<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/NCT03829228</url>
  </required_header>
  <id_info>
    <org_study_id>201875</org_study_id>
    <nct_id>NCT03829228</nct_id>
  </id_info>
  <brief_title>An Evaluation of Proglucamune in the Treatment of Protective Qi Insufficiency</brief_title>
  <official_title>An Evaluation of Proglucamune in the Treatment of Protective Qi</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>USANA Health Sciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Elegant And Olive Health Clinic, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>USANA Health Sciences</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>
      According to Traditional Chinese Medicine (TCM) principle, Protective Qi (PQi) is a one&#xD;
      specific concept of Qi that provides the vital energy of the body. It works primarily on the&#xD;
      body surface as a defensive barrier. In this context, PQi is analogous to anatomical barriers&#xD;
      of the innate immune system located for example, at the skin surface and the mucosal surfaces&#xD;
      of the respiratory and digestive tract. Individuals with PQi Insufficiency are predisposed to&#xD;
      frequent cold and other symptoms caused by invasion of external pathogens (&quot;Wai Xie&quot; or&#xD;
      &quot;external evil&quot; in TCM).&#xD;
&#xD;
      ß-glucan is a polysaccharide that activates macrophage (Dectin-1) and neutrophil (CR3)&#xD;
      receptors, and therefore enhances immune defense at digestive and respiratory mucosa.&#xD;
      Clinical trials have shown its immune activity such as preventing upper respiratory tract&#xD;
      infection (URTI) and Traveler's diarrhea. Notably, ß-glucan is a component of Ganoderma&#xD;
      Luciderm (or Reishi / Lingzhi), one TCM ingredient well-known for improving Qi. Based on this&#xD;
      connection, investigators hypothesized that ß-glucan is the active ingredient in Reishi that&#xD;
      at least partially accounts for Reishi's activity on Qi.&#xD;
&#xD;
      To test our hypothesis, investigators have conducted an uncontrolled pilot trial that&#xD;
      investigated the effect of a commercially available, high ß-glucan containing product,&#xD;
      Proglucamune®, on PQi status. Proglucamune contains ß-glucan from three different natural&#xD;
      sources: Reishi mushroom, Shiitaki mushroom, and Bakers' yeast, each providing ß-glucan that&#xD;
      differs slightly in their molecular structure. Through this pilot investigators sought to&#xD;
      obtain an estimate of the effect size of Proglucamune on PQi that would allow us, via&#xD;
      statistical methods, to estimate the necessary sample size for more definitive future trials.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Unlike mainstream Western medicine (WM), alternative medicines (AM) such as Traditional&#xD;
      Chinese Medicine (TCM), emphasizes individually-differentiated therapies. As such, AM&#xD;
      therapies are normally not tested in clinical studies that statistically demonstrate the&#xD;
      efficacy at the populational level for applicable patients, and this makes it difficult to&#xD;
      objectively evaluate and compare different therapies. The lack of clinical studies stands as&#xD;
      a barrier for the advance of AMs as well as their engagement with WM. In fact, most&#xD;
      researchers view AMs primarily as untapped sources of &quot;active ingredients/compounds&quot; for drug&#xD;
      development, but disregard the rationales under which the therapies were developed. A&#xD;
      &quot;One-Way-Traffic&quot; research paradigm is thus created wherein AM therapies are investigated for&#xD;
      their efficacy by WM standards, whereas the vast potential of employing WM therapies for AM&#xD;
      therapeutics is ignored. In light of this, investigators set up a novel strategy that bridges&#xD;
      TCM and WM, i.e., testing a WM-based therapy by TCM standards through clinical&#xD;
      trial/statistics- based method.&#xD;
&#xD;
      Qi is a central concept of traditional Chinese medicine (TCM) and was first documented in the&#xD;
      oldest TCM writings more than 2000 years ago. Generally speaking, Qi refers to the vital&#xD;
      energy of the body and is derived from two primary sources: 1) inborn Qi (that may be&#xD;
      construed as genetics), and 2) pectoral Qi (can be construed as metabolism). Moreover, Qi&#xD;
      manifests itself in two forms: Nutritive Qi and Protective Qi, which can be understood to&#xD;
      reflect an individual's nutritional state and immune health, respectively. Regarding the&#xD;
      latter, protective Qi functions to defend the body from the invasion of external pathogens.&#xD;
      TCM also emphasizes that Protective Qi works primarily on the body surface as a defensive&#xD;
      barrier. In this context, Protective Qi is analogous to anatomical barriers of the innate&#xD;
      immune system located for example, at the skin surface and the mucosal surfaces of the&#xD;
      respiratory and digestive tract.&#xD;
&#xD;
      TCM has developed a number of methods to strengthen the Qi. Prominent among these is the use&#xD;
      of Reishi, either alone or in combination with other TCM remedies. The use of Reishi was&#xD;
