<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01677195</url>
  </required_header>
  <id_info>
    <org_study_id>TxESI 12-001</org_study_id>
    <nct_id>NCT01677195</nct_id>
  </id_info>
  <brief_title>Phase 2 Reduction of Dietary Mycotoxin Exposure by ACCS100&quot;</brief_title>
  <acronym>RDMEACCS100</acronym>
  <official_title>&quot;Phase II, Reduction of Dietary Mycotoxin Exposure in Persons in Bexar County, Texas by Ingestion of ACCS100 Capsules Compared to Placebo.&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Enterosorbents Incorporated</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Texas A&amp;M University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Georgia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The University of Texas at San Antonio</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Texas Enterosorbents Incorporated</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of the study is to evaluate the effectiveness of a naturally occurring&#xD;
      clay substance (ACCS100) in reducing harmful effects of aflatoxin exposure (a carcinogen) and&#xD;
      fumonisin (a cancer promoter). This clay substance contains of a variety of minerals&#xD;
      including calcium, sodium, potassium, and magnesium. UPSN and similar aluminosilicate&#xD;
      minerals have been regularly used as dietary supplements by humans and animals, and the&#xD;
      safety of this naturally occurring clay substance has been tested in clinical trials. The FDA&#xD;
      treats such minerals or nutritional supplements as a drug when tested for potential of&#xD;
      lessening the likelihood of disease (i.e., potential for mitigating disease).&#xD;
&#xD;
      This study involves the use of an investigational drug called Hydrated Sodium Calcium&#xD;
      Aluminosilicate (ACCS100). &quot;Investigational&quot; means that the &quot;drug&quot; has not yet been approved&#xD;
      by the U.S. Food &amp; Drug Administration (FDA) for reducing harmful effects mycotoxin exposure&#xD;
      in humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This planned clinical trial is a comparative study to determine the safety and effectiveness&#xD;
      of ACCS100 capsules, the investigational product, vs. placebo in participants for the&#xD;
      reduction of dietary mycotoxin exposure. One measure of effectiveness will be the analysis of&#xD;
      the Bexar County participant's AFB1/FB1 metabolite levels in the blood and urine samples.&#xD;
      Additionally, this clinical trial will determine the adherence to the dosing schedule of the&#xD;
      participants; determine the prevalence of mycotoxin exposure in the screened population of&#xD;
      residence of Bexar County, Texas; and compare side-effects and adverse events between ACCS100&#xD;
      and placebo in the participant population. These data will reveal the value of mineral&#xD;
      enterosorbent strategies for the improvement of public health and for the well-being of&#xD;
      humans at risk for dietary mycotoxin exposure and its consequences.&#xD;
&#xD;
      The proposed indication for ACCS100 is &quot;for the reduction of dietary mycotoxin exposure in&#xD;
      humans.&quot;&#xD;
&#xD;
      ACCS100 is made from Hydrated Sodium Calcium Aluminosilicate (HSCAS), a substance generally&#xD;
      recognized as safe (GRAS) by the FDA and has previously been shown to have no significant&#xD;
      adverse effects when given as much as 4 grams per day to healthy study participants or&#xD;
      immuno-compromised cancer patients.&#xD;
&#xD;
      Rationale&#xD;
&#xD;
      Our preliminary studies suggest that ACCS100 contains very low levels of trace metals and&#xD;
      dioxins than are commonly found in smectite clays, and batch-to-batch QA/QC results for this&#xD;
      material are more consistent. We anticipate that ACCS100 can be used as a primary&#xD;
      intervention to bind both AFB1 and FB1 to decrease the external dose of toxins from the diet&#xD;
      and in turn reduce the incidence of hepatic cancer and disease in vulnerable communities.&#xD;
      Using multiple animal models, our laboratory has shown that NS clay is highly effective in&#xD;
      preventing the adverse effects of dietary mycotoxin. Also, Phase I and IIa clinical trials in&#xD;
      Texas and Ghana have confirmed that NS is safe for human consumption and significantly&#xD;
      reduces exposure to both AFB1 and FB1 (Wang et al., 2005; Afriyie-Gyawu et al., 2007, 2008;&#xD;
      Wang et al., 2008; Phillips et al., 2007; Jiang et al., 2008; Jolly et al., 2006; Robinson,&#xD;
      et al., 2009). The incidence of human HCC has been shown to be significantly elevated in&#xD;
      several zip code regions in Bexar County, Texas. Studies conducted by the Agency for Toxic&#xD;
      Substances and Disease Registry indicate that there are several zip code regions within Bexar&#xD;
      County, Texas where the incidence of liver cancer is significantly elevated (ATSDR, 2004).&#xD;
      Notably, age-adjusted cancer incidence rates cited by the Texas Department of State Health&#xD;
      Services from 2002-2006 show that Hispanics in Bexar Co. have an increased HCC incidence&#xD;
      rate, 16.5 (15.0-18.0), compared to Hispanics in Texas, 10.9 (10.4-11.4); rates are per&#xD;
      100,000, and confidence intervals are 95% for rates. Furthermore, the HCC incidence rate for&#xD;
      Bexar Co. Hispanics was considerably higher than all races in Bexar Co., 10.0 (9.2-10.8), and&#xD;
      all races in Texas, 5.8 (5.7-6.0). Hispanic males in Bexar County (compared to females) were&#xD;
      shown to have the highest HCC incidence rate during this time period, at 27.1 (24.2-30.2)&#xD;
      versus 8.4 (7.0-9.9). Chronic exposure to low levels of AFB1 and FB1 contaminated corn and&#xD;
