Infections

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Warts

Communicable Diseases

Papillomavirus Infections

Virus Diseases

DNA Virus Infections

Skin Diseases

Skin Diseases, Viral

Tumor Virus Infections

Skin Diseases, Infectious

All Drugs and Chemicals

Immunomodulating Agents

Intralesional injection of 0.3ml candida antigen into largest wart at baseline visit and then every 3 weeks +/- 3 days for a maximum of 10 treatments.

Candida Antigen

Mayumi Nakagawa, MD, PhD

The purpose of this study is to look at how people respond to the treatment of warts through use of the Candida antigen to get an immune response to rid the body of human papillomavirus (HPV). The immune system is the part of the body that fights infections like HPV which causes warts. This research study will examine the response of your wart when injected with a portion of a common yeast (candida) which is the study drug. Your immune system response will also be looked at by doing a test called an ELISPOT assay. This test is done on blood samples. The results of this test may help us to determine how the Candida antigen affects your wart.

The use of recall antigens for treating warts is not yet Food and Drug Administration (FDA) approved. The primary goal of this work was to assess the safety of Candin as an investigational new drug (IND) for the treatment of warts. In addition, clinical resolution of treated and untreated warts was evaluated and immunologic responses were examined using an ex vivo interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay in order to elucidate the immunologic mechanisms behind the successful regression of warts in patients undergoing Candin injection immunotherapy.

Study With Candida Antigen for Treatment of Warts

A Phase 1 Study to Evaluate the Immunologic Mechanisms Underlying Wart Resolution After Intralesional Immunotherapy With Candida Antigen

Immunologic responses from peripheral blood mononuclear cells collected prior to vaccination and post-vaccination were measured by ex vivo interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) assay to human papillomavirus type 57 L1-peptide.

When the participant completed the protocol, clinical resolution of the injected wart was determined by the overall percentage of resolution from the initial visit. Participants were classified as 'complete responders' if they had complete resolution of the injected wart, 'partial responders' if the injected wart regressed between 25% and 99%, and 'non-responders' if they had not achieved at least 25% regression of the injected wart.

When the participant completed the protocol, clinical resolution of 1st anatomically distant, non-injected wart was determined by the overall percentage of resolution from the initial visit.

When the participant completed the protocol, clinical resolution of 2nd anatomically distant, non-injected wart was determined by the overall percentage of resolution from the initial visit.

Allermed Laboratories, Inc.

University of Arkansas

Mayumi Nakagawa

All patients enrolled into the study were treated with intralesional injection of 0.3ml candida antigen into largest wart at baseline visit and then every 3 weeks +/- 3 days for a maximum of 10 treatments.

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Complete responder

Partial responder

Non-responder

The participants were analyzed if they completed the protocol by achieving complete resolution of the treated wart, receiving the maximum of 10 treatments, or by having less than 25% resolution of the treated wart after 5 treatments.

Number of Participants With Clinical Resolution of Injected Wart

Complete resolution of 1st non-injected wart

Partial resolution of 1st non-injected wart

Participants with 1st anatomically distant, non-injected wart were analyzed.

Number of Participants With Clinical Resolution of 1st Anatomically Distant, Non-injected Wart

The participants with 2nd anatomically distant, non-injected wart were analyzed.

Number of Participants With Clinical Resolution of 2nd Anatomically Distant, Non-injected Wart

The interferon-γ enzyme-linked immunospot assay was performed on available samples from participants who completed the study.

Number of Participants With Immune Response to Human Papillomavirus Type 57 (HPV-57) L1-peptide

Overall Study

Necrosis

Pharmaceutical Solutions

Complement System Proteins

Complement C3

Patient receive 0.1 mL of diluted preparation of candida solution at 2 weeks interval for the maximum of 5 sessions

Patient receive candida antigen immunotherapy and blood samples will be withdrawn before and after intervention

Candida antigen

The investigators explore the role of the complement pathway and T helper 1 immune response in clinical response to Candida immunotherapy via complement component and tumor necrosis factor, respectively.