      described in detail in the first TCM pharmacopeia &quot;Compendium of Materia Medica&quot; published in&#xD;
      year 1,600. Nonetheless, although Protective Qi is part of the general Qi, the specific&#xD;
      effect of Reishi on Protective Qi is less documented. Anecdotal reports are available that&#xD;
      claim significant improvement of Protective Qi with Reishi or Reishi-containing formulas&#xD;
      within days. Notably, Western medicine has identified immune-boosting properties of Reishi,&#xD;
      which may explain the Qi enhancing effects of this plant. Specifically, beta-glucan - a&#xD;
      component of Reishi - has been shown to activate macrophage (large white blood cells in the&#xD;
      immune system that destroy bacteria and other harmful substances), neutrophil (type of white&#xD;
      blood cells that are important for protection against infections), and other immunocytes (a&#xD;
      type of cells capable of producing an immune response), and may exhibit particular benefits&#xD;
      among macrophage-rich organs such as the lung, liver and spleen. In fact, ß-glucans from&#xD;
      sources other than Reishi, such as baker's yeast, are able to initiate the same immune&#xD;
      response and clinical benefits.&#xD;
&#xD;
      The overlap of TCM and western medicine concerning the beneficial effects of Reishi for its&#xD;
      Qi enhancing and immune-modulating effects, respectively, has prompted us to investigate&#xD;
      whether or not Reishi, in conjunction with other natural products used in TCM, can enhance an&#xD;
      individual's Protective Qi. More specifically, the objective of the current protocol is to&#xD;
      determine if a commercially available dietary supplement (Proglucamune®, USANA Health&#xD;
      Sciences) containing powdered Reishi and Shitake mushrooms as well as baker's yeast extract,&#xD;
      and which is comprised of 11% ß-glucans by weight, will improve Protective Qi in subjects&#xD;
      diagnosed by practitioners of TCM as having low or insufficient Protective Qi. Specifically,&#xD;
      in this a pilot study, investigators sought to obtain an estimate of the effect size of&#xD;
      Proglucamune on PQi that would allow us, via statistical methods, to estimate the necessary&#xD;
      sample size for more definitive future trials. The trial also aimed to provide information on&#xD;
      individuals who are responsive to Proglucamune treatment (responder), and subsequently&#xD;
      recruit targeted individuals for the follow-up trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 18, 2018</start_date>
  <completion_date type="Actual">June 3, 2018</completion_date>
  <primary_completion_date type="Actual">June 3, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Subjects with Protective Qi Insufficiency</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Given the small sample size in this pilot study and the potential drop-out rate, we did not include a placebo group to control for the placebo effect. Nonetheless, we implemented a &quot;deceptive&quot; double-blinding design, i.e., all on-site care-providers and investigators and all participants were told that this study was placebo controlled, and that each participant had a 50/50 chance of receiving treatment or placebo. This masking helps decreasing the expectation bias from the participants that confound the study result.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Protective Qi Score (PQS) Determined by a Standardized Assessment</measure>
    <time_frame>The change of PQS was obtained by assessment of PQS at each follow-up visit from the baseline (start date). The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
    <description>Protective Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 3 health conditions relevant to PQD (cold frequency, symptoms, and signs). Each condition will be scored on a 1-10 scale based on a set of standardized criteria. The sub-scores will be weighted to arrive at a final PQS. So this PQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the PQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change of Protective Qi (PQi) Status Determined by Traditional TCM Assessment</measure>
    <time_frame>PQi status was determined at the baseline (start date) and each follow-up visit. The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
    <description>PQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment, which was diagnosed based on investigators' experience. The evaluation includes 3 health conditions relevant to Protective Qi Deficiency (cold history, symptoms, and signs) but was neither standardized nor quantitative. PQi status was characterized as non-PQD (i.e., healthy condition, no PQD detected) or PQD (i.e., unhealthy condition). The change of the PQi status from baseline, indicating the treatment effect, was analyzed by categorical statistic.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of Generic Qi Score (GQS) Determined by a Standardized Assessment</measure>
    <time_frame>The change of GQS was obtained by deduction of GQS at each follow-up visit from the baseline (start date). The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
