<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/NCT04466761</url>
  </required_header>
  <id_info>
    <org_study_id>1516913</org_study_id>
    <nct_id>NCT04466761</nct_id>
  </id_info>
  <brief_title>Ascending Glycan Dietary Supplementation in Healthy Adults</brief_title>
  <official_title>Phase I Ascending Dose Study of Dietary Supplementation With Glycan Monomers in Healthy Adults</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators will conduct a parallel-group, placebo-controlled, randomized, double-blind&#xD;
      ascending dose Phase I study of dietary supplementation in healthy individuals to evaluate&#xD;
      safety and to determine the pharmacologically effective dose (ED).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 23, 2022</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
  <phase>Phase 1</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Characterize Immunoglobulin fragment crystallization modifications</measure>
    <time_frame>4 Weeks</time_frame>
    <description>Use mass spectrometry and RNA sequencing from subject blood samples to characterize site specific glycosylation on Immunoglobulin A, Immunoglobulin M, and Immunoglobulin G.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Identify the maximum effective dose</measure>
    <time_frame>16 Weeks</time_frame>
    <description>Identify maximum effective dose of dietary supplement in grams/day.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess for potential adverse events</measure>
    <time_frame>2 Months after first dose</time_frame>
    <description>Monitor symptoms, severity, and duration of adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of enzymatic modifications measured in grams by spectrometry</measure>
    <time_frame>6 Months</time_frame>
    <description>The investigators will measure enzymatic changes on glycoproteins in the immune system by spectrometry, i.e., these changes will be measured in grams. Spectometry will allow the investigators to quantify these changes in small detail, and therefore give a better idea of how supplementation can change enzymatic process that then affect the structure, and mass, of glycoproteins.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flow cytometry to determine the effect of dietary supplementation on the immune system</measure>
    <time_frame>6 Months</time_frame>
    <description>Perform flow cytometry on subject blood samples to determine the effect of dietary supplement on immune system. For example, the investigators will note changes to immune cell pro-inflammatory and anti-inflammatory cytokine clusters as translated proteins (measured as height and area of cytokine intensity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transcriptome analysis to determine the effect of dietary supplementation on the immune system</measure>
    <time_frame>6 Months</time_frame>
    <description>Perform transcriptome analysis on subject blood samples to determine the effect of dietary supplement on immune system. For example, the investigators will note changes to immune cell pro-inflammatory and anti-inflammatory cytokine clusters as RNA (measure on a logarithmic scale per number of reads) to determine the effects of supplementation on both gene transcription and translation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">65</enrollment>
  <condition>Healthy Individuals</condition>
  <arm_group>
    <arm_group_label>Experimental: Cohort 1-4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>60% of subjects per cohort will consume 30-90 grams of dietary supplement daily for 4 weeks, with each successive cohort dosage increasing according to a Fibonacci dose escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo: Cohort 1-4</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>40% of subjects per cohort will consume 30-90 grams of daily placebo for 4 weeks with each successive cohort dosage increasing in parallel to the experimental arm.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Monosaccharide Powder</intervention_name>
    <description>Monosaccharide powder dissolved in water.</description>
    <arm_group_label>Experimental: Cohort 1-4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Comparator</intervention_name>
    <description>Placebo (cellulose powder).</description>
    <arm_group_label>Placebo: Cohort 1-4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be 18-45 years of age&#xD;
&#xD;
          -  Patients who are in general good health&#xD;
&#xD;
          -  Body Mass Index (BMI) range of 18.5-25&#xD;
&#xD;
          -  All individuals must have the ability to provide inform consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women who are pregnant, actively nursing, or pregnant within the last year&#xD;
&#xD;
          -  Women who are peri-menopausal or post-menopausal&#xD;
&#xD;
          -  Women with irregular menstrual cycles (more frequently than every 21 days or lasts&#xD;
             longer than 8 days (missed, early, or late periods are also considered signs of an&#xD;
             irregular cycle).&#xD;
&#xD;
          -  Women on hormonal contraception, including birth control, hormonal intrauterine&#xD;
             device, or contraceptive implant&#xD;
&#xD;
          -  Past medical history of an autoimmune condition or malignancy, excluding non-melanoma&#xD;
             skin cancer&#xD;
&#xD;
          -  Individuals with first degree relative with history of an autoimmune condition&#xD;
&#xD;
          -  Individuals with cardiovascular, pulmonary, reproductive, endocrine, metabolic,&#xD;
             neurologic, gastrointestinal, hematologic, or infectious diseases of any kind&#xD;
&#xD;
          -  Individuals with diagnosis of galactosemia or congenital disorders of glycosylation&#xD;
&#xD;
          -  Individuals with phenylketonuria&#xD;
&#xD;
          -  Individuals currently taking prescription medications, or have taken prescription&#xD;
             medications within the last 3 months&#xD;
&#xD;
          -  Individuals currently taking over the counter medications&#xD;
&#xD;
