Treating cutaneous leishmaniasis by radio-frequency induced heat (RFH) therapy

通过射频诱导热 (RFH) 疗法治疗皮肤利什曼病

• 批准号: 8331827
• 负责人: Abhay R Satoskar
• 金额: $ 22.88万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-10 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8331827
• 关键词: Affect; Afghanistan; Aftercare; Antimony; Applications Grants; Army Personnel; Burn injury; Canis familiaris; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Clinical trial protocol document; Country; Cutaneous; Cutaneous Leishmaniasis; Data; Dermis; Disease; Enrollment; Ethiopia; Follow-Up Studies; Foundations; Frequencies; Goals; Guatemala; HIV; Heating; Human Resources; Immune system; Immunocompetent; Immunocompromised Host; India; Individual; Infection; Informed Consent; Injection of therapeutic agent; Institutional Review Boards; Intralesional Injections; Intramuscular Injections; Iraq; Laboratories; Leishmania; Leishmaniasis; Lesion; Life; Local anesthesia; Monitor; Parasites; Patient Selection; Patients; Peru; Pharmaceutical Preparations; Phase; Phase III Clinical Trials; Population; Process; Radio; Recurrence; Refractory; Relapse; Safety; Safety Management; Selection Criteria; Site; Sodium; Soldier; Stibogluconate Sodium; T-Lymphocyte; Therapeutic heat application; Tissues; Tropical Disease; Visceral Leishmaniasis; authority; compliance behavior; data management; database design; disorder later incidence prevention; disorder risk; follow-up; global health; interest; intravenous injection; member; neglect; novel; open label; prevent; radiofrequency; sound

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: 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.

描述（由申请人提供）：利什曼原虫属原生动物寄生虫引起的感染包括皮肤利什曼病（CL）、粘膜利什曼病（ML）和内脏利什曼病（VL）。目前有超过1200万人患有利什曼病，每年约有200万新发病例，使其成为全球主要健康问题。最近，美国的犬类以及在伊拉克和阿富汗服役的军队人员中都发现了 CL。全身性五价锑剂如葡萄糖酸锑钠 (SSG) 是全世界推荐的 CL 治疗方法，但它们具有毒性，且治疗依从性较差，因为需要每天注射 3 周或更长时间。此外，在免疫功能低下的个体中，锑治疗与复发有关。我们对安全、易于管理且能有效诱导长期治愈的新疗法感兴趣。最近，射频诱导热（RFH）疗法已被用于治疗 CL。这种治疗在局部麻醉下将受控的局部射频传送到病变部位，持续 30-60 秒。几项短期随访（4-5 个月）研究和一项长期随访（12 个月）研究涉及在伊拉克感染 L. Major 的美国士兵，发现 RFH 疗法相当，甚至更好，优于全身锑治疗。我们最近发现，对于 SSG 难治的 HIV 感染患者，RFH 疗法也能有效诱导 CL 治愈。此外，我们发现 RFH 疗法在 6 个月内使近 98% 的免疫功能正常的 CL 患者完全临床治愈，并且长达 1 年没有复发。这些发现表明，RFH 疗法应该能有效诱导免疫功能正常和免疫功能低下患者的 CL 长期治愈，因此可能代表一种新的一线治疗方法。然而，需要进行临床试验来确定治愈率并建立 RFH 疗法治疗由其他利什曼原虫物种引起的常规药物难以治疗的 CL 的长期疗效，并确定疾病复发的风险（如果有）生活在利什曼原虫流行地区的患者。该 R34 申请的目标是计划一项开放标签 III 期临床试验，以比较长期效果 RFH 疗法与 SSG 治疗居住在利什曼原虫流行地区的 CL 患者的疗效。我们建议在印度、埃塞俄比亚、秘鲁和危地马拉进行这项试验，因为这些地区的感染是由不同的利什曼原虫物种引起的，并且它们代表了临床上不同形式的 CL。该 R34 申请将使我们能够选择研究团队成员，确定招募地点和当地实验室，并获得当地监管机构和机构审查委员会的批准（目标 1），并最终确定临床试验方案，包括统计分析计划、数据管理和安全监测计划以及知情同意流程和文件（目标 2）。实现这些目标将为我们的多中心临床试验奠定良好的基础。 公共卫生相关性：皮肤利什曼病是由利什曼原虫寄生虫引起的。这种感染是一个全球性的健康问题，也是一种被忽视的热带疾病。这种疾病还影响了在伊拉克和阿富汗服役的几名美国陆军人员以及美国的犬类种群。目前CL的治疗需要注射20次五价锑药物，这些药物有毒且患者依从性差。该提案的目标是计划一项 III 期开放标签多中心临床试验，以比较传统锑注射治疗与单次局部射频诱导热疗治疗生活在印度利什曼原虫流行地区的 CL 患者的长期疗效，秘鲁、危地马拉和埃塞俄比亚。