Safety and Efficacy of a Novel Xanthine Oxidase/Xanthine Dehydrogenase Inhibitor in the Treatment of Gout

Summary: The internship report is based on the activities completed during the Internship Practicum at the Department of Internal Medicine, Division of Rheumatology, at the University of North Texas Health Science Center at Fort Worth and at the Rheumatology Clinic at John Peter Smith Hospital. This internship serves as partial training in the area of Clinical Research Management and focuses on studies involving rheumatic diseases, with specific emphasis on Gout. Specific Aims/Hypothesis: Ongoing clinical trials in the Department of Internal Medicine Rheumatology clinic are the bases for the project which focuses on the treatment of gout and a proprietary study on the uses of a novel xanthine oxidase/ xanthine dehydrogenase inhibitor (XOD/XDH inhibitor) to relieve the symptoms of gout. The particular research is a phase three study to assess the safety and efficacy of a novel xanthine oxidase/ xanthine dehydrogenase inhibitor compared to a placebo and an established xanthine oxidase/ xanthine dehydrogenase inhibitor, allopurinol. The hypothesis of the study is that the new XOD/XDH inhibitor will be more effective at lowering uric acid levels and thus will reduce the frequency of gout more effectively and with fewer side effects than traditional treatment or a placebo. Under the direction of the Department of Internal Medicine, subjects who met inclusion/exclusion criteria of the study were randomly assigned to be treated with colchicine in addition to either allopurinol, or the novel compound, which hereafter will be referred to as the novel XOD/XDH inhibitor, or to a placebo. The safety and efficacy of the novel XOD/XDH inhibitor will be compared to the traditional drug of choice allopurinol, a uric acid lowering agent, and to a placebo. The placebo is an inactive pill that is designed to look and taste like either allopurinol or the novel XOD/XDH inhibitor. While the period of the internship is not long enough to complete the study and thereby assess the reliability of the hypothesis, the internship and this report have two specific aims: (1) to perform a literature search of gout and related topics and (2) to understand and perform activities of a clinical research coordinator as they relate to the novel XOD/XDH inhibitor study and to other clinical trials in rheumatology. The literature search focuses on specific areas concerned with details about gout: history, epidemiology, forms, causes, signs and symptoms, clinical diagnosis, differential diagnosis, complications, therapeutics (past, present, and future), prevention, associations, cellular mechanisms involved in hyperuricemia, as well as inflammation. The project also provides a description of the activities involved in clinical research, and discusses specifically the roles of the various personnel: Clinical Trials Coordinator, Principle Investigator, Sub-investigator, Institutional Review Board, and Clinical Trials Monitor as they have been involved in the novel XOD/XDH inhibitor study and other studies in rheumatology. Significance: Finding a new treatment for gout is of significant importance for several reasons. In countries with a high standard of living, such as the United States, prevalence of gout has increased and is probably the second most common form of inflammatory arthritis. Gout can result in significant short-term disability, occupational limitations, and increased utilization of medical services therefore making the disease a significant public health problem. New treatment options could greatly improve the prognosis for patients and in addition reduce the cost of the disease by preventing loss of wages due to patient absence from work, for example. Furthermore, new treatments for gout could provide patients with safer therapeutics alternatives than the traditional treatments.