    <description>Generic Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 5 sets of criteria indicative of Generic Qi insufficiency (cold history, symptoms of PQD, symptoms of Lung Qi Deficiency, symptoms of Heart and Spleen Deficiency, and signs of GQD). Each set will be scored on a 1-10 scales, with 10 being the most healthy state. The sub-scores will be averaged to arrive at a final GQS. So this GQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the GQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of Generic Qi (GQi) Status Determined by Traditional TCM Assessment</measure>
    <time_frame>GQi was determined at the baseline (start date) and each follow-up visit. The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
    <description>GQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment,which was diagnosed based on investigators' experience and expertise. The evaluation was made through cold history, symptoms and signs but was neither standardized nor quantitative. GQi was characterized as Generic Qi Deficiency (GQD; unhealthy state) or non-GQD (healthy state). The change of the GQi status from baseline, indicating the treatment effect, was analyzed by rank-based statistic.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Protective Qi Insufficiency</condition>
  <arm_group>
    <arm_group_label>Proglucamune treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Proglucamune</intervention_name>
    <description>Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
    <arm_group_label>Proglucamune treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or females aged 18 to 65 years (inclusive) without regard to race or ethnic&#xD;
             background&#xD;
&#xD;
          2. Provide a signed Informed Consent prior to entry in the study.&#xD;
&#xD;
          3. Willing to follow all study instructions and consume the assigned investigational&#xD;
             product for 8 weeks.&#xD;
&#xD;
          4. Not currently taking a beta-glucan containing supplement or any other supplement that&#xD;
             might interfere with the study design.&#xD;
&#xD;
          5. Ability to swallow tablets and pills.&#xD;
&#xD;
          6. Diagnosed as having Qi deficiency based on the following criteria:&#xD;
&#xD;
               -  exhibit a history of susceptibility to cold* (* as defined in Traditional Chinese&#xD;
                  Medicine, TCM)&#xD;
&#xD;
               -  exhibit a shortness of breath&#xD;
&#xD;
               -  exhibit a lack of energy or excessive fatigue&#xD;
&#xD;
               -  susceptible to spontaneous perspiration&#xD;
&#xD;
               -  exhibit a corpulent tongue with or without white fur&#xD;
&#xD;
               -  unwillingness to speak&#xD;
&#xD;
               -  weak or powerless pulse&#xD;
&#xD;
               -  pale complexion&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Persons diagnosed by TCM as having medical conditions other than low Qi.&#xD;
&#xD;
          2. Significant acute or chronic illness or other medical conditions that will prevent or&#xD;
             interfere with giving an informed consent, or with participation in the study.&#xD;
&#xD;
          3. Persons with insulin-dependent and orally controlled diabetes will also be excluded&#xD;
             from the study.&#xD;
&#xD;
          4. Scheduling difficulties or lack of transportation that will prevent or interfere with&#xD;
             their ability to attend all of the necessary study visits.&#xD;
&#xD;
          5. Persons medically diagnosed with depression or anxiety disorders.&#xD;
&#xD;
          6. Persons with a history of alcohol abuse or other substance abuse within the previous 2&#xD;
             years.&#xD;
&#xD;
          7. Females who are attempting to become pregnant, pregnant, lactating or who have given&#xD;
             birth within 1 year.&#xD;
&#xD;
          8. Persons who have had a medical surgery in the past 4 weeks.&#xD;
&#xD;
          9. Persons currently enrolled in a clinical trial, or who have completed a clinical trial&#xD;
             within the last 4 weeks.&#xD;
&#xD;
         10. Allergies to mushrooms or other fungi.&#xD;
&#xD;
         11. Significant problems with constipation or diarrhea.&#xD;
&#xD;
         12. Persons exhibiting symptoms of cold* (*as defined by TCM) within the past 7 days.&#xD;
&#xD;
         13. A lifestyle or schedule incompatible with the study protocol.&#xD;
&#xD;
         14. Persons who are allergic to yeast products, have autoimmune disease/an immune&#xD;
             disorder, or take antidepressants, blood thinners (anticoagulants), or&#xD;
             immunosuppressant medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>participant eligibility is based on self-representation of gender identity.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ira Bernstein, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Family and Community Medicine, Humber River Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Elegant And Olive Health Clinic</name>
      <address>
        <city>Markham</city>
        <state>Ontario</state>
        <zip>L3R 5V6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Chan GC, Chan WK, Sze DM. The effects of beta-glucan on human immune and cancer cells. J Hematol Oncol. 2009 Jun 10;2:25. doi: 10.1186/1756-8722-2-25.</citation>
    <PMID>19515245</PMID>
  </reference>
  <reference>
