Efficacy and Safety of Hepatitis B Virus Vaccine(HBV) in Treatment of Cutaneous Warts

Study Overview
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Brief Summary
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Aim of the work: Evaluate efficacy and safety of Intralesional HBV vaccine injection as a treatment of plane and genital warts. Evaluate efficacy and safety of Intramuscular HBV vaccine injection as a treatment of plane and genital warts. Compare the efficacy of different doses(0.3ml vs 0.5ml )of intralesional HBV vaccine injection for treatment of plane and genital warts. Compare the efficacy of intralesional HBV vaccine injection vs Intramuscular HBV vaccine injection in treatment of plane and genital warts.

Detailed Description
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INTRODUCTION: Warts are common, benign and epithelial proliferations and growths affecting the skin and/or the mucosa caused by human papilloma virus (HPV) which is a double stranded DNA virus with a worldwide distribution. There are approximately 218 types of HPV identified as causing infections in humans . Infection occurs predominantly via direct contact, although skin lesions can be transmitted indirectly, via contaminated surfaces, Abrations and microtraumas expose the basal layer keratinocytes and facilitate contagion . The clinical manifestations of HPV-related diseases vary depending upon the HPV type and the site of inoculation .Extragenital cutaneous warts can present as common warts, plane warts, plantar warts .HPV infection is one of the most common sexually transmitted infections with the most common manifestation of HPV in the genital area is anogenital warts or condylomata acuminate . Infections due to these viruses may result in a wide spectrum of clinical manifestations in the skin and mucosa. Although cutaneous warts are mostly benign with spontaneous resolution after months or years in healthy patients. Nonetheless, they can grow, cause discomfort or embarrassment to patients, or persist for months or years, increasing viral transmission between individuals. Also, anogenital warts caused by high risk strains possess an oncogenic potential . 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 treatment modalities include physical destruction (e.g., cryotherapy, electrosurgery, ablative laser, or surgical removal), chemical destruction (e.g., salicylic acid or trichloroacetic acid), and anti-proliferative agents (e.g., podophyllin, 5-fluorouracil or bleomycin). Unfortunately, no treatment has yet shown 100% effectiveness as a cure. Furthermore these modalities have side-effects (e.g. pain, erythema, burning sensation and scarring) .Classical treatment lines are associated with high recurrence rates as they are limited to local application and do not act systemically .So, there is a need for therapies with a greater efficacy and minimal side-effects . Immunotherapeutic agents act by enhancing the host cell-mediated immunity that helps to eliminate the virus rather than simply destroying visible skin lesions and have recently received increasing attention for the treatment of warts because of their non-destructive action, high safety profiles, promising results, and low recurrence rates. Contact immunotherapy using contact sensitizers (diphenylcyclopropenone or dinitrochlorobenzene), topical imiquimod, oral cimetidine or intralesional immunotherapy has been attempted as viable immunotherapeutic options for treatment of warts. Intralesional immunotherapy has been assessed as an alternative therapeutic approach, particularly for cases of recalcitrant or multiple warts, since it may facilitate the clearance of not only the injected wart but also surrounding non-injected warts. Various immunotherapeutic agents including skin test antigens (mumps, Candida, and Trichophyton); the combined measles, mumps, and rubella vaccine(MMR); the tuberculin purified protein derivative(PPD); Mycobacterium w vaccine; and bacillus Calmette-Guérin(BCG) vaccine have been assessed. Hepatitis B virus (HBV) vaccine is a highly safe and effective DNA vaccine against HBV infection that is recommended for all infants at birth and for children. It is also recommended for adults at high risk for infection because of their jobs, lifestyle, or living situations. It is relatively cheap, easy to produce, and extremely stable. Besides, HBV vaccination is associated with the stimulation, not only of humoral immunity that induces antibody production against Hepatitis B surface antigen (HBsAg), but also of cell-mediated immunity, particularly T helper1 Th1 cytokines such as interferon γ( IFN-γ )and interleukin2(IL-2). Furthermore, HBV vaccine has the advantage of being a non-live vaccine that can be used safely in immunocompromised patients in contrast to the live vaccines such as measles, mumps, and rubella (MMR), Bacillus Calmette-Guerin (BCG) that may pose high risks to the immunocompromised patients . Only two researches studied the efficacy of intralesional HBV vaccine injection in treatment of multiple common warts. Both studies revealed low success rate (20.7% and 23.3% respectively) of intralesional HBV vaccine at a dose of 0.2ml injected into the largest wart in biweekly sessions for a maximum of 5 sessions. It Worth mentioning that one the two studies also examined the efficacy of intramuscular injection of HBV vaccine at higher doses (0.5 ml and 1 ml/ injection) for 3 injections and reported a complete clearance of common warts in 50% of the patients, which was statistically significant higher than percentage of those patients who achieved complete clearance after treatment with intralesional injection of HBV vaccine using 0.2 ml/session for five sessions. Whether this significant difference is related to the different treatment dosage or to the different administration routes is still to be unraveled by further studies.

Official Title
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Efficacy and Safety of Hepatitis B Virus Vaccine(HBV) in Treatment of Cutaneous Warts

Conditions
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Cutaneous Warts

Intervention / Treatment
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* Drug: Hepatitis B Virus Vaccine(HBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patients with multiple genital or plane warts of any site. Patients age above 10 years old No concurrent systemic or topical treatment of warts Exclusion Criteria: Pregnancy and lactation. 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. Patients with history of neuropathy or peripheral ischemia. Patients with signs of inflammation or infection. Patients with history of a serious systemic or anaphylactic reaction or allergy to a prior dose of HBV vaccine or to any of its components.

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group intralesional injection(0.3 ml)<br>Group 1: will include 22 patients with multiple plane or genital warts. They will be treated by intralesional injection of HBV vaccine at a dose of (0.3 ml) into the largest wart by an insulin syringe every 2-weeks until complete clearance or for a maximum of 5 sessions. | Drug: Hepatitis B Virus Vaccine(HBV)<br>* Hepatitis B Virus Vaccine(HBV)<br>|
| Other: Group intralesional injection(0.5 ml)<br>Group 2: will include 22 patients with multiple plane or genital warts. They will be treated by intralesional injection of HBV vaccine at a dose of (0.5 ml) into the largest wart by an insulin syringe every 2-weeks until complete clearance or for a maximum of 5 sessions. | Drug: Hepatitis B Virus Vaccine(HBV)<br>* Hepatitis B Virus Vaccine(HBV)<br>|
| Other: Group intramuscular injection<br>Group 3: will include 22 patients with multiple plane or genital warts. They will be treated by intramuscular injection of HBV vaccine at a dose of (0.5 ml)in patients who are 18 years or younger and (1ml)in patients older than 18 years in the deltoid muscle using a 25-gauge syringe every month until complete clearance or for a maximum of 3 months. | Drug: Hepatitis B Virus Vaccine(HBV)<br>* Hepatitis B Virus Vaccine(HBV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effectiveness of Hepatitis B virus vaccine(HBV) in treatment of cutaneous warts . | size of cutaneous warts in millimeters will be measured every visit | 10 weeks | 
| Effectiveness of Hepatitis B virus vaccine(HBV) in treatment of cutaneous warts . | number of cutaneous warts will be measured every visit | 10 weeks |