<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/NCT01727895</url>
  </required_header>
  <id_info>
    <org_study_id>Betaglucan_immunity</org_study_id>
    <nct_id>NCT01727895</nct_id>
  </id_info>
  <brief_title>Effects of Orally Administered Beta-glucan on Leukocyte Function in Humans</brief_title>
  <acronym>BG</acronym>
  <official_title>Effects of Orally Administered Beta-glucan on Leukocyte Function in Humans, a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Radboud University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Radboud University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test wether orally administered Beta-glucan has systemic&#xD;
      effects in humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The immunostimulatory properties of mushrooms have been recognized for centuries, and&#xD;
      &quot;medicinal&quot; mushrooms are still widely used in alternative medicine all over the world.&#xD;
      Although a number of fungal components have been implicated in these properties, Beta-glucans&#xD;
      have attracted the most attention. However, although Beta-glucans are widely used as a health&#xD;
      food supplement, their immunomodulatory effects after administration in humans have not yet&#xD;
      been determined.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2013</start_date>
  <completion_date type="Actual">July 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</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>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs)</measure>
    <time_frame>up to 21 days</time_frame>
    <description>The primary objective of the study is to evaluate the systemic effects of orally administered Beta-glucan on innate immune responses of leukocytes. The effects of Beta-glucan will be determined by measuring the ex vivo responsiveness of leukocytes to various inflammatory stimuli as a surrogate marker of the antimicrobial response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>• Production of Other Cytokines (TNF-α, Interleukin (IL)-6, IL-10, IL-1β, IL-17, IL-22, Interferon (IFN)-γ) by Leukocytes ex Vivo Stimulated With Various Stimuli (Including LPS, Pam3Cys, Mycobacterium Tuberculosis, Poly(I:C), Candida, Staph Aureus)</measure>
    <time_frame>days 0, 6, 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• the Absorbance of Orally Administered Beta-glucan Into the Blood Compartment, Measured by ELISA</measure>
    <time_frame>Days 0, 6, 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Transcriptional Pathways (by Use of Microarrays) With Focus on Inflammatory Pathways.</measure>
    <time_frame>Days 0, 6, 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• Changes in Phenotype and Gene Expression Caused by Mechanisms Other Than Changes in the Underlying DNA Sequence (Epigenetic Modifications)</measure>
    <time_frame>Days 0, 6, 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• the Leukocyte Capacity to Phagocytose and Kill the Fungal Pathogen Candida Albicans (Antifungal Activity).</measure>
    <time_frame>Days 0, 6, 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>the Composition of Faecal Microbiota</measure>
    <time_frame>Days 0, 6, 21</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Immunologic Deficiency Syndromes</condition>
  <arm_group>
    <arm_group_label>Beta-glucan</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Beta-glucan (Glucan #300®)</intervention_name>
    <arm_group_label>Beta-glucan</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
          -  Age ≥18&#xD;
&#xD;
          -  Healthy males&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of allergy or intolerance to Beta-glucan&#xD;
&#xD;
          -  Use of any medication&#xD;
&#xD;
          -  Participation in a drug trial or donation of blood 3 months prior to Beta-glucan&#xD;
             administration&#xD;
&#xD;
          -  Use of antibiotics, norit, laxatives (up till 6 months prior to inclusion),&#xD;
             cholestyramine, acid burn inhibitors or immune suppressive agents (up till 3 months&#xD;
             prior to inclusion), and pre- and probiotics (up till 1 month prior to inclusion).&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>36 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mihai Netea, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Radboud University Nijmegen Medical Centre, The Netherlands</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Radboud University Nijmegen Medical Centre</name>
      <address>
        <city>Nijmegen</city>
        <zip>6500 HB</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>November 12, 2012</study_first_submitted>
  <study_first_submitted_qc>November 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 16, 2012</study_first_posted>
  <results_first_submitted>July 1, 2014</results_first_submitted>
  <results_first_submitted_qc>July 1, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 31, 2014</results_first_posted>
  <last_update_submitted>July 1, 2014</last_update_submitted>
  <last_update_submitted_qc>July 1, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 31, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Betaglucan, immune modulation, immunoparalysis, immune suppression</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunologic Deficiency Syndromes</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Recruitment took place from April until May 2013 in the Radboud University Medical Centre Nijmegen.</recruitment_details>
      <pre_assignment_details>Exclusion of subjects was based on pre-defined exclusion criteria or the unability of subjects to comply with the study time schedule.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Beta-glucan</title>
          <description>Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.&#xD;
Beta-glucan (Glucan #300®)</description>
        </group>
        <group group_id="P2">
          <title>Control Group</title>
          <description>No intervention</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Beta-glucan</title>
          <description>Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.&#xD;
Beta-glucan (Glucan #300®)</description>
        </group>
        <group group_id="B2">
          <title>Control Group</title>
          <description>No intervention</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="15"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20" lower_limit="19" upper_limit="22"/>
                    <measurement group_id="B2" value="20" lower_limit="19" upper_limit="24"/>
                    <measurement group_id="B3" value="20" lower_limit="19" upper_limit="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>TNF-α Secretion by ex Vivo LPS-Stimulated Peripheral Blood mononuclear cells</title>
