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

Primary Purpose

Dietary Carcinogenesis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ACCS100
Placebo
Sponsored by
Texas Enterosorbents Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dietary Carcinogenesis focused on measuring Mycotoxins, Aflatoxin, Fumonisin, Aflatoxicosis, Dietary, Cancer

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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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Sites / Locations

  • University of Texas Health Science Center Cancer Therapy and Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Placebo Comparator

Arm Label

ACCS100 High Dose

ACCS100 Low Dose

Placebo

Arm Description

Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.

Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.

Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.

Outcomes

Primary Outcome Measures

AFB1-lysine Adduct (pg/mg) Overtime
After randomization, participants provided serum samples at baseline, weeks 4, 12, and 16. Week 16 represents one month off treatment.

Secondary Outcome Measures

Full Information

First Posted
August 29, 2012
Last Updated
March 20, 2016
Sponsor
Texas Enterosorbents Incorporated
Collaborators
Texas A&M University, University of Georgia, The University of Texas at San Antonio
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1. Study Identification

Unique Protocol Identification Number
NCT01677195
Brief Title
Phase 2 Reduction of Dietary Mycotoxin Exposure by ACCS100"
Acronym
RDMEACCS100
Official Title
"Phase II, Reduction of Dietary Mycotoxin Exposure in Persons in Bexar County, Texas by Ingestion of ACCS100 Capsules Compared to Placebo."
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Texas Enterosorbents Incorporated
Collaborators
Texas A&M University, University of Georgia, The University of Texas at San Antonio

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dietary Carcinogenesis
Keywords
Mycotoxins, Aflatoxin, Fumonisin, Aflatoxicosis, Dietary, Cancer

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
234 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ACCS100 High Dose
Arm Type
Active Comparator
Arm Description
Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.
Arm Title
ACCS100 Low Dose
Arm Type
Active Comparator
Arm Description
Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.
Intervention Type
Drug
Intervention Name(s)
ACCS100
Other Intervention Name(s)
HSCAS, UPSN, NS
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Calcium Carbonate
Intervention Description
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.
Primary Outcome Measure Information:
Title
AFB1-lysine Adduct (pg/mg) Overtime
Description
After randomization, participants provided serum samples at baseline, weeks 4, 12, and 16. Week 16 represents one month off treatment.
Time Frame
3 months on intervention (weeks 0-12); 1 month off intervention (week 16)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bradley H Pollock, MPH, Ph.D.
Organizational Affiliation
University of Texas Health Science Center San Antonio Texas
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Texas Health Science Center Cancer Therapy and Research Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Study submitted for publication in Tier 1 Toxicology Journal
Citations:
PubMed Identifier
22324939
Citation
Robinson A, Johnson NM, Strey A, Taylor JF, Marroquin-Cardona A, Mitchell NJ, Afriyie-Gyawu E, Ankrah NA, Williams JH, Wang JS, Jolly PE, Nachman RJ, Phillips TD. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B(1) exposure in rats and humans. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2012;29(5):809-18. doi: 10.1080/19440049.2011.651628. Epub 2012 Feb 10.
Results Reference
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PubMed Identifier
20870273
Citation
Johnson NM, Qian G, Xu L, Tietze D, Marroquin-Cardona A, Robinson A, Rodriguez M, Kaufman L, Cunningham K, Wittmer J, Guerra F, Donnelly KC, Williams JH, Wang JS, Phillips TD. Aflatoxin and PAH exposure biomarkers in a U.S. population with a high incidence of hepatocellular carcinoma. Sci Total Environ. 2010 Nov 1;408(23):6027-31. doi: 10.1016/j.scitotenv.2010.09.005. Epub 2010 Sep 25.
Results Reference
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Phase 2 Reduction of Dietary Mycotoxin Exposure by ACCS100"

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