Selenium in the Treatment of Arsenic Toxicity and Cancers

Study Overview
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Brief Summary
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Context: Approximately 100 million people throughout the world consume water contaminated with arsenic at levels above carcinogenic thresholds, including 40 million in Bangladesh alone, with up to one-fourth of deaths attributed to arsenic exposure in the worst-affected regions. There are no proven therapies for treating chronic arsenic toxicity or for preventing arsenical cancers. Selenium has been known to counter arsenic toxicity in a variety of animal models. The investigators have recently shown in animals and humans that this effect is mediated by the formation of [(GS)2AsSe]- , the seleno-bis(S-glutathionyl) arsinium ion, which is then rapidly excreted via the hepatobiliary system. Concurrently, two Phase II studies in China and Bangladesh have suggested clinical benefit to selenium supplementation in arsenicosis patients. Objective: To assess whether daily selenium supplementation counters arsenic toxicity in patients exposed to drinking water arsenic. If proven effective, selenium supplementation might be safely and cost-effectively implemented in the worst-affected localities.

Official Title
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Selenite in the Detoxification of Arsenic and the Prevention of Arsenical Melanosis and Cancers Amongst Bangladeshi Arsenicosis Patients: A 48-week, Randomized, Double-blinded, Placebo-controlled Phase III Trial

Conditions
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Arsenical Melanosis, Arsenical Keratosis, Arsenical Cancers, Arsenicosis, Arsenic Exposure, Arsenic Toxicity, Arsenic Poisoning

Intervention / Treatment
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* Drug: sodium selenite
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Resident of Bangladesh in an arsenic-affected region (Chandpur) Age between 12 and 55 Exposure to arsenic in home drinking water greater than 50 ug/L. Arsenical melanosis on the torso confirmed by epiluminescence microscopy Exclusion Criteria: Recent history or plans to consume selenium-containing supplements Anticipated change in home drinking water supply during study period

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Patients who receive control (placebo) | Drug: placebo<br>* dicalcium phosphate capsule matching the selenium capsule in appearance; consumed once daily with breakfast<br>|
| Active Comparator: Selenium<br>Patients who receive treatment (selenium) | Drug: sodium selenite<br>* 200 micrograms (µg) of selenium in the form of sodium selenite; capsule form consumed once daily with breakfast.<br>* Other names: selenite;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in arsenical melanosis | Arsenical melanosis was recorded in 4 quadrants of each patients' torsos using the Dermlite epiluminescence microscopy system. The images were then scored in a blinded, randomized fashion by a dermatologist. | 0 weeks (baseline), 24 weeks, and 48 weeks (end) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in blood arsenic levels | The levels of arsenic in patients' blood was measured to determine whether intervention had a differential effect. | week 0, week 24 and week 48 | 
| changes in urinary arsenic levels | The levels of arsenic in patients' urine was measured to determine whether intervention had a differential effect. | week 0, week 24 and week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arsenical melanosis, arsenical melanoses, arsenical keratosis, arsenical keratoses, arsenical cancer, arsenic cancers, arsenic, arsenicosis, arsenic exposure, arsenic toxicity, arsenic poisoning, drinking water, selenium, selenite, sodium selenite