Phase 2 Reduction of Dietary Mycotoxin Exposure by ACCS100"
Condition: Dietary Carcinogenesis
MeSH terms: Carcinogenesis
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary purpose of the study is to evaluate the effectiveness of a naturally occurring
      clay substance (ACCS100) in reducing harmful effects of aflatoxin exposure (a carcinogen) and
      fumonisin (a cancer promoter). This clay substance contains of a variety of minerals
      including calcium, sodium, potassium, and magnesium. UPSN and similar aluminosilicate
      minerals have been regularly used as dietary supplements by humans and animals, and the
      safety of this naturally occurring clay substance has been tested in clinical trials. The FDA
      treats such minerals or nutritional supplements as a drug when tested for potential of
      lessening the likelihood of disease (i.e., potential for mitigating disease).

      This study involves the use of an investigational drug called Hydrated Sodium Calcium
      Aluminosilicate (ACCS100). "Investigational" means that the "drug" has not yet been approved
      by the U.S. Food & Drug Administration (FDA) for reducing harmful effects mycotoxin exposure
      in humans.
    

Detailed description: 
      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).
    

Intervention name(s): ACCS100; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): ACCS100 is not absorbed. The dose is estimated based on the volume of the gastrointestinal tract. We estimate that the average human intestinal tract has a volume of approximately 4 liters. In the high dose group, the effective concentration in the gut is 0.75 milligrams per milliliter. In the low dose, the effective concentration in the gut is 0.375 milligrams per milliliter. The test article is made by filling gelatin capsules with 500 milligrams of ACCS100. There are no excipients used in the manufacturing process of the test article.; Placebo is calcium carbonate, USP. This calcium mineral does not absorb mycotoxins, specifically aflatoxin and fumonisin. This mineral has approximately the same physical appearance as active test article.
Other intervention name(s): HSCAS; UPSN; NS; Calcium Carbonate
Intervention MeSH terms: Calcium Carbonate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Mycotoxins; Aflatoxin; Fumonisin; Aflatoxicosis; Dietary; Cancer