          -  Individuals currently taking or have taken supplements including herbal, protein or&#xD;
             vitamin supplements in the last 3 months (e.g. whey protein, St. John's Wort, green&#xD;
             tea supplements, biotin, creatine supplements), excluding multivitamins or essential&#xD;
             vitamins&#xD;
&#xD;
          -  Individuals with prior history of severe food or drug allergic reactions&#xD;
&#xD;
          -  Individuals with a diagnosis of type I or II diabetes mellitus&#xD;
&#xD;
          -  Individuals with allergic reaction or adverse reaction to shellfish, N-acetyl&#xD;
             glucosamine, galactose, or Spirulina/chlorella/algae supplements&#xD;
&#xD;
          -  Individuals with social history of current use of tobacco, alcohol or other drugs&#xD;
&#xD;
          -  Individuals with dietary restrictions (vegetarians are permitted to participate in the&#xD;
             study) or to whom any of the following dietary habits or characteristics apply (the&#xD;
             following exclusion criteria are placed to minimize variability in diet in our study&#xD;
             population):&#xD;
&#xD;
               -  Actively dieting or trying to lose weight&#xD;
&#xD;
               -  Vegan diet&#xD;
&#xD;
               -  Consume equal to or greater than 2 cups of tea a day&#xD;
&#xD;
               -  Consume equal to or greater than 4 cups of coffee a day&#xD;
&#xD;
               -  Consume equal to or greater than 3 cups of fruit juice a day&#xD;
&#xD;
               -  Practice intensive exercise patterns (marathon training, workouts &gt;4 hours a day)&#xD;
&#xD;
               -  Consume soda or energy drinks of any amount&#xD;
&#xD;
               -  On a carbohydrate-restricted or &quot;Paleo&quot; diet&#xD;
&#xD;
               -  Calorie-restricted diet (less than 20%-25% of maintenance calories)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Emanual Maverakis, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Emanual Maverakis, MD</last_name>
    <phone>916-551-2635</phone>
    <email>emaverakis@ucdavis.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Davis Medical Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95630</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lauren Downing</last_name>
      <phone>916-551-2635</phone>
      <email>dermtrials@ucdavis.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 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>Healthy Adults</keyword>
  <keyword>Dietary supplements</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/NCT04466761
org study id: 1516913
nct id: NCT04466761
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The investigators will conduct a parallel-group, placebo-controlled, randomized, double-blind
      ascending dose Phase I study of dietary supplementation in healthy individuals to evaluate
      safety and to determine the pharmacologically effective dose (ED).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Characterize Immunoglobulin fragment crystallization modifications
time frame: 4 Weeks
description: Use mass spectrometry and RNA sequencing from subject blood samples to characterize site specific glycosylation on Immunoglobulin A, Immunoglobulin M, and Immunoglobulin G.
measure: Identify the maximum effective dose
time frame: 16 Weeks
description: Identify maximum effective dose of dietary supplement in grams/day.
measure: Assess for potential adverse events
time frame: 2 Months after first dose
description: Monitor symptoms, severity, and duration of adverse events.
measure: Quantification of enzymatic modifications measured in grams by spectrometry
time frame: 6 Months
description: The investigators will measure enzymatic changes on glycoproteins in the immune system by spectrometry, i.e., these changes will be measured in grams. Spectometry will allow the investigators to quantify these changes in small detail, and therefore give a better idea of how supplementation can change enzymatic process that then affect the structure, and mass, of glycoproteins.
measure: Flow cytometry to determine the effect of dietary supplementation on the immune system
time frame: 6 Months
description: Perform flow cytometry on subject blood samples to determine the effect of dietary supplement on immune system. For example, the investigators will note changes to immune cell pro-inflammatory and anti-inflammatory cytokine clusters as translated proteins (measured as height and area of cytokine intensity).
measure: Transcriptome analysis to determine the effect of dietary supplementation on the immune system
time frame: 6 Months
description: Perform transcriptome analysis on subject blood samples to determine the effect of dietary supplement on immune system. For example, the investigators will note changes to immune cell pro-inflammatory and anti-inflammatory cytokine clusters as RNA (measure on a logarithmic scale per number of reads) to determine the effects of supplementation on both gene transcription and translation.
arm group label: Experimental: Cohort 1-4
arm group type: Experimental
description: 60% of subjects per cohort will consume 30-90 grams of dietary supplement daily for 4 weeks, with each successive cohort dosage increasing according to a Fibonacci dose escalation.
arm group label: Placebo: Cohort 1-4
arm group type: Placebo Comparator
description: 40% of subjects per cohort will consume 30-90 grams of daily placebo for 4 weeks with each successive cohort dosage increasing in parallel to the experimental arm.
intervention type: Dietary Supplement
intervention name: Monosaccharide Powder
description: Monosaccharide powder dissolved in water.
arm group label: Experimental: Cohort 1-4
intervention type: Other
intervention name: Placebo Comparator
description: Placebo (cellulose powder).
arm group label: Placebo: Cohort 1-4
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Emanual Maverakis, MD
role: Principal Investigator
affiliation: University of California, Davis
last name: Emanual Maverakis, MD
phone: 916-551-2635
email: emaverakis@ucdavis.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor
sharing ipd: No