    <citation>Bashir KMI, Choi JS. Clinical and Physiological Perspectives of beta-Glucans: The Past, Present, and Future. Int J Mol Sci. 2017 Sep 5;18(9):1906. doi: 10.3390/ijms18091906.</citation>
    <PMID>28872611</PMID>
  </reference>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <results_first_submitted>May 27, 2021</results_first_submitted>
  <results_first_submitted_qc>October 25, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">October 27, 2021</results_first_posted>
  <last_update_submitted>October 25, 2021</last_update_submitted>
  <last_update_submitted_qc>October 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Protective Qi</keyword>
  <keyword>Immunity</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 20, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/28/NCT03829228/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited from the great Toronto area in Canada through advertisement and referral from other TCM practitioners. The enrollment was conducted at the Elegant and Olive Health Clinic at Markham, Canada. Subjects that met the criteria for inclusion were enrolled. The first participants was enrolled on March 18th,2018 and the last participant was enrolled in April 8th, 2018.</recruitment_details>
      <pre_assignment_details>There was no wash-out or run-in period. All participants were assigned to received Proglucamune treatment. No participants were excluded before the start of treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Participants Received Proglucamune Treatment.</title>
          <description>Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Participants</title>
          <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.&#xD;
Proglucamune: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
          </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="47" lower_limit="18" upper_limit="64"/>
                  </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="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Medication</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Supplement</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Smoking</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Alcohol</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change of Protective Qi Score (PQS) Determined by a Standardized Assessment</title>
        <description>Protective Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 3 health conditions relevant to PQD (cold frequency, symptoms, and signs). Each condition will be scored on a 1-10 scale based on a set of standardized criteria. The sub-scores will be weighted to arrive at a final PQS. So this PQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the PQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
        <time_frame>The change of PQS was obtained by assessment of PQS at each follow-up visit from the baseline (start date). The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
        <population>Intent to treat population(all participants assigned to treatment). Last observation carried forward (LOCF) imputation method.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.&#xD;
Proglucamune: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Protective Qi Score (PQS) Determined by a Standardized Assessment</title>
          <description>Protective Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 3 health conditions relevant to PQD (cold frequency, symptoms, and signs). Each condition will be scored on a 1-10 scale based on a set of standardized criteria. The sub-scores will be weighted to arrive at a final PQS. So this PQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the PQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
          <population>Intent to treat population(all participants assigned to treatment). Last observation carried forward (LOCF) imputation method.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.3" spread="0.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.8" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.17" spread="0.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.27" spread="0.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.64" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The threshold for statistical significance was p=0.01</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.31</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.62</ci_lower_limit>
            <ci_upper_limit>2.01</ci_upper_limit>
            <estimate_desc>Treatment Difference= Visit5-Baseline</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change of Protective Qi (PQi) Status Determined by Traditional TCM Assessment</title>
        <description>PQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment, which was diagnosed based on investigators' experience. The evaluation includes 3 health conditions relevant to Protective Qi Deficiency (cold history, symptoms, and signs) but was neither standardized nor quantitative. PQi status was characterized as non-PQD (i.e., healthy condition, no PQD detected) or PQD (i.e., unhealthy condition). The change of the PQi status from baseline, indicating the treatment effect, was analyzed by categorical statistic.</description>
