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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sporotrichosis
• Intervention / Treatment: Other: Itraconazole and Infrared thermotherapy apparatus; Drug: Itraconazole; Device: Infrared thermotherapy apparatus

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhengxiu Li, Doctor; Phone Number: 024-83282524; Email: lizx_cmu@foxmail.com

Study Locations

• China
  • Shenyang, China
    • Recruiting
    • First Hospital of China Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug combined with infrared hyperthermia group; 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 treatment n times after 1-2 weeks (n ≥ 0) according to the recovery of the subjects.	Other: 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 treatment n times after 1-2 weeks (n ≥ 0) according to the recovery of the subjects.
Experimental: Drug group; Itraconazole (6 mg/kg/d; for children less than 15 years old, 200 mg/d for adults) was taken orally for 3-6 months. The specific course of treatment was determined by the research physician according to the recovery of the subjects.	Drug: 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
Experimental: Infrared hyperthermia group; 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.	Device: 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.; Other Names: YY-WRY-V01 Infrared thermotherapy apparatus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the overall clinical clearance rate of skin lesions	Three months after treatment, the overall clinical clearance rate of skin lesions in the three groups.	Three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall clinical clearance rate and recurrence rate	Overall clinical clearance rate and recurrence rate of skin lesions in three groups	Six months
adverse reactions and incidence	adverse reactions and incidence in three groups	Six months
the clearance rate of target skin lesions	Three months after treatment, the clearance rate of target skin lesions in hyperthermia treatment group and hyperthermia combined with antifungal therapy group.	Three months
overall lesion clearance rate	In patients with multiple lesions, the overall lesion clearance rate was 3 months after treatment.	Three months

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 29, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Sporotrichosis; local hyperthermia
• Additional Relevant MeSH Terms: Infections; Skin Diseases; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Mycoses; Dermatomycoses; Sporotrichosis; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP3A Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Hydroxyitraconazole
• Other Study ID Numbers: 2023-631-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No