Antifungal Agents and Infrared Thermotherapy Alone or in Combination in the Treatment of Sporotrichosis

Официальное название

A Randomized Controlled Clinical Trial of Antifungal Agents and Infrared Thermotherapy Alone or in Combination in the Treatment of Sporotrichosis

Обзор

Sporotrichosis is a chronic granulomatous mycosis caused by sporothrix complex. The course of sporotrichosis is always prolonged and even life-threatening, the treatment of this disease in an important scientific problem to be solved. The investigators previously found the predominance of subtype M2 macrophage which play an anti-inflammatory role in the lesions of sporotrichosis, the predominance of M2 macrophage may be responsible for the persistence of sporotrichosis; the investigators also found that local hyperthermia is effective in the treatment of sporotrichosis and hyperthermia treatment can activate the CRAC calcium channel in macrophages which triggers pro-inflammatory type M1 polarization and subsequent killing of sporothrix, however, the mechanism still calls for further investigation. The investigators hypothesize that hyperthermia leads to the activation of CRAC channels resulting in profound Ca2+ influx and Ca2+ upregulates NLRP3 inflammasome expression through inducing Nrf2 activation, then NLRP3 overexpression triggers M1 polarization and subsequent killing of sporothrix. Furthermore, the activation of Nrf2 upregulates STIM1 expression which forms a positive feedback for M1 type polarization of macrophages and further subsequent killing of sporothrix. The purpose of this project is to identify the hypothesis that hyperthermia could treat sporotrichosis by promoting pro-inflammatory type M1 polarization in macrophages, the mechanism by which hyperthermia could treat sporotrichosis is local hyperthermia could led to STIM1/CRAC calcium channel activation mediated calcium ions/Nrf2/NLRP3 induced M1 macrophages polarization and subsequent killing of sporothrix. The hypothesis will be identified at the cellular level, at the animal model level and at the clinical specimens level. The investigators believe that the project will guide the application of hyperthermia in the treatment of sporotrichosis and provide a new basis of theory and practice after the investigators achieving these goals.

Вмешательства

• Препарат Itraconazole
  oral itraconazole (children less than 15 years old 6 mg/kg/d; adult patients: 200 mg/d) for a total course of 3-6 months
• Устройство Infrared thermotherapy apparatus
  infrared hyperthermia device for 3 consecutive days (times / day), each treatment for 30 minutes After two weeks (14 days), the lesions of the same target were treated continuously for 2 days (times per day), and then once a week for 2 consecutive times, the method was the same as before. After 7 times of treatment, the study physician decided whether to continue treatment n times after 1-2 weeks (n ≥ 0) according to the recovery of the subjects.
• Другое Itraconazole and Infrared thermotherapy apparatus
  oral itraconazole (children less than 15 years old 6 mg/kg/d; adult patients: 200 mg/d) for a total course of 3-6 months, while infrared hyperthermia device for 3 consecutive days (times / day), each treatment for 30 minutes After two weeks (14 days), the lesions of the same target were treated continuously for 2 days (times per day), and then once a week for 2 consecutive times, the method was the same as before. After 7 times of treatment, the study physician decided whether to continue treatm

Первичные конечные точки

• the overall clinical clearance rate of skin lesions [Срок оценки: Three months]

Вторичные конечные точки (4)

• Overall clinical clearance rate and recurrence rate [Срок оценки: Six months]
• adverse reactions and incidence [Срок оценки: Six months]
• the clearance rate of target skin lesions [Срок оценки: Three months]
• overall lesion clearance rate [Срок оценки: Three months]

Критерии участия

Критерии включения

• The results of pathology and fungal culture were all patients with sporotrichosis.
• Informed consent to the purpose and content of the study, and follow-up as required
• The physical condition and self-condition can cooperate with the treatment.

Критерии исключения

• Subjects who are unable to maintain a relatively stable posture during treatment.
• Those who are sensitive or allergic to this experimental drug.
• Systemic antifungal or KI therapy within 12 months
• Local antifungal therapy within 1 month.
• Previous history of immunodeficiency virus (HIV) infection, or positive HIV antibody in screening period.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• First Hospital of China Medical University — Шэньян

Идентификаторы

NCT: NCT06300138 · 2023-631-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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