<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/NCT03782974</url>
  </required_header>
  <id_info>
    <org_study_id>201878</org_study_id>
    <nct_id>NCT03782974</nct_id>
  </id_info>
  <brief_title>A Follow-up Trial of Proglucamune® in the Treatment of Protective Qi Insufficiency, a TCM Condition</brief_title>
  <official_title>A Randomized, Placebo-controlled, Triple-blinded 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>
      This is a follow-up Phase II study of a previously complete pilot trial (Protocol ID: 201875)&#xD;
      with the same goal: evaluating the activity of Proglucamune on Protective Qi (PQi)&#xD;
      Insufficiency.&#xD;
&#xD;
      According to Traditional Chinese Medicine (TCM) principle, Protective Qi is a one specific&#xD;
      concept of Qi that provides the vital energy of the body. It works primarily on the body&#xD;
      surface as a defensive barrier. In this context, Protective Qi is analogous to anatomical&#xD;
      barriers of the innate immune system located for example, at the skin surface and the mucosal&#xD;
      surfaces of the respiratory and digestive tract. Individuals with PQi Insufficiency are&#xD;
      predisposed to frequent cold and other symptoms caused by invasion of external pathogens&#xD;
      (&quot;Wai Xie&quot; or &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. The data obtained demonstrated a statistically&#xD;
      significant effect of Proglucamune on improving PQi in individuals with PQi Insufficiency.&#xD;
      The current study is aimed to further determine this effect in a more stringent&#xD;
      (placebo-controlled, randomized, and triple-blinded) way.&#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 in TCM and was first documented in the oldest TCM writings more than&#xD;
      2000 years ago. Generally speaking, Qi refers to the vital energy of the body and is derived&#xD;
      from two primary sources: 1) inborn Qi (that may be construed as genetics), and 2) pectoral&#xD;
      Qi (can be construed as metabolism). Moreover, Qi manifests itself in two forms: Nutritive Qi&#xD;
      and Protective Qi (PQi), which can be understood to reflect an individual's nutritional state&#xD;
      and immune health, respectively. Regarding the latter, protective Qi functions to defend the&#xD;
      body from the invasion of external pathogens. TCM also emphasizes that Protective Qi works&#xD;
      primarily on the body surface as a defensive barrier. In this context, Protective Qi is&#xD;
      analogous to anatomical barriers of the innate immune system located for example, at the skin&#xD;
      surface and the mucosal surfaces of the 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 pharmacopedia &quot;Compendium of Materia Medica&quot; published&#xD;
      in year 1,600. Nonetheless, although PQi is part of the general Qi, the specific effect of&#xD;
      Reishi on Protective Qi is less documented. Anecdotal reports are available that claim&#xD;
      significant improvement of Protective Qi with Reishi or Reishi- containing formulas within&#xD;
      days. Notably, WM has identified immune-boosting properties of Reishi, which may explain the&#xD;
      Qi enhancing effects of this plant. Specifically, beta-glucan - a component of Reishi - has&#xD;
      been shown to activate macrophage (large white blood cells in the immune system that destroy&#xD;
      bacteria and other harmful substances), neutrophil (a type of white blood cells that are&#xD;
      important for protection against infections), and other immunocytes (cells capable of&#xD;
      producing an immune response), and may exhibit particular benefits among macrophage-rich&#xD;
      organs such as the lung, liver and spleen. In fact, ß-glucans from sources other than Reishi,&#xD;
      such as baker's yeast, are able to initiate the same immune 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. A previous Pilot trial has been conducted that aimed to determine&#xD;
      if a commercially available dietary supplement (Proglucamune®, USANA Health Sciences)&#xD;
      containing powdered Reishi and Shitake mushrooms as well as baker's yeast extract, and which&#xD;
      is comprised of 11% ß-glucans by weight, would improve Protective Qi in subjects diagnosed by&#xD;
      practitioners of TCM as having low or insufficient Protective Qi. The data obtained&#xD;
      demonstrated a statistically significant effect of Proglucamune on improving PQi. Based on&#xD;
      the effect size and variability, investigators have arrived, via statistical methods, at the&#xD;
      necessary sample size for a more definitive (placebo-controlled, randomized, and&#xD;
      triple-blinded) trial.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">January 6, 2019</start_date>
  <completion_date type="Anticipated">June 6, 2019</completion_date>
  <primary_completion_date type="Anticipated">June 6, 2019</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>Parallel Assignment</intervention_model>
    <intervention_model_description>Individuals with Protective Qi Insufficiency</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>All participants, on-site care-providers and investigators, and the outcome assessors will be informed that this study is placebo controlled, and that each participant has a 50/50 chance of receiving treatment or placebo. The test material will include treatment and placebo, both coated by the same coating. The code will be kept by the sponsor and disclosed after the analyses are completed.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Protective Qi improvement</measure>
    <time_frame>The participants will be followed every two weeks for a total of 12 weeks.</time_frame>
