Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts

Study Overview
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Brief Summary
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To study the clinical efficacy of the topically applied MTX hydrogel preparation combined with microneedling to increase drug delivery and efficacy in comparison with cryotherapy in treatment of warts.

Detailed Description
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Warts are benign proliferation of skin and mucosa caused by the human papilloma virus (HPV). Currently, over 170 HPV types have been identified. Certain HPV types tend to infect skin at anatomical sites, for an example, palmoplantar warts are usually caused by Serotypes 1, 2, and 4; however, warts of any HPV type may occur at any site. Warts are transmitted by direct or indirect contact, and predisposing factors include disruption to the normal epithelial barrier. There are several modalities for treatment of warts including cryotherapy, electrocoagulation, topical salicylic acid, topical 5-fluorouracil, and laser surgery. All these treatment options can be painful, time-consuming, and/or expensive, and none is considered the gold standard. Treatments for warts have also included intralesional injections of tuberculin purified protein derivative (PPD), measles, mumps, and rubella vaccine (MMR), and Candida albicans antigen (candidin). This treatment approach is known as intralesional immunotherapy as it is thought that these modalities activate the immune system to recognize the virus, leading to wart clearance . MTX as an antimetabolite and antifolate drug is a time-tested effective treatment extensively used orally or parenteral in various autoimmune disorders like psoriasis, psoriatic arthritis, alopecia areata, lupus erythematosus, and rheumatoid arthritis in low to moderate doses with good efficacy, safety, and tolerability on a long-term basis MTX is appropriate for rapidly growing tumors since it inhibits DNA synthesis in actively dividing cells. MTX is a folic acid analog that binds to the dihydrofolate reductase, blocking the formation of tetrahydrofolate and preventing the synthesis of the purine nucleotide thymidine . Antiviral effect of MTX was observed in the treatment of Zika virus infected cells explaining the antiviral effect of MTX through inhibition of dihydrofolate reductase .. A literature review shows that intralesional MTX has been successfully used for several indications with no complications reported. Unlike systemic MXT, topical preparations of the drug, that was adapted for the treatment of localized lesions, showed nonsignificant related hepatotoxic and hematologic adverse effects . Previous studies used intralesional MTX injection in the treatment of viral warts with different concentrations and revealed that intralesional MTX was less effective in treating plantar warts . Since MTX is used for various diseases via different routes of administration, the development of novel drug delivery systems to improve its pharmacokinetic properties and targetability is a necessary step for future investigations . Controlling the burst release and the introduction of new routes of administration would be possible if the drug could be formulated using different delivery systems. Among various drug delivery systems proposed for MTX delivery, great attention has been directed to hydrogels due to their unique and attractive characteristics . Microneedling is a fine needle that penetrates the skin to induce micro-injuries leading to production of collagen fibers and release of growth factors . Microneedling has been used as an adjuvant therapy helping a drug delivery and also used in treatment of various dermatologic diseases . In this study, the investigators chose the hydrogel formulation at a concentration of 1%w/v as a topical MTX form coupled with microneedling to increase the efficacy of methotrexate in treatment of warts. Hydrogel used will be optimized for biocompatibility, consistency and chemical compatibility with methotrexate.

Official Title
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Efficacy and Safety of Topical Methotrexate Gel 1% Coupled With Microneedling in Treatment of Warts : A Prospective Controlled Randomized Trial

Conditions
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Warts

Intervention / Treatment
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* Combination Product: topical methotrexate hydrogel 1% coupled with microneedling.
* Other: Liquid nitrogen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than 18 years up to 60 years old. Patients with plantar or common warts. Exclusion Criteria: pregnancy and lactation immunosuppression or being under any kind of treatment causing absolute or relative immunosuppression. history of any bleeding, clotting disorder or using anticoagulants. chronic systemic diseases such as chronic renal failure, hepatic insufficiency, and cardiovascular disorders. concurrent use of systemic or topical treatments of warts .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: topical methotrexate hydrogel 1% coupled with microneedling<br>patients who will receive topical methotrexate hydrogel 1% coupled with microneedling | Combination Product: topical methotrexate hydrogel 1% coupled with microneedling.<br>* Microneedling will be performed on each wart for a maximum 5 lesions per patient using dermapen (Ostar rechargeable dermapen, OB-DG 03N, Ostar Beauty Sci-Tech Co, Beijing, China) supplied with 12 needles arranged in rows. The penetration depth was adjusted at 2-mm, endpoint was pinpoint bleeding and the dermapen will be held by the hand in a vertical direction on the wart. Then topical methotrexate 1% gel will be applied on the lesions every session.<br>|
| Active Comparator: cryotherapy<br>patients who will receive cryotherapy | Other: Liquid nitrogen<br>* The wart is frozen for 10 to 30 seconds until a 1- to 2-mm ice ball halo surrounds the targeted area. The sessions were performed every 2 week until complete clearance for a maximum of six sessions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete resolution of all treated wart(s). | Proportion of participants with total remission of wart(s) at the end of the intervention in the two arms of the clinical trial assessed by the investigator and photographic evaluation . Complete response: responders who show 100% improvement (disappearance of all warts and return to normal skin markings). | 8 weeks | 
| Partial resolution | Number of subjects achieving partial resolution of treated wart(s) at the end of the intervention in the two arms of the clinical trial assessed by the investigator, photographic evaluation and The following grading system : Marked response: responders who show 76 to 99% decrease in number and/or decrease in apparent size, as assessed by a clinician and photographic evaluation also known as near-complete response. Moderate response: partial responders show 25 to 75% improvement. No or minimal response: less than 25% decrease in size/numbers of all warts. the stud | 8 weeks | 
| Incidence of adverse events | Proportion of participants that developed a serious side effect in the two arms during the clinical trial. | 8 weeks |