      peanuts, is a major risk factor for the development of HCC, and risk is significantly&#xD;
      increased when exposed individuals are infected with hepatitis virus. An association between&#xD;
      HCC incidence and hepatitis C virus (HCV) infection has been evident in many developed&#xD;
      countries including the U.S., Japan, Egypt, and numerous countries in Europe (Seeff, 2004).&#xD;
      Interestingly, records from the University of Texas M.D. Anderson Cancer Center have shown&#xD;
      that more than 50% of the HCC cases observed in Texas could be attributed to HCV infection&#xD;
      (Hassan, et al., 2002). The HCV prevalence in Texas has been reported to vary from&#xD;
      1.25-2.63%, with higher concentrations in southern Texas and along the Texas-Mexico border&#xD;
      (Yalamanchili, et al., 2005). Armstrong et al. (2000) estimated that in the future HCC&#xD;
      incidence may rise in the U.S. due to the problem of chronic hepatitis C. While prevention of&#xD;
      HCV infection would play a major role in reducing the burden of HCC, currently no vaccine is&#xD;
      available for HCV. Thus, eliminating AFB1/FB1 exposure at an individual level (in the most&#xD;
      vulnerable individuals), may contribute to the overall reduction of HCC risk and burden. In&#xD;
      our recent pilot study, 184 volunteers from a primarily Hispanic community within three zip&#xD;
      codes in Bexar Co. (with a significantly elevated liver cancer incidence rate) provided blood&#xD;
      and urine samples for hepatitis screening and biomarker analyses at the San Antonio&#xD;
      Metropolitan Health District (SAMHD) Environmental Health and Wellness Center (Figure 2). Of&#xD;
      the participants, 7.1% were hepatitis C virus positive, based on anti-HCV antibody&#xD;
      measurement. To assess short-term AFB1 exposure, urinary aflatoxin M1 (AFM1) levels were&#xD;
      measured using high performance liquid chromatography with fluorescence detection. AFM1 was&#xD;
      detectable in 11.7% of urine samples, with the average level at 223.85 ± 250.56 (range&#xD;
      1.89-935.49) pg/mg creatinine. Results from a food frequency questionnaire showed that over&#xD;
      98% of participants reported that they ate fresh corn, canned or frozen corn, corn tortillas,&#xD;
      Mexican food, rice, peanut butter, corn bread, and nuts at various frequencies. A large&#xD;
      percentage of the population (44.8%) consumed corn tortillas frequently (3-14 times per&#xD;
      week), and the majority (57.6%) ate more than 2 tortillas at each time of consumption. The&#xD;
      detection of urinary AFM1 was significantly associated with an increased consumption of&#xD;
      tortillas (p = 0.009), peanuts (p = 0.033) and rice (p = 0.037). Findings suggested that&#xD;
      participants consuming high amounts of foods prone to AFB1/FB1 contamination may potentially&#xD;
      be exposed to these toxins at significant levels. Importantly, strategies that reduce&#xD;
      AFB1/FB1 exposure, especially in individuals infected with hepatitis, may play an important&#xD;
      role in the prevention of HCC in at-risk communities in Texas. These preliminary studies&#xD;
      provide the groundwork and proof of concept for the proposed project. Feasible interventions&#xD;
      and therapies to diminish human exposure to AFB1/FB1 are imperative. In this proposal,&#xD;
      studies will provide an innovative strategy that will reduce dietary mycotoxin exposure. Our&#xD;
      approach will utilize ACCS100 to mitigate dietary exposures to AFB1 (a cancer initiator) and&#xD;
      FB1 (a cancer promoter).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">August 2014</completion_date>
  <primary_completion_date type="Actual">August 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AFB1-lysine Adduct (pg/mg) Overtime</measure>
    <time_frame>3 months on intervention (weeks 0-12); 1 month off intervention (week 16)</time_frame>
    <description>After randomization, participants provided serum samples at baseline, weeks 4, 12, and 16. Week 16 represents one month off treatment.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">234</enrollment>
  <condition>Dietary Carcinogenesis</condition>
  <arm_group>
    <arm_group_label>ACCS100 High Dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ACCS100 Low Dose</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ACCS100</intervention_name>
    <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.</description>
    <arm_group_label>ACCS100 High Dose</arm_group_label>
    <arm_group_label>ACCS100 Low Dose</arm_group_label>
    <other_name>HSCAS</other_name>
    <other_name>UPSN</other_name>
    <other_name>NS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <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.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Calcium Carbonate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        3.1 Participant Inclusion Criteria 3.1.1 Detectable blood AFB1-albumin adduct levels (limit&#xD;
        of detection=0.01 pmol/mg albumin) 3.1.2 18 -85 years 3.1.3 Ability to take oral capsules&#xD;
        3.1.4 Negative urine pregnancy test for women of childbearing age 3.1.5 Must have the&#xD;
        ability to understand and the willingness to provide a written informed consent to&#xD;
        participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        3.2 Participant Exclusion Criteria 3.2.1 History of known allergy to silicates 3.2.2&#xD;
        Pregnancy or lactation 3.2.3 History of significant neurological or psychiatric disorders&#xD;
        that would impede giving consent, treatment, or follow up 3.2.4 Any serious systemic&#xD;
        disorders incompatible with the study 3.2.5 History of chronic disease (ie heart disease,&#xD;
        renal disease). A participant may have a diagnosis of and be managed for diabetes) Any&#xD;
