Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Selenium and Arsenic Pharmacodynamics (SEASP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02377635
Recruitment Status : Completed
First Posted : March 3, 2015
Last Update Posted : October 30, 2017
Sponsor:
Collaborators:
University of Chicago
University of Calgary
University of Alberta
Emory University
Wagner College, Staten Island, NY, USA
Applied Speciation and Consulting LLC, WA, USA
Information provided by (Responsible Party):
Graham George, University of Saskatchewan

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.

Condition or disease Intervention/treatment Phase
Arsenic Poisoning Chronic Dietary Supplement: Anhydrous selenite Dietary Supplement: Sodium chloride Phase 1 Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Selenium and Arsenic Pharmacodynamics
Study Start Date : February 10, 2015
Actual Primary Completion Date : December 19, 2016
Actual Study Completion Date : January 19, 2017


Arm Intervention/treatment
Experimental: Treatment
Drug: Anhydrous selenite (Se-77), single dose 0.8mg, orally administered as a 100 ml purified water solution
Dietary Supplement: Anhydrous selenite
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 Name: Sodium selenite anhydrous

Placebo Comparator: Control
Drug: Placebo sodium chloride (table salt), orally administered as a 100 ml purified water solution
Dietary Supplement: Sodium chloride
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 Name: Table salt




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

The participants in this study are

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

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02377635


Locations
Layout table for location information
Bangladesh
Unity Hospital Pvt LTD
Laksam, Comilla, Bangladesh, 3570
Sponsors and Collaborators
University of Saskatchewan
University of Chicago
University of Calgary
University of Alberta
Emory University
Wagner College, Staten Island, NY, USA
Applied Speciation and Consulting LLC, WA, USA
Investigators
Layout table for investigator information
Principal Investigator: Graham N George, D.Phil. University of Saskatchewan

Publications:
Layout table for additonal information
Responsible Party: Graham George, Ph.D., University of Saskatchewan
ClinicalTrials.gov Identifier: NCT02377635     History of Changes
Other Study ID Numbers: 14-284
Grand Challenges Canada/7315 ( Other Grant/Funding Number: Government of Canada )
First Posted: March 3, 2015    Key Record Dates
Last Update Posted: October 30, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Graham George, University of Saskatchewan:
Arsenic
Arsenicosis

Additional relevant MeSH terms:
Layout table for MeSH terms
Poisoning
Arsenic Poisoning
Chemically-Induced Disorders
Heavy Metal Poisoning, Nervous System
Neurotoxicity Syndromes
Nervous System Diseases
Selenium
Selenious Acid
Sodium Selenite
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Trace Elements
Micronutrients
Nutrients
Growth Substances