Infections caused by protozoan parasites of the genus Leishmania include cutaneous (CL), mucosal (ML) and visceral leishmaniasis (VL). Over 12 million people are currently suffering from leishmaniasis, and approximately 2 million new cases occur annually, making it a major global health problem. Recently, CL has been seen in canine populations in the US as well as army personnel serving in Iraq and Afghanistan. Systemic pentavalent antimonials such as sodium stibogluconate (SSG) are the recommended treatment for CL world-wide, but they are toxic, and compliance with treatment is poor because daily injections for 3 weeks or longer are required. Furthermore, in immunocompromised individuals antimonial treatment is associated with relapses. We are interested in novel treatments for CL that are safe, easy to administer and effective in inducing long-term cure. Recently, radio-frequency-induced heat (RFH) therapy has been used in the treatment of CL. This treatment delivers controlled and localized radiofrequencies into lesions for 30-60 seconds under local anesthesia. Several short-term follow-up (4-5 months) studies and one long-term follow-up (12 months) study involving US soldiers who were infected with L. major in Iraq found that RFH therapy was comparable, or even better, than systemic antimonial therapy. We recently found that RFH therapy was also effective in inducing cure of CL in HIV-infected patients who were refractory to SSG. Furthermore, we found that RFH therapy induced complete clinical cure in nearly 98% of immunocompetent CL patients by 6 months with no relapses for up to 1 year. These findings suggest that RFH therapy should be effective in inducing long-term cure of CL in immunocompetent as well as immunocompromised patients, and could therefore represent a novel first line of treatment. However, a clinical trial is needed o determine cure rates and establish long-term efficacy of RFH therapy in treatment of CL caused by other Leishmania species that are difficult to treat with conventional drugs, and to determine the risk of disease recurrence (if any) in patients living in Leishmania endemic regions. The goal of this R34 application is to plan an open-label phase III clinical trial to compare the long- term efficacy of RFH therapy versus SSG in the treatment of CL in patients residing in Leishmania endemic regions. We propose to perform this trial in India, Ethiopia, Peru and Guatemala because infections in these regions are caused by different Leishmania species, and they represent clinically diverse forms of CL. This R34 application will allow us to select study team members, identify enrollment sites and local laboratories, and obtain approvals from local regulators and Institutional Review Boards (Aim 1), and to finalize the clinical trial protocol including a statistical analysis plan, data management and safety monitoring plans, and informed consent process and documents (Aim 2). Accomplishing these aims will lay a sound foundation for our multicenter clinical trial.
Cutaneous leishmaniasis is caused by Leishmania parasites. This infection is a global health problem and a neglected tropical disease. This disease has also affected several US Army personnel serving in Iraq and Afghanistan as well as canine populations in the US. Current treatment of CL involves 20 injections of pentavalent antimonial drugs which are toxic and have poor patient compliance. The goal of this proposal is to plan a Phase III open label multicenter clinical trial to compare long-term efficacies of conventional antimonial injection treatment versus a single topical RF-induced heat therapy in treatment of CL in patients living in Leishmania endemic regions of India, Peru, Guatemala and Ethiopia.
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