        <time_frame>PQi status was determined at the baseline (start date) and each follow-up visit. The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
        <population>Intent to treat population (all participants assigned to β-glucan treatment). Last observation carried forward (LOCF) imputation method.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.&#xD;
Proglucamune: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Protective Qi (PQi) Status Determined by Traditional TCM Assessment</title>
          <description>PQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment, which was diagnosed based on investigators' experience. The evaluation includes 3 health conditions relevant to Protective Qi Deficiency (cold history, symptoms, and signs) but was neither standardized nor quantitative. PQi status was characterized as non-PQD (i.e., healthy condition, no PQD detected) or PQD (i.e., unhealthy condition). The change of the PQi status from baseline, indicating the treatment effect, was analyzed by categorical statistic.</description>
          <population>Intent to treat population (all participants assigned to β-glucan treatment). Last observation carried forward (LOCF) imputation method.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <title>Non-PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit2</title>
              <category_list>
                <category>
                  <title>Non-PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit3</title>
              <category_list>
                <category>
                  <title>Non-PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit4</title>
              <category_list>
                <category>
                  <title>Non-PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit5</title>
              <category_list>
                <category>
                  <title>Non-PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>PQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The threshold for statistical significance was p=0.01</p_value_desc>
            <method>Regression, Logistic</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change of Generic Qi Score (GQS) Determined by a Standardized Assessment</title>
        <description>Generic Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 5 sets of criteria indicative of Generic Qi insufficiency (cold history, symptoms of PQD, symptoms of Lung Qi Deficiency, symptoms of Heart and Spleen Deficiency, and signs of GQD). Each set will be scored on a 1-10 scales, with 10 being the most healthy state. The sub-scores will be averaged to arrive at a final GQS. So this GQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the GQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
        <time_frame>The change of GQS was obtained by deduction of GQS at each follow-up visit from the baseline (start date). The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
        <population>Intent to treat population (all participants assigned to β-glucan treatment. Last observation carried forward (LOCF) imputation method.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.&#xD;
Proglucamune: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Generic Qi Score (GQS) Determined by a Standardized Assessment</title>
          <description>Generic Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 5 sets of criteria indicative of Generic Qi insufficiency (cold history, symptoms of PQD, symptoms of Lung Qi Deficiency, symptoms of Heart and Spleen Deficiency, and signs of GQD). Each set will be scored on a 1-10 scales, with 10 being the most healthy state. The sub-scores will be averaged to arrive at a final GQS. So this GQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the GQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
          <population>Intent to treat population (all participants assigned to β-glucan treatment. Last observation carried forward (LOCF) imputation method.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.34" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.76" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.16" spread="0.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.29" spread="0.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.65" spread="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The threshold for statistical significance was p=0.01</p_value_desc>
            <method>ANOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.31</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.64</ci_lower_limit>
            <ci_upper_limit>1.98</ci_upper_limit>
            <estimate_desc>Treatment difference=Visit5-Baseline</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change of Generic Qi (GQi) Status Determined by Traditional TCM Assessment</title>
        <description>GQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment,which was diagnosed based on investigators' experience and expertise. The evaluation was made through cold history, symptoms and signs but was neither standardized nor quantitative. GQi was characterized as Generic Qi Deficiency (GQD; unhealthy state) or non-GQD (healthy state). The change of the GQi status from baseline, indicating the treatment effect, was analyzed by rank-based statistic.</description>