        recent diagnosis of cancer.&#xD;
&#xD;
        3.2.6 Participation in any other clinical study where the participant is actively taking an&#xD;
        investigational medication within the last 30 days&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bradley H Pollock, MPH, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas Health Science Center San Antonio Texas</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Texas Health Science Center Cancer Therapy and Research Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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.</citation>
    <PMID>22324939</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>20870273</PMID>
  </reference>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <results_first_submitted>December 14, 2015</results_first_submitted>
  <results_first_submitted_qc>December 14, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 21, 2016</results_first_posted>
  <last_update_submitted>March 20, 2016</last_update_submitted>
  <last_update_submitted_qc>March 20, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mycotoxins</keyword>
  <keyword>Aflatoxin</keyword>
  <keyword>Fumonisin</keyword>
  <keyword>Aflatoxicosis</keyword>
  <keyword>Dietary</keyword>
  <keyword>Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinogenesis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Calcium Carbonate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Study submitted for publication in Tier 1 Toxicology Journal</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Randomized, double blind, placebo controlled clinical trial of ACCS100 for the prevention of cancer associated with dietary Aflatoxin exposure. Recruitment occurred in Bexar and Medina Counties, Texas, USA from August 2012 through August 2014. The number of participants was 234 and 143 finished the study.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>ACCS100 High Dose</title>
          <description>Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="P2">
          <title>ACCS100 Low Dose</title>
          <description>Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="P3">
          <title>Placebo</title>
          <description>Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.&#xD;
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.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="71"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="80"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="51"/>
                <participants group_id="P3" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Pregnancy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants had detectable levels of aflatoxin in serum sample and were otherwise healthy.</population>
      <group_list>
        <group group_id="B1">
          <title>ACCS100 High Dose</title>
          <description>Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="B2">
          <title>ACCS100 Low Dose</title>
          <description>Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="B3">
          <title>Placebo</title>
          <description>Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="71"/>
            <count group_id="B2" value="83"/>
            <count group_id="B3" value="80"/>
            <count group_id="B4" value="234"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="80"/>
                    <measurement group_id="B4" value="234"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.1" spread="13.8"/>
                    <measurement group_id="B2" value="39.2" spread="13.9"/>
                    <measurement group_id="B3" value="42.2" spread="13.6"/>
                    <measurement group_id="B4" value="41.1" spread="13.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="63"/>
                    <measurement group_id="B3" value="64"/>
                    <measurement group_id="B4" value="180"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="80"/>
                    <measurement group_id="B4" value="234"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AFB1-lysine Adduct (pg/mg) Overtime</title>
        <description>After randomization, participants provided serum samples at baseline, weeks 4, 12, and 16. Week 16 represents one month off treatment.</description>
        <time_frame>3 months on intervention (weeks 0-12); 1 month off intervention (week 16)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ACCS100 High Dose</title>
            <description>Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.&#xD;
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.</description>
          </group>
          <group group_id="O2">
            <title>ACCS100 Low Dose</title>
            <description>Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.&#xD;
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.</description>
          </group>
          <group group_id="O3">
            <title>Placebo</title>
            <description>Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.&#xD;
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.</description>
          </group>
        </group_list>
        <measure>
          <title>AFB1-lysine Adduct (pg/mg) Overtime</title>
          <description>After randomization, participants provided serum samples at baseline, weeks 4, 12, and 16. Week 16 represents one month off treatment.</description>
          <units>pg/mg albumin</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="71"/>
                <count group_id="O2" value="83"/>
                <count group_id="O3" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.77" spread="2.52"/>
                    <measurement group_id="O2" value="4.09" spread="2.25"/>
                    <measurement group_id="O3" value="4.26" spread="3.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" spread="1.30"/>
