Selenium and Arsenic Pharmacodynamics
Condition: Arsenic Poisoning Chronic
MeSH terms: Arsenic Poisoning; Poisoning
Study type: Interventional
Phase: Phase 1/Phase 2

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 description: 
      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 selenium can
      remove arsenic from victims' bodies. 40 volunteer arsenicosis sufferers will be housed in a
      local private in-patient clinic for 10 consecutive days. While in the clinic, they will
      follow a fixed, communal diet consisting of drinking water and meals from their village. On
      the 6th day in the clinic investigators will give a single dose of either placebo (table
      salt, 0.8 mg) or anhydrous sodium selenite (0.8 mg selenium) labelled with a non-radioactive
      naturally occurring isotope (77Se), to distinguish it from selenium already in the body.
      Placebo and anhydrous sodium selenite look similar and taste very much alike. Placebo or
      anhydrous sodium selenite will be supplied in a powdered form at the bottom of a glass and
      diluted by 100 ml of purified water immediately before being ingested by participants under
      close control by the clinical staff. The investigators will analyze arsenic and selenium
      levels in feces, urine and blood samples before and after the dose, and will use molecular
      speciation analyses to determine their chemical form in blood, urine and feces. Also,
      investigators will analyze arsenic and selenium levels in finger- and toenails and hair at
      the beginning of the trial as a possible biomarker of As exposure.
    

Intervention name(s): Anhydrous selenite; Sodium chloride
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 40 volunteer sufferers will be housed in a local private in-patient clinic where they will follow a fixed, communal diet consisting of drinking water and meals from their village. On a 6th day we will give a single dose of placebo (sodium chloride) or anhydrous sodium selenite (0.8mg selenium) labelled with a non-radioactive naturally occurring isotope (77Se), to distinguish it from selenium already in the body.; 40 volunteer sufferers will be housed in a local private in-patient clinic where they will follow a fixed, communal diet consisting of drinking water and meals from their village. On a 6th day we will give a single dose of placebo (sodium chloride) or anhydrous sodium selenite (0.8mg selenium) labelled with a non-radioactive naturally occurring isotope (77Se), to distinguish it from selenium already in the body.
Other intervention name(s): Sodium selenite anhydrous; Table salt
Intervention MeSH terms: Selenious Acid; Sodium Selenite
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Arsenic; Arsenicosis