        <time_frame>GQi was determined at the baseline (start date) and each follow-up visit. The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.</time_frame>
        <population>Intent to treat population (all participants assigned to β-glucan treatment). Last observation carried forward (LOCF) imputation method.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.&#xD;
Proglucamune: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Generic Qi (GQi) Status Determined by Traditional TCM Assessment</title>
          <description>GQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment,which was diagnosed based on investigators' experience and expertise. The evaluation was made through cold history, symptoms and signs but was neither standardized nor quantitative. GQi was characterized as Generic Qi Deficiency (GQD; unhealthy state) or non-GQD (healthy state). The change of the GQi status from baseline, indicating the treatment effect, was analyzed by rank-based statistic.</description>
          <population>Intent to treat population (all participants assigned to β-glucan treatment). Last observation carried forward (LOCF) imputation method.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <title>Non-GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit2</title>
              <category_list>
                <category>
                  <title>Non-GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit3</title>
              <category_list>
                <category>
                  <title>Non-GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit4</title>
              <category_list>
                <category>
                  <title>Non-GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Visit5</title>
              <category_list>
                <category>
                  <title>Non-GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>GQD</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>The threshold for statistical significant was p=0.01.</p_value_desc>
            <method>Regression, Logistic</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>8 weeks</time_frame>
      <desc>Our treatment tablets are supplement. All participants don't have allege in rhinitis, pollinosis( hay fever), or asthma.</desc>
      <group_list>
        <group group_id="E1">
          <title>All Participants</title>
          <description>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.&#xD;
Proglucamune: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS 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>
    <limitations_and_caveats>Study limitations: First, this was not a randomized, placebo-controlled trial, so the observed effect size likely was inflated by uncontrolled confounders. Second, most participants were receptive to the healing effects of TCM, which may have lead to an overestimate of treatment effect. Lastly, the clinical trial started when flu season had passed its peak. This may have decreased the chance of subjects catching the flu and thereby have led to improved PQi independent of Proglucamune treatment.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Junqiang Tian</name_or_title>
      <organization>USANA Health Science</organization>
      <phone>8019547462</phone>
      <email>jeremy.tian@usanainc.com</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/NCT03829228
org study id: 201875
nct id: NCT03829228
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
According to Traditional Chinese Medicine (TCM) principle, Protective Qi (PQi) is a one
      specific concept of Qi that provides the vital energy of the body. It works primarily on the
      body surface as a defensive barrier. In this context, PQi is analogous to anatomical barriers
      of the innate immune system located for example, at the skin surface and the mucosal surfaces
      of the respiratory and digestive tract. Individuals with PQi Insufficiency are predisposed to
      frequent cold and other symptoms caused by invasion of external pathogens ("Wai Xie" or
      "external evil" in TCM).

      ß-glucan is a polysaccharide that activates macrophage (Dectin-1) and neutrophil (CR3)
      receptors, and therefore enhances immune defense at digestive and respiratory mucosa.
      Clinical trials have shown its immune activity such as preventing upper respiratory tract
      infection (URTI) and Traveler's diarrhea. Notably, ß-glucan is a component of Ganoderma
      Luciderm (or Reishi / Lingzhi), one TCM ingredient well-known for improving Qi. Based on this
      connection, investigators hypothesized that ß-glucan is the active ingredient in Reishi that
      at least partially accounts for Reishi's activity on Qi.

      To test our hypothesis, investigators have conducted an uncontrolled pilot trial that
      investigated the effect of a commercially available, high ß-glucan containing product,
      Proglucamune®, on PQi status. Proglucamune contains ß-glucan from three different natural
      sources: Reishi mushroom, Shiitaki mushroom, and Bakers' yeast, each providing ß-glucan that
      differs slightly in their molecular structure. Through this pilot investigators sought to
      obtain an estimate of the effect size of Proglucamune on PQi that would allow us, via
      statistical methods, to estimate the necessary sample size for more definitive future trials.