    <description>The Protective Qi status of participants at baseline and each follow-up visit will be assessed by on-site investigators (licensed TCM practitioners). Each health condition relevant to protective Qi insufficiency (i.e., cold history, symptoms, and signs) will be scored on a 1-10 or 1-5 scale (with higher number indicating more severe insufficiency) based on a set of standardized and specified criteria (see uploaded Study Protocol for specifics). The sub-scores are then weighted (cold history 25%, symptoms 33.3%, signs: 41.7%) to arrive at a final Protective Qi Insufficiency Index. This index is on a 1-5 scale, with 5 being the most severe insufficiency. The change of the score from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Generic Qi improvement</measure>
    <time_frame>The participants will be followed every two weeks for a total of 12 weeks.</time_frame>
    <description>The generic Qi status of participants at baseline and each follow-up visit will be assessed by on-site investigators (licensed TCM practitioners). The assessment consists of two parts of health conditions relevant to generic Qi insufficiency (symptoms and signs). Each part will be scored on a 1-5 scale (with 5 being the most severe insufficiency) based on a set of standardized and specified criteria (See uploaded Study Protocol). The sub-scores are then weighted (symptoms 40% and signs 60%) to arrive at a combined generic Qi Insufficiency Index. This index is on a 1-5 scale, with 5 being the most severe insufficiency. The change of the score from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global Health</measure>
    <time_frame>The participants will be followed every two weeks for a total of 12 weeks.</time_frame>
    <description>The participants' Global Health will be assessed using the established PROMIS® Scale v1.2 (See the link http://www.healthmeasures.net/explore-measurement-systems/promis or the Citation below for detail). This questionnaire consists of 10 global-health related questions. The answer for nine of ten questions are graded on 1-5 scale (with 5 being the best), and one question is graded on 1 to 10 scale (with 10 being the worst grade). The sub-scores are used to obtain a final combined score of Global Health using a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional Impact</measure>
    <time_frame>The participants will be followed every two weeks for a total of 12 weeks.</time_frame>
    <description>The participants' Emotional status will be assessed using the ASCO-Me® v2.0 Emotional Impact (Short Form). This questionnaire-based survey was established based on a Sickle-cell patient population (Please see the link http://www.ascq-me.org/Science or the citation below for detail). This questionnaire consists of 5 emotional-status related questions. The answer for each of the questions are graded on five levels from best to worst. A combined score is generated using a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Saliva sIgA</measure>
    <time_frame>The participants will be followed every 6 weeks during 12 week trial.</time_frame>
    <description>The effect of Proglucamune on the participants' immunity will be assessed by the change of saliva secretary IgA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Emotional and Behavioral Dyscontrol - Short Form</measure>
    <time_frame>The participants will be followed every two weeks for a total of 12 weeks.</time_frame>
    <description>Neuro-QoL (Quality of Life in Neurological Disorders) is a measurement system that evaluates and monitors the physical, mental, and social effects experienced by adults and children living with neurological conditions. Please see the link (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol) for details. This questionnaire consists of 8 questions related to emotional and behavioral control. The answers for each of the questions are graded on five levels from best to worst. A combined score is generated using a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">130</enrollment>
  <condition>Protective Qi Insufficiency (a Condition Term From TCM)</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 (containing 200mg of beta glucan) for a total duration of 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants were treated with 2 tablets of placebo per day (contain no beta glucan) for a total duration of 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>beta glucan</intervention_name>
    <description>Following screening and enrollment, participants will be treated with 2 tablets (Proglucamune or placebo) 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>Placebo</arm_group_label>
    <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 12 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. Exhibit an PQi Insufficiency score &gt; 2 (See Primary Outcome Measure)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  1. Persons diagnosed by TCM as having medical conditions other than low Qi. 2.&#xD;
             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. Scheduling difficulties or lack of transportation that will prevent or interfere&#xD;
             with their ability to attend all of the necessary study visits.&#xD;
&#xD;
             4. Persons medically diagnosed with depression or anxiety disorders. 5. Persons with a&#xD;
             history of alcohol abuse or other substance abuse within the previous 2 years.&#xD;
&#xD;
             6. Females who are attempting to become pregnant, pregnant, lactating or who have&#xD;
             given birth within 1 year.&#xD;
&#xD;
             7. Persons who have had a medical surgery in the past 4 weeks or have scheduled a&#xD;
             surgery during the study period.&#xD;
&#xD;
             8. Persons currently enrolled in a clinical trial, or who have completed a clinical&#xD;
             trial within the last 4 weeks.&#xD;
&#xD;
             9. Allergies to mushrooms or other fungi. 10. Significant problems with constipation&#xD;
             or diarrhea. 11. A lifestyle or schedule incompatible with the study protocol. 12.&#xD;
