Efficacy and Safety of Platelet-rich Plasma, Metformin and Cryotherapy in Treatment of Non-genital Warts

November 14, 2024 updated by: Aya Gamal Abd El-Wahab Mahmoud, Assiut University
  1. Evaluation of the efficacy and safety of intralesional injection of autologous platelet-rich plasma in treatment of various types of cutaneous non genital warts
  2. Evaluation of the efficacy and safety of intralesional injection of metformin in treatment of various types of cutaneous non genital warts
  3. Comparing the efficacy and safety of intralesional injection of autologous platelet-rich plasma and intralesional injection of metformin with that of cryocautery in treatment of various types of cutaneous non genital warts.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Cutaneous warts caused by human papillomavirus (HPV) are benign proliferative lesions that occur at any age in human life.

More than 100 different types of HPVs have been fully characterized . Warts may exist in different forms according to the epithelial surface affected and HPV type responsible for the infection. Common warts (Verruca vulgaris), plantar warts (Verruca plantaris), flat or plane warts (Verruca plana) and genital warts (Condyloma acuminata) are some of the clinical manifestations of HPV infection .

Although lesions can resolve spontaneously within 2 years without treatment, treatment is sought by many who are unwilling to wait for spontaneous clearance, by those who do not experience such resolution and for reasons of preventing infections of other individuals and reducing the risk of malignancy . Additionally, pain, discomfort, recurrent bleeding, functional limitation, and esthetic disfigurements due to cutaneous warts are common indications for seeking treatment.

Several therapeutic modalities have been used to treat HPV infections. The choice of treatment should take into account factors such as age, location, number and size of the lesions, clinical subtype and the patient's immunological status.

Available treatments are aimed at either breakdown or removal of visible warts or induction of cytotoxicity against infected cells .

They include destructive agents (keratolytic, cryotherapy, curettage and cautery, laser, photodynamic therapy), antimitotic agents (podophyllin, bleomycin, retinoids), immune stimulants (topical sensitizers, cimetidine), and topical virucidal agents [formaldehyde (formalin), glutaraldehyde (Glutaral) .

Unfortunately, no single treatment is satisfactory for all patients. Many treatments are time consuming, painful and can leave scars or hypopigmentation; moreover, recurrence rates after any treatment range from 6% to 100% . So, the development of new effective and safe treatments seems to be an urgent need.

Cryocautery represents a first line of therapy for cutaneous warts. It uses liquid nitrogen to freeze tissues and destroy warts.

Liquid nitrogen cryotherapy involves freezing a wart with liquid nitrogen for 10 to 20 seconds every two to three weeks. Precisely how cryotherapy destroys warts is not well understood, but the prevailing theory is that freezing causes local irritation, leading the host to mount an immune reaction against the virus.

However, side effects for cryocautery are common, they include pain, depigmentation, delayed healing, ulceration, scar formation and recurrence

Platelet- rich plasma (PRP) is a small volume of plasma rich in platelets. It has become a hopeful therapy in the last decade to treat several cutaneous diseases due to its increased concentrations of growth factors. As it is of autologous origin, it reduces the possibility of adverse effects and transfusion transmitted infections.

PRP has been utilized in the treatment of numerous cutaneous diseases such as alopecia, skin ulcers, and acne vulgaris. Its utility has been extended to other cutaneous diseases as melasma, hyperpigmentation, and burns, in addition to its usefulness in tissue repair and regeneration.

To the best of our knowledge the efficacy of PRP in the treatment of plane warts was assessed in a single uncontrolled clinical trial which revealed that intralesional injection of PRP was effective and well-tolerated immunotherapy for treating of multiple recalcitrant plane warts.

Moreover, complete remission of multiple resistant plantar warts after treatment by combined intralesional autologous PRP injections and local application of salicylic acid 30% was observed in only one case report.

Mechanisms suggested for such promising response of warts to intralesional injection of PRP included induction of expression of numerous pro-inflammatory cytokines as interleukin-6, interleukin-8, tumor necrosis factor-alpha, and C-C motif chemokine ligand 5 which then activate several immune cells leading to increased inflammation.

