Trial Information

A Phase 2 Study of the Reduction of Dietary Mycotoxin Exposure by ACCS100

This planned clinical trial is a comparative study to determine the safety and effectiveness
of ACCS100 capsules, the investigational product, vs. placebo in participants for the
reduction of dietary mycotoxin exposure. One measure of effectiveness will be the analysis
of the Bexar County participant's AFB1/FB1 metabolite levels in the blood and urine samples.
Additionally, this clinical trial will determine the adherence to the dosing schedule of
the participants; determine the prevalence of mycotoxin exposure in the screened population
of residence of Bexar County, Texas; and compare side-effects and adverse events between
ACCS100 and placebo in the participant population. These data will reveal the value of
mineral enterosorbent strategies for the improvement of public health and for the well-being
of humans at risk for dietary mycotoxin exposure and its consequences.

The proposed indication for ACCS100 is "for the reduction of dietary mycotoxin exposure in
humans."

ACCS100 is made from Hydrated Sodium Calcium Aluminosilicate (HSCAS), a substance generally
recognized as safe (GRAS) by the FDA and has previously been shown to have no significant
adverse effects when given as much as 4 grams per day to healthy study participants or
immuno-compromised cancer patients.

Rationale

Our preliminary studies suggest that ACCS100 contains very low levels of trace metals and
dioxins than are commonly found in smectite clays, and batch-to-batch QA/QC results for this
material are more consistent. We anticipate that ACCS100 can be used as a primary
intervention to bind both AFB1 and FB1 to decrease the external dose of toxins from the diet
and in turn reduce the incidence of hepatic cancer and disease in vulnerable communities.
Using multiple animal models, our laboratory has shown that NS clay is highly effective in
preventing the adverse effects of dietary mycotoxin. Also, Phase I and IIa clinical trials
in Texas and Ghana have confirmed that NS is safe for human consumption and significantly
reduces exposure to both AFB1 and FB1 (Wang et al., 2005; Afriyie-Gyawu et al., 2007, 2008;
Wang et al., 2008; Phillips et al., 2007; Jiang et al., 2008; Jolly et al., 2006; Robinson,
et al., 2009). The incidence of human HCC has been shown to be significantly elevated in
several zip code regions in Bexar County, Texas. Studies conducted by the Agency for Toxic
Substances and Disease Registry indicate that there are several zip code regions within
Bexar County, Texas where the incidence of liver cancer is significantly elevated (ATSDR,
2004). Notably, age-adjusted cancer incidence rates cited by the Texas Department of State
Health Services from 2002-2006 show that Hispanics in Bexar Co. have an increased HCC
incidence rate, 16.5 (15.0-18.0), compared to Hispanics in Texas, 10.9 (10.4-11.4); rates
are per 100,000, and confidence intervals are 95% for rates. Furthermore, the HCC incidence
rate for Bexar Co. Hispanics was considerably higher than all races in Bexar Co., 10.0
(9.2-10.8), and all races in Texas, 5.8 (5.7-6.0). Hispanic males in Bexar County (compared
to females) were shown to have the highest HCC incidence rate during this time period, at
27.1 (24.2-30.2) versus 8.4 (7.0-9.9). Chronic exposure to low levels of AFB1 and FB1
contaminated corn and peanuts, is a major risk factor for the development of HCC, and risk
is significantly increased when exposed individuals are infected with hepatitis virus. An
association between HCC incidence and hepatitis C virus (HCV) infection has been evident in
many developed countries including the U.S., Japan, Egypt, and numerous countries in Europe
(Seeff, 2004). Interestingly, records from the University of Texas M.D. Anderson Cancer
Center have shown that more than 50% of the HCC cases observed in Texas could be attributed
to HCV infection (Hassan, et al., 2002). The HCV prevalence in Texas has been reported to
vary from 1.25-2.63%, with higher concentrations in southern Texas and along the
Texas-Mexico border (Yalamanchili, et al., 2005). Armstrong et al. (2000) estimated that in
the future HCC incidence may rise in the U.S. due to the problem of chronic hepatitis C.
While prevention of HCV infection would play a major role in reducing the burden of HCC,
currently no vaccine is available for HCV. Thus, eliminating AFB1/FB1 exposure at an
individual level (in the most vulnerable individuals), may contribute to the overall
reduction of HCC risk and burden. In our recent pilot study, 184 volunteers from a primarily
Hispanic community within three zip codes in Bexar Co. (with a significantly elevated liver
cancer incidence rate) provided blood and urine samples for hepatitis screening and
biomarker analyses at the San Antonio Metropolitan Health District (SAMHD) Environmental
Health and Wellness Center (Figure 2). Of the participants, 7.1% were hepatitis C virus
positive, based on anti-HCV antibody measurement. To assess short-term AFB1 exposure,
urinary aflatoxin M1 (AFM1) levels were measured using high performance liquid
chromatography with fluorescence detection. AFM1 was detectable in 11.7% of urine samples,
with the average level at 223.85 ± 250.56 (range 1.89-935.49) pg/mg creatinine. Results from
a food frequency questionnaire showed that over 98% of participants reported that they ate
fresh corn, canned or frozen corn, corn tortillas, Mexican food, rice, peanut butter, corn
bread, and nuts at various frequencies. A large percentage of the population (44.8%)
consumed corn tortillas frequently (3-14 times per week), and the majority (57.6%) ate more
than 2 tortillas at each time of consumption. The detection of urinary AFM1 was
significantly associated with an increased consumption of tortillas (p = 0.009), peanuts (p
= 0.033) and rice (p = 0.037). Findings suggested that participants consuming high amounts
of foods prone to AFB1/FB1 contamination may potentially be exposed to these toxins at
significant levels. Importantly, strategies that reduce AFB1/FB1 exposure, especially in
individuals infected with hepatitis, may play an important role in the prevention of HCC in
at-risk communities in Texas. These preliminary studies provide the groundwork and proof of
concept for the proposed project. Feasible interventions and therapies to diminish human
exposure to AFB1/FB1 are imperative. In this proposal, studies will provide an innovative
strategy that will reduce dietary mycotoxin exposure. Our approach will utilize ACCS100 to
mitigate dietary exposures to AFB1 (a cancer initiator) and FB1 (a cancer promoter).