A Follow-up Trial of Proglucamune® in the Treatment of Protective Qi Deficiency, a TCM Condition

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 Lucidum (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.

Eligibility Criteria:
Inclusion Criteria:

1. Male or females aged 18 to 65 years (inclusive) without regard to race or ethnic background
2. Provide a signed Informed Consent prior to entry in the study.
3. Willing to follow all study instructions and consume the assigned investigational product for 12 weeks.
4. Not currently taking a beta-glucan containing supplement or any other supplement that might interfere with the study design.
5. Ability to swallow tablets and pills.
6. Exhibit an PQi Insufficiency score \> 2 (See Primary Outcome Measure)

Exclusion Criteria:

1. Persons diagnosed by TCM as having medical conditions other than low Qi.
2. 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.
3. Scheduling difficulties or lack of transportation that will prevent or interfere with their ability to attend all of the necessary study visits.
4. Persons medically diagnosed with depression or anxiety disorders.
5. Persons with a history of alcohol abuse or other substance abuse within the previous 2 years.
6. Females who are attempting to become pregnant, pregnant, lactating or who have given birth within 1 year.
7. Persons who have had a medical surgery in the past 4 weeks or have scheduled a surgery during the study period.
8. Persons currently enrolled in a clinical trial, or who have completed a clinical trial within the last 4 weeks.
9. Allergies to mushrooms or other fungi.
10. Significant problems with constipation or diarrhea.
11. A lifestyle or schedule incompatible with the study protocol.
12. Persons who are allergic to yeast products, have autoimmune disease/an immune disorder, or take antidepressants, blood thinners (anticoagulants, acetylsalicylic acid), or immunosuppressant medication