             Persons who are allergic to yeast products, have autoimmune disease/an immune&#xD;
             disorder, or take antidepressants, blood thinners (anticoagulants, acetylsalicylic&#xD;
             acid), or 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>
  <overall_contact>
    <last_name>Jianpin Shi</last_name>
    <phone>416-707-7552</phone>
    <email>shi.jennyjp@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jeremy Tian, PhD</last_name>
    <phone>8019647462</phone>
    <email>jeremy.tian@us.usana.com</email>
  </overall_contact_backup>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>John Wu, MD</last_name>
      <phone>‭416-456-7318‬</phone>
      <email>johnwu43@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.healthmeasures.net/explore-measurement-systems/promis</url>
    <description>description for Global Health Questionnaire (PROMIS® Scale v1.2.)</description>
  </link>
  <link>
    <url>http://www.ascq-me.org/Science</url>
    <description>description for Emotional Impact Questionnaire: ASCO-Me® v2.0 Emotional Impact (Short Form)</description>
  </link>
  <link>
    <url>http://www.healthmeasures.net/explore-measurement-systems/neuro-qol</url>
    <description>description for Emotional &amp; Behavioral Dyscontrol Questionnaire (Neuro-QoL)</description>
  </link>
  <reference>
    <citation>Keller SD, Yang M, Treadwell MJ, Werner EM, Hassell KL. Patient reports of health outcome for adults living with sickle cell disease: development and testing of the ASCQ-Me item banks. Health Qual Life Outcomes. 2014 Aug 22;12:125. doi: 10.1186/s12955-014-0125-0.</citation>
    <PMID>25146160</PMID>
  </reference>
  <reference>
    <citation>Hays RD, Spritzer KL, Thompson WW, Cella D. U.S. General Population Estimate for &quot;Excellent&quot; to &quot;Poor&quot; Self-Rated Health Item. J Gen Intern Med. 2015 Oct;30(10):1511-6. doi: 10.1007/s11606-015-3290-x. Epub 2015 Apr 2.</citation>
    <PMID>25832617</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>December 18, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>January 28, 2019</last_update_submitted>
  <last_update_submitted_qc>January 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Protective Qi</keyword>
  <keyword>Immunity</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/74/NCT03782974/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>June 24, 2022</submitted>
    <returned>April 27, 2023</returned>
    <submitted>May 9, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03782974
org study id: 201878
nct id: NCT03782974
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a follow-up Phase II study of a previously complete pilot trial (Protocol ID: 201875)
      with the same goal: evaluating the activity of Proglucamune on Protective Qi (PQi)
      Insufficiency.

      According to Traditional Chinese Medicine (TCM) principle, Protective Qi 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, 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. 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. The data obtained demonstrated a statistically
      significant effect of Proglucamune on improving PQi in individuals with PQi Insufficiency.
      The current study is aimed to further determine this effect in a more stringent
      (placebo-controlled, randomized, and triple-blinded) way.
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 in 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 (PQi), 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 pharmacopedia "Compendium of Materia Medica" published
      in year 1,600. Nonetheless, although PQi 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, WM 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 (a type of white blood cells that are
      important for protection against infections), and other immunocytes (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. A previous Pilot trial has been conducted that aimed 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, would improve Protective Qi in subjects diagnosed by
      practitioners of TCM as having low or insufficient Protective Qi. The data obtained
      demonstrated a statistically significant effect of Proglucamune on improving PQi. Based on
      the effect size and variability, investigators have arrived, via statistical methods, at the
      necessary sample size for a more definitive (placebo-controlled, randomized, and
      triple-blinded) trial.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Individuals with Protective Qi Insufficiency
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: All participants, on-site care-providers and investigators, and the outcome assessors will be informed that this study is placebo controlled, and that each participant has a 50/50 chance of receiving treatment or placebo. The test material will include treatment and placebo, both coated by the same coating. The code will be kept by the sponsor and disclosed after the analyses are completed.
measure: Protective Qi improvement
time frame: The participants will be followed every two weeks for a total of 12 weeks.
description: The Protective Qi status of participants at baseline and each follow-up visit will be assessed by on-site investigators (licensed TCM practitioners). Each health condition relevant to protective Qi insufficiency (i.e., cold history, symptoms, and signs) will be scored on a 1-10 or 1-5 scale (with higher number indicating more severe insufficiency) based on a set of standardized and specified criteria (see uploaded Study Protocol for specifics). The sub-scores are then weighted (cold history 25%, symptoms 33.3%, signs: 41.7%) to arrive at a final Protective Qi Insufficiency Index. This index is on a 1-5 scale, with 5 being the most severe insufficiency. The change of the score from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.