          <units>pg/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="691" lower_limit="276" upper_limit="2649"/>
                    <measurement group_id="B2" value="749" lower_limit="287" upper_limit="1160"/>
                    <measurement group_id="B3" value="720" lower_limit="282" upper_limit="1905"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs)</title>
        <description>The primary objective of the study is to evaluate the systemic effects of orally administered Beta-glucan on innate immune responses of leukocytes. The effects of Beta-glucan will be determined by measuring the ex vivo responsiveness of leukocytes to various inflammatory stimuli as a surrogate marker of the antimicrobial response</description>
        <time_frame>up to 21 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Beta-glucan</title>
            <description>Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.&#xD;
Beta-glucan (Glucan #300®)</description>
          </group>
          <group group_id="O2">
            <title>Control Group</title>
            <description>No intervention</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs)</title>
          <description>The primary objective of the study is to evaluate the systemic effects of orally administered Beta-glucan on innate immune responses of leukocytes. The effects of Beta-glucan will be determined by measuring the ex vivo responsiveness of leukocytes to various inflammatory stimuli as a surrogate marker of the antimicrobial response</description>
          <units>pg/ml</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="691" lower_limit="276" upper_limit="2649"/>
                    <measurement group_id="O2" value="749" lower_limit="287" upper_limit="1160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>• Production of Other Cytokines (TNF-α, Interleukin (IL)-6, IL-10, IL-1β, IL-17, IL-22, Interferon (IFN)-γ) by Leukocytes ex Vivo Stimulated With Various Stimuli (Including LPS, Pam3Cys, Mycobacterium Tuberculosis, Poly(I:C), Candida, Staph Aureus)</title>
        <time_frame>days 0, 6, 21</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>• the Absorbance of Orally Administered Beta-glucan Into the Blood Compartment, Measured by ELISA</title>
        <time_frame>Days 0, 6, 21</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>• Transcriptional Pathways (by Use of Microarrays) With Focus on Inflammatory Pathways.</title>
        <time_frame>Days 0, 6, 21</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>• Changes in Phenotype and Gene Expression Caused by Mechanisms Other Than Changes in the Underlying DNA Sequence (Epigenetic Modifications)</title>
        <time_frame>Days 0, 6, 21</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>• the Leukocyte Capacity to Phagocytose and Kill the Fungal Pathogen Candida Albicans (Antifungal Activity).</title>
        <time_frame>Days 0, 6, 21</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>the Composition of Faecal Microbiota</title>
        <time_frame>Days 0, 6, 21</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Beta-glucan</title>
          <description>Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.&#xD;
Beta-glucan (Glucan #300®)</description>
        </group>
        <group group_id="E2">
          <title>Control Group</title>
          <description>No intervention</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Flare of acne, one week after discontinuation of Beta-glucan intake</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Drs. Jenneke Leentjens</name_or_title>
      <organization>Radboud UMC</organization>
      <phone>0031-243668420</phone>
      <email>Jenneke.Leentjens@radboudumc.nl</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01727895
org study id: Betaglucan_immunity
nct id: NCT01727895
lead sponsor: 
has dmc: Yes
The purpose of this study is to test wether orally administered Beta-glucan has systemic
      effects in humans.
The immunostimulatory properties of mushrooms have been recognized for centuries, and
      "medicinal" mushrooms are still widely used in alternative medicine all over the world.
      Although a number of fungal components have been implicated in these properties, Beta-glucans
      have attracted the most attention. However, although Beta-glucans are widely used as a health
      food supplement, their immunomodulatory effects after administration in humans have not yet
      been determined.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Tumor Necrosis Factor (TNF)-α Secretion by ex Vivo Lipopolysaccharide (LPS)-Stimulated Peripheral Blood Mononuclear Cells (PBMCs)
time frame: up to 21 days
description: The primary objective of the study is to evaluate the systemic effects of orally administered Beta-glucan on innate immune responses of leukocytes. The effects of Beta-glucan will be determined by measuring the ex vivo responsiveness of leukocytes to various inflammatory stimuli as a surrogate marker of the antimicrobial response
measure: • Production of Other Cytokines (TNF-α, Interleukin (IL)-6, IL-10, IL-1β, IL-17, IL-22, Interferon (IFN)-γ) by Leukocytes ex Vivo Stimulated With Various Stimuli (Including LPS, Pam3Cys, Mycobacterium Tuberculosis, Poly(I:C), Candida, Staph Aureus)
time frame: days 0, 6, 21
measure: • the Absorbance of Orally Administered Beta-glucan Into the Blood Compartment, Measured by ELISA
time frame: Days 0, 6, 21
measure: • Transcriptional Pathways (by Use of Microarrays) With Focus on Inflammatory Pathways.
time frame: Days 0, 6, 21
measure: • Changes in Phenotype and Gene Expression Caused by Mechanisms Other Than Changes in the Underlying DNA Sequence (Epigenetic Modifications)
time frame: Days 0, 6, 21
measure: • the Leukocyte Capacity to Phagocytose and Kill the Fungal Pathogen Candida Albicans (Antifungal Activity).
time frame: Days 0, 6, 21
measure: the Composition of Faecal Microbiota
time frame: Days 0, 6, 21
arm group label: Beta-glucan
arm group type: Experimental
description: Commercial available Beta-glucan derived from bakers yeast (S. Cerevisiae): Glucan #300® produced by Transferpoint, Columbia, United States. 2 capsules of 500mg Glucan #300®, daily, for seven days.
arm group label: Control group
arm group type: No Intervention
intervention type: Dietary Supplement
intervention name: Beta-glucan (Glucan #300®)
arm group label: Beta-glucan
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 36 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mihai Netea, MD, PhD
role: Principal Investigator
affiliation: Radboud University Nijmegen Medical Centre, The Netherlands
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Immunologic Deficiency Syndromes
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 