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Phase 2 Reduction of Dietary Mycotoxin Exposure by ACCS100" (RDMEACCS100)

This study has been completed.
Sponsor:
Collaborators:
Texas A&M University
University of Georgia
The University of Texas at San Antonio
Information provided by (Responsible Party):
Texas Enterosorbents Incorporated
ClinicalTrials.gov Identifier:
NCT01677195
First received: August 29, 2012
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Dietary Carcinogenesis
Drug: ACCS100
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: "Phase II, Reduction of Dietary Mycotoxin Exposure in Persons in Bexar County, Texas by Ingestion of ACCS100 Capsules Compared to Placebo."

Resource links provided by NLM:


Further study details as provided by Texas Enterosorbents Incorporated:

Primary Outcome Measures:
  • Reduction of dietary mycotoxin (Aflatoxin-AFB1 and Fumonisin-FB1) exposure in participants in Bexar County, Texas [ Time Frame: Two year study ] [ Designated as safety issue: No ]
    We hypothesize that ingesting ACCS100 prior to each meal (total of 1.5 or 3 g/day) will reduce the participant's exposure to AFB1 and FB1 as indicated by blood and urine levels of AFB1/FB1 metabolites. The ultimate purpose of this project will be to reveal the value of mineral enterosorbent strategies to reduce exposure to dietary mycotoxin risk factors for disease.


Secondary Outcome Measures:
  • Compare side-effects and adverse events between ACCS100 and placebo in the participant population [ Time Frame: 2 Year study ] [ Designated as safety issue: Yes ]
    The raw material from which ACCS100 is produced is generally recognized as safe (GRAS) by the FDA, is an approved food and feed additive, and is considered safe at up to 40 grams of a 2 kg/day diet. The maximum dose of ACCS100 for this study is 3.0 grams per day or less than one-tenth of the maximum level in food permitted by the FDA.


Other Outcome Measures:
  • • Determine the prevalence of mycotoxin exposure in the screened population of residence of Bexar County, Texas [ Time Frame: 2 Year Study ] [ Designated as safety issue: Yes ]
    Approximately 800 potential participants will be screened for blood or urine levels of aflatoxin and fumonisin. The results of this epidemiological and incidence survey is a part of the information that will be reported.


Enrollment: 232
Study Start Date: September 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ACCS100 High Dose
Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.
Drug: ACCS100
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.
Other Names:
  • HSCAS
  • UPSN
  • NS
Active Comparator: ACCS100 Low Dose
Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.
Drug: ACCS100
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.
Other Names:
  • HSCAS
  • UPSN
  • NS
Placebo Comparator: Placebo
Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.
Drug: Placebo
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 Name: Calcium Carbonate

  Hide Detailed Description

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).

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

3.1 Participant Inclusion Criteria 3.1.1 Detectable blood AFB1-albumin adduct levels (limit of detection=0.01 pmol/mg albumin) 3.1.2 18 -85 years 3.1.3 Ability to take oral capsules 3.1.4 Negative urine pregnancy test for women of childbearing age 3.1.5 Must have the ability to understand and the willingness to provide a written informed consent to participate in the study

Exclusion Criteria:

3.2 Participant Exclusion Criteria 3.2.1 History of known allergy to silicates 3.2.2 Pregnancy or lactation 3.2.3 History of significant neurological or psychiatric disorders that would impede giving consent, treatment, or follow up 3.2.4 Any serious systemic disorders incompatible with the study 3.2.5 History of chronic disease (ie heart disease, renal disease). A participant may have a diagnosis of and be managed for diabetes) Any recent diagnosis of cancer.

3.2.6 Participation in any other clinical study where the participant is actively taking an investigational medication within the last 30 days

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01677195

Locations
United States, Texas
University of Texas Health Science Center Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Texas Enterosorbents Incorporated
Texas A&M University
University of Georgia
The University of Texas at San Antonio
Investigators
Principal Investigator: Bradley H Pollock, MPH, Ph.D. University of Texas Health Science Center San Antonio Texas
  More Information

Publications:
Responsible Party: Texas Enterosorbents Incorporated
ClinicalTrials.gov Identifier: NCT01677195     History of Changes
Other Study ID Numbers: TxESI 12-001
Study First Received: August 29, 2012
Last Updated: August 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Texas Enterosorbents Incorporated:
Mycotoxins
Aflatoxin
Fumonisin
Aflatoxicosis
Dietary
Cancer

Additional relevant MeSH terms:
Carcinogenesis
Neoplasms
Neoplastic Processes
Pathologic Processes
Calcium Carbonate
Antacids
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014