Selenium and Arsenic Pharmacodynamics

NCT02377635 | Completed Phase 1 DMC

• 2 other identifiers: 14-284Grand Challenges Canada/7315
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Arsenic Poisoning Chronic

Keywords

Arsenic; Arsenicosis

Outcome Measures

Primary Outcomes (3)

• Blood As and Se concentrations and chemistry

  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.

  10 days

• Urinary As and Se concentrations and chemistry

  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.

  10 days

• Fecal As and Se concentrations and chemistry

  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.

  10 days

Secondary Outcomes (4)

• The absolute concentrations of 77Se and the ratios (total Se/77Se) and (As/77Se) determined in blood, at each time point of the study.

  10 days

• The absolute concentrations of 77Se and the ratios (total Se/77Se) and (As/77Se) determined in urine, at each time point of the study.

  10 days

• The absolute concentrations of 77Se and the ratios (total Se/77Se) and (As/77Se) determined in feces, at each time point of the study.

  10 days

• Arsenic and selenium concentrations in hair, finger- and toenails

  1 day

Study Arms (2)

Treatment

EXPERIMENTAL

Drug: Anhydrous selenite (Se-77), single dose 0.8mg, orally administered as a 100 ml purified water solution

Dietary Supplement: Anhydrous selenite

Control

PLACEBO COMPARATOR

Drug: Placebo sodium chloride (table salt), orally administered as a 100 ml purified water solution

Dietary Supplement: Sodium chloride

Interventions

Anhydrous selenite DIETARY_SUPPLEMENT

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.

Also known as: Sodium selenite anhydrous

Treatment

Sodium chloride DIETARY_SUPPLEMENT

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.

Also known as: Table salt

Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participants in this study are
• healthy adult (18-65 years of age) male Bangladeshi volunteers from Laksam Upazila,
• who are exposed to arsenic through their normal source of drinking water;
• who are otherwise healthy except that show some signs of chronic arsenic toxicity (arsenicosis);
• have not consumed selenium-containing supplements with last 6 months;
• not concurrently participating or have participated in any other clinical trial within at least 30 days of registration to the current trial.

You may not qualify if:

• Recent history of consuming selenium, concurrent participation or recent participation in any other clinical trial within at least 30 days of registration to the current trial, and people who recently moved in the area.
• Prior clinical trial, recruits will undertake a medical examination by physician. Since chronic kidney disease and alcoholic and viral cirrhosis are common in rural Bangladesh and both conditions might impact selenium and arsenic metabolism, recruits will also be screened through a baseline CMP (Comprehensive Metabolic Panel) , CBC (Complete Blood Count), and INR (International Normalized Ratio of Prothrombin Time as Liver Function Test) panel. Evidence or history of significant hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, musculoskeletal, immunologic, neurologic or dermatologic disease (including drug allergies that are clinically significant) which, by opinion of investigators, could pose a risk to the safety of the individual or the valid conduct of the study will exclude recruits from the participation.
• Current evidence of or history of cancer; evidence of hepatitis B, hepatitis C, human immunodeficiency virus (HIV) infection upon serological testing; evidence of active communicable disease or febrile illness (e.g., bronchopulmonary, urinary or gastrointestinal) within 7 days prior to study will exclude recruits from participation.

Sponsors & Collaborators

• University of Saskatchewan: lead
• University of Chicago: collaborator
• University of Calgary: collaborator
• University of Alberta: collaborator
• Emory University: collaborator
• Wagner College, Staten Island, NY, USA: collaborator
• Applied Speciation and Consulting LLC, WA, USA: collaborator

Study Sites (1)

Unity Hospital Pvt LTD

Lākshām, Comilla, 3570, Bangladesh

Location

Related Publications (4)

• Gailer J, George GN, Pickering IJ, Prince RC, Younis HS, Winzerling JJ. Biliary excretion of [(GS)(2)AsSe](-) after intravenous injection of rabbits with arsenite and selenate. Chem Res Toxicol. 2002 Nov;15(11):1466-71. doi: 10.1021/tx025538s.

  PMID: 12437338 BACKGROUND

• Manley SA, George GN, Pickering IJ, Glass RS, Prenner EJ, Yamdagni R, Wu Q, Gailer J. The seleno bis(S-glutathionyl) arsinium ion is assembled in erythrocyte lysate. Chem Res Toxicol. 2006 Apr;19(4):601-7. doi: 10.1021/tx0503505.

  PMID: 16608173 BACKGROUND

• Prince RC, Gailer J, Gunson DE, Turner RJ, George GN, Pickering IJ. Strong poison revisited. J Inorg Biochem. 2007 Nov;101(11-12):1891-3. doi: 10.1016/j.jinorgbio.2007.06.008. Epub 2007 Jun 13.

  PMID: 17644180 BACKGROUND

• Carew MW, Leslie EM. Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium. Carcinogenesis. 2010 Aug;31(8):1450-5. doi: 10.1093/carcin/bgq125. Epub 2010 Jun 27.

  PMID: 20584751 BACKGROUND

MeSH Terms

Interventions

Sodium Chloride; Sodium Chloride, Dietary

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Sodium, Dietary

Study Officials

• Graham N George, D.Phil.

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D.

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: March 3, 2015
• Study Start: February 10, 2015
• Primary Completion: December 19, 2016
• Study Completion: January 19, 2017
• Last Updated: October 30, 2017

Record last verified: 2017-10

Locations

BA (1)