Unlike mainstream Western medicine (WM), alternative medicines (AM) such as Traditional
      Chinese Medicine (TCM), emphasizes individually-differentiated therapies. As such, AM
      therapies are normally not tested in clinical studies that statistically demonstrate the
      efficacy at the populational level for applicable patients, and this makes it difficult to
      objectively evaluate and compare different therapies. The lack of clinical studies stands as
      a barrier for the advance of AMs as well as their engagement with WM. In fact, most
      researchers view AMs primarily as untapped sources of "active ingredients/compounds" for drug
      development, but disregard the rationales under which the therapies were developed. A
      "One-Way-Traffic" research paradigm is thus created wherein AM therapies are investigated for
      their efficacy by WM standards, whereas the vast potential of employing WM therapies for AM
      therapeutics is ignored. In light of this, investigators set up a novel strategy that bridges
      TCM and WM, i.e., testing a WM-based therapy by TCM standards through clinical
      trial/statistics- based method.

      Qi is a central concept of traditional Chinese medicine (TCM) and was first documented in the
      oldest TCM writings more than 2000 years ago. Generally speaking, Qi refers to the vital
      energy of the body and is derived from two primary sources: 1) inborn Qi (that may be
      construed as genetics), and 2) pectoral Qi (can be construed as metabolism). Moreover, Qi
      manifests itself in two forms: Nutritive Qi and Protective Qi, which can be understood to
      reflect an individual's nutritional state and immune health, respectively. Regarding the
      latter, protective Qi functions to defend the body from the invasion of external pathogens.
      TCM also emphasizes that Protective Qi works primarily on the body surface as a defensive
      barrier. In this context, Protective Qi is analogous to anatomical barriers of the innate
      immune system located for example, at the skin surface and the mucosal surfaces of the
      respiratory and digestive tract.

      TCM has developed a number of methods to strengthen the Qi. Prominent among these is the use
      of Reishi, either alone or in combination with other TCM remedies. The use of Reishi was
      described in detail in the first TCM pharmacopeia "Compendium of Materia Medica" published in
      year 1,600. Nonetheless, although Protective Qi is part of the general Qi, the specific
      effect of Reishi on Protective Qi is less documented. Anecdotal reports are available that
      claim significant improvement of Protective Qi with Reishi or Reishi-containing formulas
      within days. Notably, Western medicine has identified immune-boosting properties of Reishi,
      which may explain the Qi enhancing effects of this plant. Specifically, beta-glucan - a
      component of Reishi - has been shown to activate macrophage (large white blood cells in the
      immune system that destroy bacteria and other harmful substances), neutrophil (type of white
      blood cells that are important for protection against infections), and other immunocytes (a
      type of cells capable of producing an immune response), and may exhibit particular benefits
      among macrophage-rich organs such as the lung, liver and spleen. In fact, ß-glucans from
      sources other than Reishi, such as baker's yeast, are able to initiate the same immune
      response and clinical benefits.

      The overlap of TCM and western medicine concerning the beneficial effects of Reishi for its
      Qi enhancing and immune-modulating effects, respectively, has prompted us to investigate
      whether or not Reishi, in conjunction with other natural products used in TCM, can enhance an
      individual's Protective Qi. More specifically, the objective of the current protocol is to
      determine if a commercially available dietary supplement (Proglucamune®, USANA Health
      Sciences) containing powdered Reishi and Shitake mushrooms as well as baker's yeast extract,
      and which is comprised of 11% ß-glucans by weight, will improve Protective Qi in subjects
      diagnosed by practitioners of TCM as having low or insufficient Protective Qi. Specifically,
      in this a pilot study, investigators sought to obtain an estimate of the effect size of
      Proglucamune on PQi that would allow us, via statistical methods, to estimate the necessary
      sample size for more definitive future trials. The trial also aimed to provide information on
      individuals who are responsive to Proglucamune treatment (responder), and subsequently
      recruit targeted individuals for the follow-up trials.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Subjects with Protective Qi Insufficiency
primary purpose: Treatment
masking: None (Open Label)
masking description: Given the small sample size in this pilot study and the potential drop-out rate, we did not include a placebo group to control for the placebo effect. Nonetheless, we implemented a "deceptive" double-blinding design, i.e., all on-site care-providers and investigators and all participants were told that this study was placebo controlled, and that each participant had a 50/50 chance of receiving treatment or placebo. This masking helps decreasing the expectation bias from the participants that confound the study result.
measure: Change of Protective Qi Score (PQS) Determined by a Standardized Assessment
time frame: The change of PQS was obtained by assessment of PQS at each follow-up visit from the baseline (start date). The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.
