An Evaluation of Proglucamune in the Treatment of Protective Qi Insufficiency

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Evaluation of Proglucamune in the Treatment of Protective Qi

Conditions
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Protective Qi Insufficiency

Intervention / Treatment
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* Dietary Supplement: Proglucamune


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or females aged 18 to 65 years (inclusive) without regard to race or ethnic background Provide a signed Informed Consent prior to entry in the study. Willing to follow all study instructions and consume the assigned investigational product for 8 weeks. Not currently taking a beta-glucan containing supplement or any other supplement that might interfere with the study design. Ability to swallow tablets and pills. Diagnosed as having Qi deficiency based on the following criteria: exhibit a history of susceptibility to cold* (* as defined in Traditional Chinese Medicine, TCM) exhibit a shortness of breath exhibit a lack of energy or excessive fatigue susceptible to spontaneous perspiration exhibit a corpulent tongue with or without white fur unwillingness to speak weak or powerless pulse pale complexion Exclusion Criteria: Persons diagnosed by TCM as having medical conditions other than low Qi. Significant acute or chronic illness or other medical conditions that will prevent or interfere with giving an informed consent, or with participation in the study. Persons with insulin-dependent and orally controlled diabetes will also be excluded from the study. Scheduling difficulties or lack of transportation that will prevent or interfere with their ability to attend all of the necessary study visits. Persons medically diagnosed with depression or anxiety disorders. Persons with a history of alcohol abuse or other substance abuse within the previous 2 years. Females who are attempting to become pregnant, pregnant, lactating or who have given birth within 1 year. Persons who have had a medical surgery in the past 4 weeks. Persons currently enrolled in a clinical trial, or who have completed a clinical trial within the last 4 weeks. Allergies to mushrooms or other fungi. Significant problems with constipation or diarrhea. Persons exhibiting symptoms of cold* (*as defined by TCM) within the past 7 days. A lifestyle or schedule incompatible with the study protocol. Persons who are allergic to yeast products, have autoimmune disease/an immune disorder, or take antidepressants, blood thinners (anticoagulants), or immunosuppressant medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects with Protective Qi Insufficiency
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Proglucamune treatment<br>Participants were treated with 2 tablets of Proglucamune per day for a total duration of 8 weeks. | Dietary Supplement: Proglucamune<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Protective Qi Score (PQS) Determined by a Standardized Assessment | 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. | 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. | 
| Change of Protective Qi (PQi) Status Determined by Traditional TCM Assessment | 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. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Generic Qi Score (GQS) Determined by a Standardized Assessment | 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. | 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. | 
| Change of Generic Qi (GQi) Status Determined by Traditional TCM Assessment | 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. | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Protective Qi, Immunity