Clinical Trial: Selenium and Arsenic Pharmacodynamics

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Selenium and Arsenic Pharmacodynamics

Brief Summary: This clinical trial should prove that selenium can treat arsenic exposure in humans by promoting excretion. The new trial differs from previous trials in that participants will be maintained in a local clinic and provided with food and water from their home villages. The purpose of this study to determine the fate of selenium supplements in feces, urine and blood of volunteers living in conditions of high arsenic load in drinking water. The use of a clinic will enable monitoring of all intake and excretion of both arsenic and selenium, and will ensure that participants take their selenium doses or placebo as appropriate. This proof of concept is absolutely essential groundwork for any remediation strategy involving selenium supplements.

Detailed Summary:

Main Purpose:

Determine the fate of selenium supplements in feces, urine and blood through a new Phase I/II clinical trial pharmacodynamics study in Bangladesh. This will include conventional analysis of feces, urine and blood samples, tracing the fate of selenium by administering isotopically enriched 77Se (a naturally occurring non-radioactive stable isotope). The use of 77Se will allow us to discriminate between endogenous selenium already in the bodies of the trial participants (patients) from the administered selenium given to the patients.

Clinical Trial Hypotheses:

  • In a group of patients exhibiting symptoms of arsenicosis (chronic low-level arsenic poisoning), a single, elevated dose of anhydrous sodium selenite leads to excretion of arsenic at levels significantly higher than patients receiving placebo.
  • In the selenite-supplemented (treatment) group, the total arsenic excreted is significantly higher than that consumed in the diet and drinking water.
  • In the treatment group, selenium co-excreting with arsenic originates from the administered selenium supplement, rather than from endogenous selenium.
  • The ratio of arsenic to selenium in the feces, urine and blood of the treatment group following administration of the selenium supplement is approximately 1:1, consistent with the formation of the discrete molecular entity, the seleno bis-S-glutathionyl arsinium anion discovered in the investigators' earlier animal experiments.

The process to be followed:

A tightly controlled Phase I/II clinical trial in Bangladesh to prove that sel
Sponsor: University of Saskatchewan

Current Primary Outcome:

  • Blood As and Se concentrations and chemistry [ Time Frame: 10 days ]
    The ICPMS technique will be used to analyze arsenic and selenium levels in blood samples before and after the dose. The molecular speciation analyses (IC-ICP-MS) will be applied to determine their chemical form in blood.
  • Urinary As and Se concentrations and chemistry [ Time Frame: 10 days ]
    The ICPMS technique will be used to analyze arsenic and selenium levels in urine samples before and after the dose. The molecular speciation analyses (IC-ICP-MS) will be applied to determine their chemical form in urine.
  • Fecal As and Se concentrations and chemistry [ Time Frame: 10 days ]
    The ICPMS technique will be used to analyze arsenic and selenium levels in feces samples before and after the dose. The molecular speciation analyses (IC-ICP-MS) will be applied to determine their chemical form in feces.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The absolute concentrations of 77Se and the ratios (total Se/77Se) and (As/77Se) determined in blood, at each time point of the study. [ Time Frame: 10 days ]
    Quantitative analysis (ICP-MS) of As, 77Se and total Se to evaluate the effect of Se supplementation on binding and excretion of arsenic as opposed to the mobilization of endogenous Se in a body.
  • The absolute concentrations of 77Se and the ratios (total Se/77Se) and (As/77Se) determined in urine, at each time point of the study. [ Time Frame: 10 days ]
    Quantitative analysis (ICP-MS) of As, 77Se and total Se to evaluate the effect of Quantitative analysis (ICP-MS) of As, 77Se and total Se to evaluate the effect of Se supplementation on excretion of arsenic as opposed to the mobilization of endogenous Se in a body.
  • The absolute concentrations of 77Se and the ratios (total Se/77Se) and (As/77Se) determined in feces, at each time point of the study. [ Time Frame: 10 days ]
    Quantitative analysis (ICP-MS) of As, 77Se and total Se to evaluate the effect of Se supplementation on excretion of arsenic as opposed to the mobilization of endogenous Se in a body.
  • Arsenic and selenium concentrations in hair, finger- and toenails [ Time Frame: 1 day ]
    Quantitative analysis (ICP-MS) of As and Se content in keratinous tissues as a possible biomarker of As exposure


Original Secondary Outcome: Same as current

Information By: University of Saskatchewan

Dates:
Date Received: February 10, 2015
Date Started: February 2015
Date Completion: July 2016
Last Updated: May 13, 2016
Last Verified: May 2016