39 patients are enrolled in the study They suffer from chronic recurrent cutaneous warts Patients receive Candida antigen immunotherapy vial intra-lesional injection every 2 weeks till complete resolution or the maximum of 5 sessions Blood samples are withdrawn before and after intervention C3, C4, MBL, C3C and TNF alpha serum levels are measured

Complement Component 3c and Tumor Necrosis Factor-α in Patients With Human Papillomavirus-Induced Cutaneous Warts

Zagazig University

Principal investigator

Mouth and Tooth Diseases

Rare Diseases

Measles

Rubella

Mumps

Vaccines

Immunologic Factors

Randomized double-blinded comparative effectiveness and safety clinical trial

Intralesional antigen immunotherapy

Warts can be resistant to treatment or return despite the use of many therapeutic modalities. Combining immunotherapy might contribute to better response rates, particularly in recalcitrant warts, which is a real therapeutic challenge. The purpose of this study was to assess the effectiveness and safety of a triple intralesional immunotherapy combination composed of PPD, Candida antigen and MMR versus either agent alone in the management of multiple recalcitrant warts.

This study included 160 patients with multiple (\>3 warts) recalcitrant (at least 6 months duration and who did not respond to at least 2 treatment modalities) warts of different sites, size and duration, with or without distant warts after approval of the Institutional Review Board of Faculty of medicine, Zagazig university. They were randomly assigned to one of four groups (each with 40 patients): PPD, Candida antigen, MMR, or combination of the 3 antigens. Injections into the biggest wart were repeated every two weeks until clearance or for a total of five sessions.

Triple Antigen vs Monoantigen Immunotherapy for Warts

Triple Intralesional Antigen Immunotherapy Versus Monoantigen in the Treatment of Multiple Recalcitrant Warts

Hypoglycemic Agents

Dermatologic Agents

Micronutrients

Insulin

Insulin, Globin Zinc

Zinc Sulfate

Zinc

Astringents

The first group will receive Intralesional injection of Candidal antigen with a dose of (0.1ml -0.3ml) by insulin syringe in the largest wart at the first visit.( Only those patients who showed a positive response to the Candida test antigen).I njections will be repeated for all patients into the same lesion every 3 weeks for three treatment sessions. Follow up for next six months for any recurrences.

Storage: A 1ml multidose vial of candidal antigen (Candin) which is an intradermal test antigen, stored between 2c-8c.

The second group will receive an IL injection of 2%Zn sulfate with a dose of (0.1ml-0.3ml) by insulin syringe ,in the largest one .the wart is injected with the solution till blanching or bleb formation. Subcutaneous injections and acral parts such as fingers and toes will be avoided, as it may cause vascular necrosis \[19\]. Injections will be repeated for all patients into the same lesion every 2 weeks for three treatment sessions.Follow up for next six months for any recurrences.

Preparation of 2% zinc sulfate: A measure of 2g. of zinc sulfate powder is to be dissolved in 100 ml of sterile distilled water and autoclaved at 95c for 20 min(20).

Eman Mohamed Kamal, MD

Radwa Bakr, MD

Eman Kamal, MD

Warts are common and infectious viral diseases of the skin and are prevalent worldwide. Warts are caused by the human papilloma virus (HPV), which has more than 100 strains; some of them are known to be premalignant .Although warts can appear at any age, they are more common in children and adolescents. The prognosis of warts cannot be predicted. In some patients they may spontaneously disappear, whereas others show persistence and progression with spreading to other body sites, leading to physical and emotional distress to the patients. \[ 1 \].

Forty percent of children spontaneously clear in two years without treatment owing to natural immunity \[ 2,3.\]. However, warts can persist and increase in size and number \[2\] .

