Clinical Trial in Bangladesh
Conducting an NIH-supported Clinical Trial
By Paul LaPorte, MS 2
Paul LaPorte, MS 2
The clinical trial that I am directing will assess whether dietary selenite is efficacious in countering the toxicity of chronic arsenic exposure. With the exception of a handful of rural counties in the Southwest, drinking water arsenic is not a health issue in the US. However, several countries, including Bangladesh, India, Argentina, and pockets of Taiwan and Mexico have geologically-contaminated aquifers. Bangladesh's arsenic problem is the largest and most acute in the world. About 40 million inhabitants are exposed to arsenic at concentrations about 50 parts per billion, according to a well respected national survey conducted by the British Geological Survey in 1998. Fifty parts per billion is a "red line" for increased risk of developing signs of arsenical melanosis, arsenical keratosis, and skin, lung, and urinary tract cancers. There is about a 1-2% lifetime prevalence of arsenical cancers in those exposed above 50 ppb, and a much wider prevalence of arsenical melanosis and keratosis, which has a very unique distribution that is sometimes mistaken by villagers for leprosy. Due to Bangladesh's rural poverty, the arsenical cancers are not diagnosed until the terminal stages, most patients die a few months thereafter. Selenium is recognized as an anti-oxidant because it comprises the catalytic site of Glutathione Peroxidase. For this reason, it is often included in vitamins and food supplements. At the Bookstore Starbucks, in fact, you can find a line of drinks that proudly include selenium.
What is much less well-known is that selenium has a peculiar chemical antagonism with arsenic. This phenomena has been observed in arsenic-intoxicated mice, rats, rabbits, and human cell cultures in dozens of in Bangladesh experiments spanning thirty years. Mechanisms were proposed but not supported by molecular evidence until a group of Canadian nuclear chemists (J. Gailer, I.Pickering, and G. George) discovered a new metabolite, the (GS)2AsSe-compound. This is an insoluble complex of arsenic, selenium and glutathione that is rapidly excreted in the bile of arsenic-intoxicated rabbits. We believe that this is the basis for selenium's ability to protect against arsenic toxicity, with the Gluthatione Peroxidase pathway playing a secondary role.
Team members in field with villagers/patients
The trial that is underway is a randomized, double-blind, placebo-controlled Phase III trial to assess whether dietary selenite reduces arsenical melanosis after 48 weeks. It is being conducted by a consortium of American, Bangladeshi, and Canadian scientists. Grant proposal writing and coordination/directing has been my responsibility. The field work is directed by a Bangladeshi pediatrician, Dr. Selim Ahmed, and the chemical analysis is directed by a Bangladeshi-American chemist, Professor Mohammed Alauddin. The Principal Investigator is Professor Julian Spallholz of Texas Tech University.
We are aiming for the "gold standard" in clinical trials because previous Phase II trials conducted in China and Bangladesh by other groups were so inadequately designed that their encouraging results are not definitive answers. We are examining selenium's affect on ameliorating melanosis as a surrogate marker for Basal and Squamous Cell Carcinomas, which take five to ten years to develop in drinking-water arsenic patients. The trial itself involves 800 adults and adolescents, and is supported by the NCI/NIH and the American Cancer Society. It is scheduled to conclude in January 2008. More information is available at: www.bangladesh-selenium.org
