Chronic Rhinosinusitis (CRS) is a frequently reported chronic disease with sinus inflammation persisting more than 12 weeks. No medication has FDA approval to treat CRS. Major controversies in the diagnosis and treatment of CRS include etiology, classification, and assessment of disease severity. Three hypotheses for etiology have been proposed: allergic inflammation in response to airborne allergens; T cell activation and local IgE production in response to bacterial superantigens; and immune cell activation in the response of CRS patients to fungal antigens in sinus mucus. To address the possible fungal etiology of CRS, several controlled and open-label clinical trials have previously tested intranasal antifungal agents as a potential therapy for CRS. However, the results from these studies are conflicting. To resolve these controversies, this R34 Clinical Trial Planning Grant proposes to develop a prospective, multicenter, double-blind, placebo-controlled clinical trial to investigate the efficacy of oral itraconazole in patients with CRS with nasal polyps. This novel study will propose that after a 6-week run-in period, CRS patients will be treated with oral itraconazole (400 mg daily) or placebo for 12 weeks.
The specific aims i nclude establishing a multicenter research team from 6 different medical centers, defining patient recruitment strategies, developing the study protocol, writing the investigator's brochure and the manual of operations/procedures, and developing tools for data management and research oversight. To address the controversies regarding classification and assessment of CRS severity, the inclusion criteria for patients will be defined precisely based on recent consensus descriptions. A standardized treatment protocol will be used throughout all the study centers, which will be separated geographically. Both conventional monitoring tools and original strategies will be proposed to investigate the efficacy of oral intraconazole in patients with CRS with nasal polyps. The goals of this clinical trial will be as follows: 1) to study the clinical and immunological efficacy of oral itraconazole treatment, and 2) to identify clinical parameters for those patients who are benefited by the treatment. Completion of this project will produce the U01 application, namely the NIAID Clinical Trial Implementation Cooperative Agreement, incorporating all the developed elements. The ultimate goals for this effort are to develop novel treatment and preventive approaches for CRS patients. This study will directly impact both the clinical practice and decisions in CRS and will help to provide specific and effective therapies for this common, costly, and incapacitating disorder. This proposal will establish 6 medical teams from different areas of the U.S. to study a new treatment method for chronic rhinosinusitis. It will provide these teams with a consistent and coherent set of research guidelines to test both the safety and the effectiveness of an antifungal medication taken by mouth and to investigate the cause of the chronic rhinosinusitis in patients. ? ? ?
