Hyperthermia Combined With Hydrogen Peroxide Microneedle Patch for Viral Warts

A Randomized, Parallel-Group, Controlled, Assessor-Blinded Clinical Trial of Hyperthermia Combined With Hydrogen Peroxide Microneedle Patch for Viral Warts

Hyperthermia treatment (hyperthermia) refers to treating diseases with temperature (39-45 ° C) beyond normal body temperature,. It has been reported that local warming at 44 ° C is able to effectively mobilize the body's immunity and clear HPV infected lesions, such as condyloma acuminatum and verruca vulgaris, etc. Significant progress has been made in the application of hyperthermia for viral skin diseases. Clinically, the addition of hydrogen peroxide solution can enhance the efficacy of hyperthermia in treating HPV infection. As a common transdermal drug delivery method, microneedles can increase drug penetration and thereby further improve treatment outcomes. Based on these findings, this study aims to explore an adjunctive approach to hyperthermia for treating viral warts to further enhance therapeutic efficacy.

This study employs a randomized, parallel-group, assessor-blinded design. Participants will be randomly assigned to three groups: hyperthermia alone, hyperthermia combined with microneedle patch (loaded with 0.9% saline), and hyperthermia combined with hydrogen peroxide microneedle patch (experimental group). An adaptive design will be adopted. The sample size is estimated at 70 participants per group, accounting for a potential 20% dropout rate. Interim analyses will be conducted during follow-up, and enrollment will be stopped when a positive result is reached for the primary efficacy endpoint (cure rate), at which point the sample size will be adjusted accordingly.

Study Overview

• Status: Recruiting
• Conditions: Warts
• Intervention / Treatment: Drug: 0.9 % saline; Device: Hyperthermia at 44℃; Device: Microneedle patch; Drug: 3% hydrogen peroxide solution

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hao Guo; Phone Number: +86 13840365892; Email: guohao27@126.com

Study Locations

• China
  • Shenyang, China
    • Recruiting
    • Infrared Hyperthermia Device
    • Contact: Hao Guo; Phone Number: +86 13840365892; Email: guohao27@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 6-65 years, male or female;
2. Clinically diagnosed with common warts, palmar/plantar/digital warts (≥1 lesion), with a Physician's Wart Assessment score ≥2 (0: no visible wart, no further treatment required; 1: visible wart, diameter <3 mm; 2: single wart diameter ≥3 mm and <6 mm; 3: single wart diameter ≥6 mm);
3. The subject or legal guardian is able to understand and sign the informed consent form and agrees to participate in the study.

Exclusion Criteria:

1. Subjects presenting with atypical warts clinically;
2. Subjects with immune dysfunction or autoimmune diseases;
3. Pregnant or breastfeeding women;
4. Subjects who have received human papillomavirus (HPV) vaccination within the past 6 months;
5. Subjects who have undergone the following systemic treatments within the specified time frames: immunomodulators/immunosuppressants (e.g., etanercept), within 4 months; corticosteroids (inhaled and intranasal use permitted), within 1 month;
6. Subjects who have received the following treatments on or around the warts within the specified time frames: laser or other photochemical therapies (intense pulsed light, photodynamic therapy), within 3 months; immunotherapy (candida antigen), within 4 months; cryotherapy with liquid nitrogen, within 2 months; hydrogen peroxide, within 3 months; antimetabolite therapy (5-fluorouracil), within 2 months; retinoids, within 3 months;
7. Subjects with a history of the following diseases prior to enrollment: skin malignancy within the past 6 months, premalignant skin conditions (actinic keratosis) within the past 6 months, or currently in the acute progressive phase of skin or systemic diseases (e.g., psoriasis, atopic dermatitis, eczema, sun damage, etc.) or presenting with conditions (such as sunburn, open wounds) that may increase the risk of participation or interfere with evaluation;
8. Subjects with diseases affecting skin healing, such as diabetes mellitus, vitamin A deficiency, etc.;
9. Subjects with cold-sensitive conditions such as cryoglobulinemia or cold urticaria that may lead to abnormal observation results;
10. Subjects with severe dysfunction of the heart, lung, liver, kidney, hematopoietic system, or other vital organs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hyperthermia at 44°C; Sterile cotton soaked in normal saline was applied to cover each wart, followed by occlusion with plastic film for one hour, once daily, for six consecutive weeks. One wart was selected to receive 44 °C hyperthermia for 30 minutes per session: three consecutive sessions in the first week, two sessions in the second week, and two sessions in the third week. Hyperthermia was administered immediately after occlusion, during which the wart was rinsed with normal saline and gently dried with a sterile cotton swab before the start of hyperthermia.	Drug: 0.9 % saline; Dressing: Like the Local Hyperthermia Group, use a microneedle patch loaded with 0.9% saline. Irradiation: For seven sessions in three weeks, use simulated infrared light (without heat) with the same frequency as the Local Hyperthermia Group. Local Hyperthermia treats the target warts(largest and most severe warts), while medication addresses all warts.; Device: Hyperthermia at 44℃; The infrared hyperthermia device was used as follows: based on the thermal tolerance of different body surface areas, the surface temperature was set to 44 °C ± 1 °C. The lesion was disinfected with alcohol. After the skin had dried, the patient's most painful or largest wart was selected as the target lesion and treated with 44 °C hyperthermia. The treatment was administered for three consecutive days (sessions), each lasting 30 minutes. After an interval of 7-10 days, the same target lesion received two consecutive days (sessions) of treatment, followed by one session every 7-10 days thereafter. For patients with multiple lesions, only one target lesion was treated using the above protocol, while the remaining lesions received no intervention.
Experimental: Hyperthermia combined with microneedle patch (loaded with 0.9% saline); One wart was selected to receive 44 °C hyperthermia for 30 minutes per session: three consecutive sessions in the first week, two sessions in the second week, and two sessions in the third week. A microneedle patch loaded with 0.9% saline was applied to the target lesion daily for one hour per day, for a total of six weeks.	Drug: 0.9 % saline; Dressing: Like the Local Hyperthermia Group, use a microneedle patch loaded with 0.9% saline. Irradiation: For seven sessions in three weeks, use simulated infrared light (without heat) with the same frequency as the Local Hyperthermia Group. Local Hyperthermia treats the target warts(largest and most severe warts), while medication addresses all warts.; Device: Hyperthermia at 44℃; The infrared hyperthermia device was used as follows: based on the thermal tolerance of different body surface areas, the surface temperature was set to 44 °C ± 1 °C. The lesion was disinfected with alcohol. After the skin had dried, the patient's most painful or largest wart was selected as the target lesion and treated with 44 °C hyperthermia. The treatment was administered for three consecutive days (sessions), each lasting 30 minutes. After an interval of 7-10 days, the same target lesion received two consecutive days (sessions) of treatment, followed by one session every 7-10 days thereafter. For patients with multiple lesions, only one target lesion was treated using the above protocol, while the remaining lesions received no intervention.; Device: Microneedle patch; Purpose: To facilitate drug loading. Instructions:Add an appropriate amount of 3% hydrogen peroxide solution or 0.9% sodium chloride solution into the corresponding chamber. Apply the microneedle patch to the wart and secure it with tape. Press the raised part of the aluminum film sequentially with fingers until the chamber fully collapses and makes contact with the skin. After one hour of contact, dispose of the patch in a medical waste container.
Experimental: Hyperthermia combined with hydrogen peroxide microneedle patch; One wart was selected to receive 44 °C hyperthermia for 30 minutes per session: three consecutive sessions in the first week, two sessions in the second week, and two sessions in the third week. A hydrogen peroxide microneedle patch was applied to the target lesion daily for one hour per day, for a total of six weeks.	Device: Hyperthermia at 44℃; The infrared hyperthermia device was used as follows: based on the thermal tolerance of different body surface areas, the surface temperature was set to 44 °C ± 1 °C. The lesion was disinfected with alcohol. After the skin had dried, the patient's most painful or largest wart was selected as the target lesion and treated with 44 °C hyperthermia. The treatment was administered for three consecutive days (sessions), each lasting 30 minutes. After an interval of 7-10 days, the same target lesion received two consecutive days (sessions) of treatment, followed by one session every 7-10 days thereafter. For patients with multiple lesions, only one target lesion was treated using the above protocol, while the remaining lesions received no intervention.; Device: Microneedle patch; Purpose: To facilitate drug loading. Instructions:Add an appropriate amount of 3% hydrogen peroxide solution or 0.9% sodium chloride solution into the corresponding chamber. Apply the microneedle patch to the wart and secure it with tape. Press the raised part of the aluminum film sequentially with fingers until the chamber fully collapses and makes contact with the skin. After one hour of contact, dispose of the patch in a medical waste container.; Drug: 3% hydrogen peroxide solution; Dressing: Like the Local Hyperthermia Group, use a microneedle patch loaded with 3% hydrogen peroxide . Irradiation: For seven sessions in three weeks, use simulated infrared light (without heat) with the same frequency as the Local Hyperthermia Group. Local Hyperthermia treats the target warts(largest and most severe warts), while medication addresses all warts.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clearance rate of warts	The complete clearance rate was defined as the proportion of patients with lesions that completely disappeared within 6 months of completing all treatments.	6 months after the first time of treatment.
Time to complete clearance	Median duration from first treatment to complete resolution (days)	6 months after the first time of treatment.
Recurrence rate of warts	Complete clearance was defined as the proportion of patients with complete disappearance of lesions within 6 months of completion of all treatments, and recurrence was the proportion of patients with recurrence of lesions at the cured lesion site within 6 and 12 months after treatment.	Recurrence was the proportion of patients with reappearance of lesions at previously cleared sites within 6 months after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related pain intensity	Pain assessed by Visual Analog Scale (VAS) ranging from 0 (no pain) to 10 (worst imaginable pain)	During each treatment session (Day 1, 2, 3, 10, 11, 18, 19)
Changes in the size and number of warts at different points in time		At months 1, 3, and 6
Occurrence of adverse events	Occurrence of adverse events (short - and long-term adverse reactions) (e.g. blisters, erythema, nail changes, ulcers/scars, hyperpigmentation, hypopigmentation, erosion)	During treatment and follow-up
Time to first wart clearance		At months 1, 3, and 6

Collaborators and Investigators

• Sponsor: First Hospital of China Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 10, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases; DNA Virus Infections; Skin Diseases; Skin Diseases, Infectious; Tumor Virus Infections; Skin Diseases, Viral; Papillomavirus Infections; Skin and Connective Tissue Diseases; Warts; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: 【2025】770

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