measure: Generic Qi improvement
time frame: The participants will be followed every two weeks for a total of 12 weeks.
description: The generic Qi status of participants at baseline and each follow-up visit will be assessed by on-site investigators (licensed TCM practitioners). The assessment consists of two parts of health conditions relevant to generic Qi insufficiency (symptoms and signs). Each part will be scored on a 1-5 scale (with 5 being the most severe insufficiency) based on a set of standardized and specified criteria (See uploaded Study Protocol). The sub-scores are then weighted (symptoms 40% and signs 60%) to arrive at a combined generic Qi Insufficiency Index. This index is on a 1-5 scale, with 5 being the most severe insufficiency. The change of the score from baseline, indicating the treatment effect, will be calculated and analyzed by statistical means.
measure: Global Health
time frame: The participants will be followed every two weeks for a total of 12 weeks.
description: The participants' Global Health will be assessed using the established PROMIS® Scale v1.2 (See the link http://www.healthmeasures.net/explore-measurement-systems/promis or the Citation below for detail). This questionnaire consists of 10 global-health related questions. The answer for nine of ten questions are graded on 1-5 scale (with 5 being the best), and one question is graded on 1 to 10 scale (with 10 being the worst grade). The sub-scores are used to obtain a final combined score of Global Health using a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
measure: Emotional Impact
time frame: The participants will be followed every two weeks for a total of 12 weeks.
description: The participants' Emotional status will be assessed using the ASCO-Me® v2.0 Emotional Impact (Short Form). This questionnaire-based survey was established based on a Sickle-cell patient population (Please see the link http://www.ascq-me.org/Science or the citation below for detail). This questionnaire consists of 5 emotional-status related questions. The answer for each of the questions are graded on five levels from best to worst. A combined score is generated using a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
measure: Saliva sIgA
time frame: The participants will be followed every 6 weeks during 12 week trial.
description: The effect of Proglucamune on the participants' immunity will be assessed by the change of saliva secretary IgA.
measure: Emotional and Behavioral Dyscontrol - Short Form
time frame: The participants will be followed every two weeks for a total of 12 weeks.
description: Neuro-QoL (Quality of Life in Neurological Disorders) is a measurement system that evaluates and monitors the physical, mental, and social effects experienced by adults and children living with neurological conditions. Please see the link (http://www.healthmeasures.net/explore-measurement-systems/neuro-qol) for details. This questionnaire consists of 8 questions related to emotional and behavioral control. The answers for each of the questions are graded on five levels from best to worst. A combined score is generated using a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.
arm group label: Proglucamune treatment
arm group type: Experimental
description: Participants were treated with 2 tablets of Proglucamune per day (containing 200mg of beta glucan) for a total duration of 8 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants were treated with 2 tablets of placebo per day (contain no beta glucan) for a total duration of 8 weeks.
intervention type: Dietary Supplement
intervention name: beta glucan
description: Following screening and enrollment, participants will be treated with 2 tablets (Proglucamune or placebo) 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: Placebo
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
last name: Jianpin Shi
phone: 416-707-7552
email: shi.jennyjp@gmail.com
last name: Jeremy Tian, PhD
phone: 8019647462
email: jeremy.tian@us.usana.com
facility: 
status: Recruiting
contact: 
country: Canada
url: http://www.healthmeasures.net/explore-measurement-systems/promis
description: description for Global Health Questionnaire (PROMIS® Scale v1.2.)
url: http://www.ascq-me.org/Science
description: description for Emotional Impact Questionnaire: ASCO-Me® v2.0 Emotional Impact (Short Form)
url: http://www.healthmeasures.net/explore-measurement-systems/neuro-qol
description: description for Emotional & Behavioral Dyscontrol Questionnaire (Neuro-QoL)
citation: Keller SD, Yang M, Treadwell MJ, Werner EM, Hassell KL. Patient reports of health outcome for adults living with sickle cell disease: development and testing of the ASCQ-Me item banks. Health Qual Life Outcomes. 2014 Aug 22;12:125. doi: 10.1186/s12955-014-0125-0.
PMID: 25146160
citation: Hays RD, Spritzer KL, Thompson WW, Cella D. U.S. General Population Estimate for "Excellent" to "Poor" Self-Rated Health Item. J Gen Intern Med. 2015 Oct;30(10):1511-6. doi: 10.1007/s11606-015-3290-x. Epub 2015 Apr 2.
PMID: 25832617
responsible party type: Sponsor
mesh term: Disease
sharing ipd: Undecided
provided document: 
submitted: June 24, 2022
returned: April 27, 2023
submitted: May 9, 2023