Selenium and Arsenic Pharmacodynamics

NCT ID: NCT02377635

Last Updated: 2017-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-10

Study Completion Date

2017-01-19

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Arsenic Poisoning Chronic

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Arsenic Arsenicosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Treatment

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

Group Type EXPERIMENTAL

Anhydrous selenite

Intervention Type 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.

Control

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

Group Type PLACEBO_COMPARATOR

Sodium chloride

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Sodium selenite anhydrous Table salt

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

University of Chicago

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role collaborator

University of Alberta

OTHER

Sponsor Role collaborator

Emory University

OTHER

Sponsor Role collaborator

Wagner College, Staten Island, NY, USA

UNKNOWN

Sponsor Role collaborator

Applied Speciation and Consulting LLC, WA, USA

UNKNOWN

Sponsor Role collaborator

University of Saskatchewan

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Graham George

Ph.D.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Graham N George, D.Phil.

Role: PRINCIPAL_INVESTIGATOR

University of Saskatchewan

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Unity Hospital Pvt LTD

Lākshām, Comilla, Bangladesh

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Bangladesh

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 12437338 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16608173 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17644180 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20584751 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Grand Challenges Canada/7315

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

14-284

Identifier Type: -

Identifier Source: org_study_id