                    <measurement group_id="O2" value="2.62" spread="1.08"/>
                    <measurement group_id="O3" value="3.06" spread="1.66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.87" spread="1.53"/>
                    <measurement group_id="O2" value="2.71" spread="1.35"/>
                    <measurement group_id="O3" value="3.22" spread="1.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.74" spread="1.44"/>
                    <measurement group_id="O2" value="2.99" spread="1.26"/>
                    <measurement group_id="O3" value="3.03" spread="1.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The time fame for AE observations was baseline to follow-up period. 120 days total time with 90 days on treatment and 30 day follow-up.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ACCS100 High Dose</title>
          <description>Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="E2">
          <title>ACCS100 Low Dose</title>
          <description>Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.&#xD;
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.</description>
        </group>
        <group group_id="E3">
          <title>Placebo</title>
          <description>Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.&#xD;
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.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="71"/>
                <counts group_id="E2" subjects_affected="47" subjects_at_risk="83"/>
                <counts group_id="E3" subjects_affected="38" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Indigestion, reflux, heartburn</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="71"/>
                <counts group_id="E2" events="9" subjects_affected="8" subjects_at_risk="83"/>
                <counts group_id="E3" events="10" subjects_affected="8" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="71"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="83"/>
                <counts group_id="E3" events="4" subjects_affected="3" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="71"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="83"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="10" subjects_affected="10" subjects_at_risk="71"/>
                <counts group_id="E2" events="21" subjects_affected="13" subjects_at_risk="83"/>
                <counts group_id="E3" events="9" subjects_affected="7" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Abdominal Discomfort</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="30" subjects_affected="16" subjects_at_risk="71"/>
                <counts group_id="E2" events="32" subjects_affected="22" subjects_at_risk="83"/>
                <counts group_id="E3" events="25" subjects_affected="20" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="71"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="83"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Unlike our clinical trials in Africa, where maximum compliance was achieved through the daily in-home monitoring, the current study relied on participant reports during monthly visits in which total compliance was difficult to assess.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Bradley H. Pollock, PI</name_or_title>
      <organization>University of Texas Health Science Center at San Antonio / University of California, Davis* current</organization>
      <phone>(530) 752-7250</phone>
      <email>pbollock@ucdavis.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01677195
org study id: TxESI 12-001
nct id: NCT01677195
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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.
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).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Investigator)
measure: AFB1-lysine Adduct (pg/mg) Overtime
time frame: 3 months on intervention (weeks 0-12); 1 month off intervention (week 16)
description: After randomization, participants provided serum samples at baseline, weeks 4, 12, and 16. Week 16 represents one month off treatment.
arm group label: ACCS100 High Dose
arm group type: Active Comparator
description: Participants will receive a total daily dose of 3 grams of ACCS100; 1 gram three times a day with meals.
arm group label: ACCS100 Low Dose
arm group type: Active Comparator
description: Participants will receive a total daily dose of 1.5 grams of ACCS100; 500 mgs three times a day with meals.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo capsules shown not to absorb mycotoxins three times a day with meals.
intervention type: Drug
intervention name: ACCS100
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.
arm group label: ACCS100 High Dose
arm group label: ACCS100 Low Dose
other name: HSCAS
other name: UPSN
other name: NS
intervention type: Drug
intervention name: Placebo
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.
arm group label: Placebo
other name: Calcium Carbonate
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Bradley H Pollock, MPH, Ph.D.
role: Principal Investigator
affiliation: University of Texas Health Science Center San Antonio Texas
facility: 
country: United States
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.
PMID: 22324939
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.
PMID: 20870273
responsible party type: Sponsor
mesh term: Carcinogenesis
mesh term: Calcium Carbonate
sharing ipd: Yes
ipd description: Study submitted for publication in Tier 1 Toxicology Journal
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Unlike our clinical trials in Africa, where maximum compliance was achieved through the daily in-home monitoring, the current study relied on participant reports during monthly visits in which total compliance was difficult to assess.
point of contact: 