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

NCT ID: NCT05300009

Last Updated: 2022-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

68 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-15

Study Completion Date

2023-08-15

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.

Conditions

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Warts

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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topical methotrexate hydrogel 1% coupled with microneedling

patients who will receive topical methotrexate hydrogel 1% coupled with microneedling

Group Type EXPERIMENTAL

topical methotrexate hydrogel 1% coupled with microneedling.

Intervention Type COMBINATION_PRODUCT

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.

cryotherapy

patients who will receive cryotherapy

Group Type ACTIVE_COMPARATOR

Liquid nitrogen

Intervention Type OTHER

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.

Interventions

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topical methotrexate hydrogel 1% coupled with microneedling.

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.

Intervention Type COMBINATION_PRODUCT

Liquid nitrogen

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.

Intervention Type OTHER

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 .
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Assiut University

OTHER

Sponsor Role lead

Responsible Party

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Khulood Fadhl Ahmed Alhakami

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Khulood F Alhakami, M.B.B.CH

Role: PRINCIPAL_INVESTIGATOR

Assiut University

Central Contacts

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Eman R Mohamed, Professor

Role: CONTACT

+201005298992

Heba H Sayed, Lecturer

Role: CONTACT

+201002866919

References

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Ghittoni R, Accardi R, Chiocca S, Tommasino M. Role of human papillomaviruses in carcinogenesis. Ecancermedicalscience. 2015 Apr 29;9:526. doi: 10.3332/ecancer.2015.526. eCollection 2015.

Reference Type BACKGROUND
PMID: 25987895 (View on PubMed)

Kimura U, Takeuchi K, Kinoshita A, Takamori K, Suga Y. Long-pulsed 1064-nm neodymium:yttrium-aluminum-garnet laser treatment for refractory warts on hands and feet. J Dermatol. 2014 Mar;41(3):252-7. doi: 10.1111/1346-8138.12411. Epub 2014 Feb 10.

Reference Type BACKGROUND
PMID: 24506821 (View on PubMed)

Shaheen MA, Salem SA, Fouad DA, El-Fatah AA. Intralesional tuberculin (PPD) versus measles, mumps, rubella (MMR) vaccine in treatment of multiple warts: a comparative clinical and immunological study. Dermatol Ther. 2015 Jul-Aug;28(4):194-200. doi: 10.1111/dth.12230. Epub 2015 Apr 6.

Reference Type BACKGROUND
PMID: 25847793 (View on PubMed)

Sung JY, Hong JH, Kang HS, Choi I, Lim SD, Lee JK, Seok JH, Lee JH, Hur GM. Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis. Immunopharmacology. 2000 Apr;47(1):35-44. doi: 10.1016/s0162-3109(99)00185-x.

Reference Type BACKGROUND
PMID: 10708808 (View on PubMed)

Cipriani P, Ruscitti P, Carubbi F, Liakouli V, Giacomelli R. Methotrexate: an old new drug in autoimmune disease. Expert Rev Clin Immunol. 2014 Nov;10(11):1519-30. doi: 10.1586/1744666X.2014.962996. Epub 2014 Sep 22.

Reference Type BACKGROUND
PMID: 25245537 (View on PubMed)

Beck S, Zhu Z, Oliveira MF, Smith DM, Rich JN, Bernatchez JA, Siqueira-Neto JL. Mechanism of Action of Methotrexate Against Zika Virus. Viruses. 2019 Apr 10;11(4):338. doi: 10.3390/v11040338.

Reference Type BACKGROUND
PMID: 30974762 (View on PubMed)

Duarte AA, Carneiro GP, Murari CM, Jesus LCB. Nail psoriasis treated with intralesional methotrexate infiltration. An Bras Dermatol. 2019 Oct 17;94(4):491-492. doi: 10.1590/abd1806-4841.20198170. eCollection 2019. No abstract available.

Reference Type BACKGROUND
PMID: 31644634 (View on PubMed)

Sutton L, Swinehart JM, Cato A, Kaplan AS. A clinical study to determine the efficacy and safety of 1% methotrexate/Azone (MAZ) gel applied topically once daily in patients with psoriasis vulgaris. Int J Dermatol. 2001 Jul;40(7):464-7. doi: 10.1046/j.1365-4362.2001.01244.x. No abstract available.

Reference Type BACKGROUND
PMID: 11679005 (View on PubMed)

Abdo HM, Elrewiny EM, Elkholy MS, Ibrahim SM. Efficacy of intralesional methotrexate in the treatment of plantar warts. Dermatol Ther. 2020 Mar;33(2):e13228. doi: 10.1111/dth.13228. Epub 2020 Jan 29.

Reference Type BACKGROUND
PMID: 31965678 (View on PubMed)

Dehshahri A, Kumar A, Madamsetty VS, Uzieliene I, Tavakol S, Azedi F, Fekri HS, Zarrabi A, Mohammadinejad R, Thakur VK. New Horizons in Hydrogels for Methotrexate Delivery. Gels. 2020 Dec 30;7(1):2. doi: 10.3390/gels7010002.

Reference Type BACKGROUND
PMID: 33396629 (View on PubMed)

Badran MM, Kuntsche J, Fahr A. Skin penetration enhancement by a microneedle device (Dermaroller) in vitro: dependency on needle size and applied formulation. Eur J Pharm Sci. 2009 Mar 2;36(4-5):511-23. doi: 10.1016/j.ejps.2008.12.008. Epub 2008 Dec 25.

Reference Type BACKGROUND
PMID: 19146954 (View on PubMed)

Ita K. Dissolving microneedles for transdermal drug delivery: Advances and challenges. Biomed Pharmacother. 2017 Sep;93:1116-1127. doi: 10.1016/j.biopha.2017.07.019. Epub 2017 Jul 19.

Reference Type BACKGROUND
PMID: 28738520 (View on PubMed)

Other Identifiers

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MGMW

Identifier Type: -

Identifier Source: org_study_id

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