometry in whole blood collected from subjects before and after consuming erythritol-sweetened beverage for 2 weeks and compared with change in whole blood collected before and after consuming aspartame-sweetened beverage for 2 weeks
  measure: Plasma concentration of E-Selectin
  time frame: 6 weeks
  description: Change in plasma E-Selectin in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of sVCAM1
  time frame: 6 weeks
  description: Change in plasma sVCAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of sICAM1
  time frame: 6 weeks
  description: Change in plasma sICAM1 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of D-dimer
  time frame: 6 weeks
  description: Change in plasma D-dimer in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of Platelet factor 4
  time frame: 6 weeks
  description: Change in plasma platelet factor 4 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of Fibrinogen
  time frame: 6 weeks
  description: Change in plasma fibrinogen in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of Prothrombin fragment 1+2
  time frame: 6 weeks
  description: Change in plasma prothrombin fragment 1+2 in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of Plasmin-antiplasmin complex
  time frame: 6 weeks
  description: Change in plasma plasmin-antiplasmin complex in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of Lp(a)
  time frame: 6 weeks
  description: Change in plasma Lp(a) in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of glucose
  time frame: 6 weeks
  description: Change in plasma fasting glucose in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of triglyceride
  time frame: 6 weeks
  description: Change in plasma fasting triglyceride in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of cholesterol
  time frame: 6 weeks
  description: Change in plasma fasting cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of low density lipoprotein cholesterol
  time frame: 6 weeks
  description: Change in plasma fasting low density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of high density lipoprotein cholesterol
  time frame: 6 weeks
  description: Change in plasma fasting high density lipoprotein cholesterol in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of apolipoprotein B
  time frame: 6 weeks
  description: Change in plasma fasting apolipoprotein B in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of apolipoprotein CIII
  time frame: 6 weeks
  description: Change in plasma fasting apolipoprotein CIII in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  measure: Plasma concentration of uric acid
  time frame: 6 weeks
  description: Change in plasma fasting uric acid in subjects before and after sustained consumption of erythritol-sweetened beverage compared with change before and after sustained consumption of aspartame-sweetened beverage
  arm group label: Erythritol-sweetened beverage
  arm group type: Experimental
  description: 1-gram erythritol/kg body weight/day, divided into three beverage servings and fruit-flavored with Kool-Aid® unsweetened drink mix.
  arm group label: Aspartame-sweetened beverage
  arm group type: Placebo Comparator
  description: Control beverages will be made from a noncaloric aspartame-sweetened, fruit-flavored drink mix at the concentration needed to match the sweetness (~3 mg aspartame/kg/day) and flavoring of the erythritol beverages on a per volume basis.
  intervention type: Other
  intervention name: Erythritol
  description: Erythritol is a naturally occurring and non-nutritive sugar alcohol that is classified as generally recognized as safe (GRAS)
  arm group label: Erythritol-sweetened beverage
  other name: Noncaloric sugar alcohol
  intervention type: Other
  intervention name: Aspartame
  description: Aspartame consists of two amino acids, phenylalanine and aspartic acid, and a methyl group. It does not have metabolic effects and has served as the blinded control beverage in the investigators' completed NIH-funded clinical trials.
  arm group label: Aspartame-sweetened beverage
  other name: Noncaloric sweetener
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 70 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Kimber L. Stanhope, Ph.D.
  phone: 5302190914
  email: klstanhope@ucdavis.edu
  last name: Marinelle Nunez, B.S.
  phone: 530-752-2146
  email: mvnunez@ucdavis.edu
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  country: United States
  citation: Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, Haghikia A, Li XS, Wu Y, Saha PP, Demuth I, Konig M, Steinhagen-Thiessen E, Cajka T, Fiehn O, Landmesser U, Tang WHW, Hazen SL. The artificial sweetener erythritol and cardiovascular event risk. Nat Med. 2023 Mar;29(3):710-718. doi: 10.1038/s41591-023-02223-9. Epub 2023 Feb 27.
  PMID: 36849732
  responsible party type: Sponsor
  mesh term: Thrombosis
  mesh term: Inflammation
  mesh term: Erythritol
  sharing ipd: No