Selenium in the Treatment of Arsenic Toxicity and Cancers (SETAC)

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

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.

Study Overview

• Status: Completed
• Conditions: Arsenical Melanosis; Arsenical Keratosis; Arsenical Cancers; Arsenicosis; Arsenic Exposure; Arsenic Toxicity; Arsenic Poisoning
• Intervention / Treatment: Drug: placebo; Drug: sodium selenite

• Study Type: Interventional
• Enrollment (Actual): 819
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bangladesh
  • Chandpur District
    • Kalibari town, Chandpur District, Bangladesh
      • SETAC Trial Field Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Texas Tech University
• Collaborators: National Cancer Institute (NCI); American Cancer Society, Inc.
• Investigators: Principal Investigator: Julian E Spallholz, PhD, Texas Tech University; Principal Investigator: Paul F La Porte, PhD, Pritzker School of Medicine, The University of Chicago; Principal Investigator: Selim Ahmed, MBBS, FCPS, Institute of Child & Mother Health, Dhaka, Bangladesh

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 27, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Estimate): October 7, 2011
• Last Update Submitted That Met QC Criteria: October 6, 2011
• Last Verified: October 1, 2011

More Information

Terms related to this study

• Keywords: drinking water; arsenical melanosis; arsenical melanoses; arsenical keratosis; arsenical keratoses; arsenical cancer; arsenic cancers; arsenic; arsenicosis; arsenic exposure; arsenic toxicity; arsenic poisoning; selenium; selenite; sodium selenite
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Nervous System Diseases; Skin Diseases; Neoplasms; Precancerous Conditions; Hyperpigmentation; Pigmentation Disorders; Neurotoxicity Syndromes; Heavy Metal Poisoning, Nervous System; Poisoning; Keratosis, Actinic; Keratosis; Melanosis; Arsenic Poisoning; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Trace Elements; Micronutrients; Antioxidants; Selenious Acid; Sodium Selenite; Selenium
• Other Study ID Numbers: TTU-JES-1; 1R21CA117111-01 (U.S. NIH Grant/Contract); ROG-06-098-01 (Other Grant/Funding Number: The American Cancer Society)