Warts may reflect a localized or systemic cell-mediated immune (CMI) deficiency to HPV. Various reasons like lack of production of memory T cells to target HPV infection, failure of clonal expansion of lymphocytes to adequate stimulation, inability of T lymphocytes to traffic to sites of infection and weak effector response mechanism have been hypothesized. \[4\] .\] Consequently, warts are particularly exuberant in patients with Hodgkin's disease, AIDS and those on immunosuppressant \[ 5 \].

The conventional modalities in treatment of warts include destructive therapies such as salicylic acid, trichloroacetic acid, cryotherapy, silver nitrate, phenol, canthiridin, electrocautary, surgical interventions and lasers; antiproliferative agents such as bleomycin, vitamin D analogs, podophyllin, and 5-fluro uracil; antiviral agents such as cidofovir and retinoids. Because of the cumbersome nature of these procedures and a high risk of recurrence, immunotherapy is becoming more and more popular, especially in the treatment of refractory cutaneous and genital warts \[ 6 \] . It enhances recognition of the virus by the immune system. This allows not only clearing of the treated wart, and frequently warts at distant anatomic sites, but also may prevent future clinical infection \[ 7 \] .

Immunotherapy in warts can be administered by various methods. The first method is topical application of certain inorganic molecules that are capable of eliciting a contact hypersensitivity reaction with secondary activation of an immunological response \[ 8 \] . A second modality is the use of oral immune modulators such as cimetidine and zinc(10mg/kg/day for 2months) \[ 9 , 10 \] .

A third method is Intralesional injection of immunotherapeutic agent that utilizes the ability of the immune system to mount a delayed type hypersensitivity response to various antigens and also the wart tissue leading to production of Th1 cytokines which activate cytotoxic and natural killer cells to eradicate HPV infection. This clears not only the local warts but also distant warts unlike traditional wart therapies \[ 11 \] .

There are a few side effects reported by most of the studies. The most common side effect was pain and discomfort during injection, however, serious side effects such as vitiligo-like depigmentation and painful purple digit have also been reported \[ 12 \] .

Zinc is important for immune regulation as it stimulates the leucocytes and natural killer cells. It has been shown that there is a deficiency of zinc in patients with multiple or recurrent warts \[ 13 ,14 \].The use of zinc in treatment of warts was proven in many studies either in the topical form or systemic oral therapy \[ 15 \].. However, Little studies have utilized intralesional injection of 2% zinc sulfate solution for the treatment of common wart one of them was of \[16\] .

Intralesional Candidal Antigen Versus Intralesional Zinc Sulphate in Treatment of Cutaneous Warts

Intralesional Candidal Antigen Versus Intralesional Zinc Sulphate in Treatment of Cutaneous Warts, A Randomized Clinical Trial

Assiut University

principle investigator

Condylomata Acuminata

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Genital Diseases

Urogenital Diseases

Antineoplastic Agents

Petrolatum

Podophyllin

Keratolytic Agents

Intralesional Mumps, measles and rubella (MMR) vaccine in genital warts

intralesional candida antigen in genital warts

Intralesional injection of 0.5 ml MMR vaccine in the largest lesion . Injections will be repeated into the same lesion every 2 weeks for a maximum of three treatment sessions.

MMR vaccine

Intralesional injection of Candidal antigen with a dose of (0.1ml -0.3ml) by an insulin syringe in the largest wart at the first visit. Injections will be repeated for all patients into the same lesion every 2 weeks for a maximum of three treatment sessions.

It will be applied to the wart by using a cotton tipped swab once a week . The procedure will be limited to 10 cm2 per session .Surrounding skin will be protected by Vaseline. Podophyllin will be washed 4 hour after application . The procedure will be repeated every week till 6 weeks .

Topical Podophyllin

Hisham Zayan, MD

Yasmin tawfik, MD

This study compares the safety and efficacy of intralesional Candidal antigen versus Intralesional MMR vaccine versus podophyllin for treatment of genital warts.

Anogenital human papillomavirus (HPV) is a highly prevalent sexually transmitted infection ,seen predominantly in young adults.