description: Protective Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 3 health conditions relevant to PQD (cold frequency, symptoms, and signs). Each condition will be scored on a 1-10 scale based on a set of standardized criteria. The sub-scores will be weighted to arrive at a final PQS. So this PQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the PQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.
measure: Change of Protective Qi (PQi) Status Determined by Traditional TCM Assessment
time frame: PQi status was determined at the baseline (start date) and each follow-up visit. The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.
description: PQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment, which was diagnosed based on investigators' experience. The evaluation includes 3 health conditions relevant to Protective Qi Deficiency (cold history, symptoms, and signs) but was neither standardized nor quantitative. PQi status was characterized as non-PQD (i.e., healthy condition, no PQD detected) or PQD (i.e., unhealthy condition). The change of the PQi status from baseline, indicating the treatment effect, was analyzed by categorical statistic.
measure: Change of Generic Qi Score (GQS) Determined by a Standardized Assessment
time frame: The change of GQS was obtained by deduction of GQS at each follow-up visit from the baseline (start date). The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.
description: Generic Qi of each participant at baseline and each follow-up visit will be measured by an on-site investigator (licensed TCM practitioners) through a standardized quantitative assessment. The evaluation includes 5 sets of criteria indicative of Generic Qi insufficiency (cold history, symptoms of PQD, symptoms of Lung Qi Deficiency, symptoms of Heart and Spleen Deficiency, and signs of GQD). Each set will be scored on a 1-10 scales, with 10 being the most healthy state. The sub-scores will be averaged to arrive at a final GQS. So this GQS will be on a 1-10 scale, with 10 being the most healthy state. The change of the GQS from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.
measure: Change of Generic Qi (GQi) Status Determined by Traditional TCM Assessment
time frame: GQi was determined at the baseline (start date) and each follow-up visit. The follow-up visit was conducted every two weeks throughout the study, i.e., on the 14th, 28th, 42nd, and 56th day from the baseline.
description: GQi of each participant at baseline and each follow-up visit was measured by on-site investigators (licensed TCM practitioners) through the traditional TCM assessment,which was diagnosed based on investigators' experience and expertise. The evaluation was made through cold history, symptoms and signs but was neither standardized nor quantitative. GQi was characterized as Generic Qi Deficiency (GQD; unhealthy state) or non-GQD (healthy state). The change of the GQi status from baseline, indicating the treatment effect, was analyzed by rank-based statistic.
arm group label: Proglucamune treatment
arm group type: Experimental
description: Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks.
intervention type: Dietary Supplement
intervention name: Proglucamune
description: Following screening and enrollment, participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. Each Proglucamune tablet contained ~100 mg ß-glucan derived from Baker's Yeast extract (Saccharomyces cerevisiae, cell wall), Reishi mushroom powder (Ganoderma lucidum), and Shitake mushroom powder (Lentinula edodes).
arm group label: Proglucamune treatment
criteria: 
gender: All
gender based: Yes
gender description: participant eligibility is based on self-representation of gender identity.
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Ira Bernstein, MD
role: Principal Investigator
affiliation: Department of Family and Community Medicine, Humber River Hospital
facility: 
country: Canada
citation: Chan GC, Chan WK, Sze DM. The effects of beta-glucan on human immune and cancer cells. J Hematol Oncol. 2009 Jun 10;2:25. doi: 10.1186/1756-8722-2-25.
PMID: 19515245
citation: Bashir KMI, Choi JS. Clinical and Physiological Perspectives of beta-Glucans: The Past, Present, and Future. Int J Mol Sci. 2017 Sep 5;18(9):1906. doi: 10.3390/ijms18091906.
PMID: 28872611
responsible party type: Sponsor
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study limitations: First, this was not a randomized, placebo-controlled trial, so the observed effect size likely was inflated by uncontrolled confounders. Second, most participants were receptive to the healing effects of TCM, which may have lead to an overestimate of treatment effect. Lastly, the clinical trial started when flu season had passed its peak. This may have decreased the chance of subjects catching the flu and thereby have led to improved PQi independent of Proglucamune treatment.
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