Also, platelets expressed CD40L, on its activation; it modulates its interaction with CD40 presenting on macrophages, B-cells, monocytes, endothelial cells, dendritic cells, and mediates their activities.

Platelets may modulate the innate immunity and provide antimicrobial activities either by synthesis of antimicrobial peptides or by modulating the immune activities of other immune cells as neutrophils and monocytes.

These interesting findings open the way for future studies to evaluate the usefulness of PRP in treating different clinical types of warts.

Metformin, a widely used drug to treat type 2 diabetes mellitus and metabolic syndrome, has been used systemically in different dermatological diseases such as hormonal acne, hidradenitis suppurativa (HS) and acanthosis nigricans in which it may act through improving hyperinsulinemia . Additionally, it was found effective when used topically in treatment of melasma with an equivalent effect to triple combination cream , and acne vulgaris .

Metformin has immunomodulatory activity that reduces the production of proinflammatory cytokines, it also inhibits the cytokine production of pathogenic Th1 and Th17 cells .

Furthermore, many studies, both in vitro and in vivo with small animal models, have highlighted the antiviral properties of metformin.

Additionally, Metformin has shown antitumorigenic potential in HPV-positive cancer cells. Such properties suggests that metformin might be effective therapeutic option for viral warts. However, to the best of our knowledge, no studies have been conducted to explore that hypothesis.

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Patients with cutaneous (extragenital) viral warts (single , new or recurrent, common, plane and/or planter warts.
  • Age ranged from 8 to 60 years old.
  • No concurrent systemic or topical treatment of warts.

Exclusion Criteria:

  • Patients with fever or signs of any inflammation or infection
  • 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 diabetes, chronic renal failure, hepatic insufficiency, and cardiovascular disorders.
  • atients using concurrent treatments for warts or one month before .
  • Any generalized dermatitis, allergic skin disorders

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intralesional injection of Metformin
Group 1: will include 36 patients with multiple common, plantar and/or plane warts. They will be treated by intralesional injection of metformin using insulin syringe every 2-weeks until complete clearance or for a maximum of 6 sessions.
Drug: Metformin
platelet-rich plasma, metformin and cryotherapy in treatment of non-genital warts
Experimental: Intralesional injection of platelet- rich plasma
Group 2: will include 36 patients with multiple common, plantar and/or plane warts. They will be treated by intralesional injection of platelet- rich plasma into the warts by an insulin syringe every 2 weeks until complete clearance or for a maximum of 6 sessions
Drug: platelet-rich plasma
platelet-rich plasma, metformin and cryotherapy in treatment of non-genital warts
Experimental: Cryotherapy
Group 3: will include 36 patients with multiple common, plantar and/or plane warts. They will receive cryotherapy sessions every two weeks until complete clearance or for a maximum of 6 sessions.
Other: cryotherapy
platelet-rich plasma, metformin and cryotherapy in treatment of non-genital warts

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete resolution of the wart(s) by disappearance of the wart and return of the normal skin markings
Time Frame: 3 months
Complete resolution of the wart(s) by disappearance of the wart and return of the normal skin markings
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
•Change in size in millemeter
Time Frame: 3 months
Change in size in millemeter
3 months
•Decrease in numbers of the warts
Time Frame: 3 months
Decrease in numbers of the warts
3 months
•Recurrence rates at 3 months for wart(s) with complete resolution.
Time Frame: 3 months
Recurrence rates at 3 months for wart(s) with complete resolution.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Investigators

  • Principal Investigator: Eman Mohamed Kamal Elsayed Youssef, prof, Professor of Dermatology and Venereology Faculty of Medicine, Assiut University
  • Principal Investigator: Alaa Mohamed Mahmoud Hamdy Ghazally, Lecturer, Lecturer of Dermatology and Venereology Faculty of Medicine, Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 14, 2024

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

April 1, 2025

Study Registration Dates

First Submitted

February 9, 2024

First Submitted That Met QC Criteria

November 14, 2024

First Posted (Actual)

November 15, 2024

Study Record Updates

Last Update Posted (Actual)

November 15, 2024

Last Update Submitted That Met QC Criteria

November 14, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRP, Metformin in warts

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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