Condyloma acuminata or benign anogenital warts are typically caused by HPV-6 OR 11 which are considered low risk types.Persistent infection with high risk HPV types predominantly HPV-16 and 18 is the primary and major cause of cervical cancers and a subset of vaginal,vulvar, penile , anal ,oropharyngeal and rarely squamous cell carcinoma of the digits.

Warts may reflect a localized or systemic cell-mediated immune (CMI) deficiency to HPV.

Anogenital warts may appear as a single lesion or in clusters as flat, flesh-coloured to pigmented plaques or rough-surfaced papules and exophytic nodules.

The conventional modalities in treatment of warts include destructive therapies such as salicylic acid, trichloroacetic acid, cryotherapy, silver nitrate, phenol, cantharidin, surgical interventions and lasers; antiproliferative agents such as bleomycin, podophyllin, podophyllotoxin, and 5-fluro uracil; antiviral agents such as cidofovir and retinoids.

Because of the cumbersome nature of these procedures and a high risk of recurrence, immunotherapy is becoming more and more popular, especially in the treatment of refractory cutaneous and genital warts.It enhances recognition of the virus by the immune system. immunotherapy not only causes a resolution of the treated wart but also leads to clearance of distant warts, at least in a subset of the responders.

Immunotherapy in warts can be administered by various methods. The first method is topical application of certain inorganic molecules that are capable of eliciting a contact hypersensitivity reaction with secondary activation of an immunological response .or even topical applications of immune modulators like imiquimod,A second modality is the use of oral immune modulators such as cimetidine,and levamisole .

A third method is Intralesional injection of immunotherapeutic agent that utilizes the ability of the immune system to mount a delayed type hypersensitivity response to various antigens and also the wart tissue leading to production of Th1 cytokines which activate cytotoxic and natural killer cells to eradicate HPV infection.

Immunotherapy with different skin test antigens like Candida, mumps or trichophyton antigen is a relatively new treatment option for warts. Candida antigen reported success in majority of patients treated with this test antigen .

Mumps, measles and rubella (MMR) vaccine is a freeze-dried preparation of live attenuated strains of measles, mumps and rubella viruses (0.5 ml/dose). In some of the previous studies, it has been shown that mumps-measles-rubella (MMR) vaccine results in regression of warts via immunomodulation and induction of immune system.

Efficacy of Intralesional MMR Vaccine,Intralesional Candidal Antigen&Topical Podophyllin in Treatment of Genital Warts

The Efficacy of Intralesional Measles, Mumps, Rubella (MMR) Vaccine, Intralesional Candidal Antigen and Topical Podophyllin in Treatment of Genital Warts: A Comparative Study

Assess cure rate of MMR vaccine and candida antigen and topical podophyllin in treatment of genital warts (complete disappearance of lesions) in 45 days duration and compare efficacy of the measures.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study With Candida Antigen for Treatment of Warts	NCT00569231	Warts HPV	Candida Antigen	18 Years - 50 Years	University of Arkansas
Complement Component 3c and Tumor Necrosis Factor-α in Patients With Human Papillomavirus-Induced Cutaneous Warts	NCT04399577	Warts	Candida antigen	9 Years - 45 Years	Zagazig University
Triple Antigen vs Monoantigen Immunotherapy for Warts	NCT05254561	Triple Intrales...	Intralesional a...	10 Years - 70 Years	Zagazig University
Intralesional Candidal Antigen Versus Intralesional Zinc Sulphate in Treatment of Cutaneous Warts	NCT03158168	Warts	Candida Antigen Zinc Sulfate	5 Years - 50 Years	Assiut University
Efficacy of Intralesional MMR Vaccine,Intralesional Candidal Antigen&Topical Podophyllin in Treatment of Genital Warts	NCT03853785	Condylomata Acu...	MMR vaccine Candida antigen Topical Podophy...	3 Years - 50 Years	Assiut University

Spots Global Cancer Trial Database for candida antigen