Chlorhexidine and Garlic Extract as Potential Topical Virucidal Therapeutic Agents of Non-Genital Warts

Study Overview
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Brief Summary
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Aim(s) of the Research: Evaluate the efficacy and safety of topical chlorhexidine (2%) solution vs garlic extract (15%) solution in treating non-genital warts. Explore possible relation between therapeutic response with demographic/clinical data. Identify patients satisfaction with each agent.

Detailed Description
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Cutaneous warts or verruca are common, benign skin growths caused by human papilloma virus (HPV). There are several therapeutic modalities for warts: include destructive agents (keratolytics, cryotherapy, curettage and cautery, laser, photodynamic therapy), antimitotic agents (podophyllin, bleomycin, retinoids), immune stimulants (topical sensitizers, cimetidine), and topical virucidal agents (formaldehyde, glutaraldehyde) Unfortunately, no single treatment is satisfactory for all patients. Chlorhexidine gluconate(CHX) is a gluconate salt with a broad-spectrum antiseptic action against Gram-Positive, Gram-negative bacteria, aerobes, facultative anaerobes, and fungi such action is mediated through increasing the permeability of the cell walls of microbes, causing their lysis. Additionally, evidence indicates an in vitro effect against many viruses such as influenza A, parainfluenza, herpes virus 1, cytomegalovirus, hepatitis B, HIV and SARS-CoV-2. It was hypothesized that the biophysiological mechanisms for the virucidal effect of CHX may be exerted through lysis of viral envelope, deterioration of nucleotide carbon chains, and inactivation and/or blocking of viral proteins. Garlic (Allium sativum) is one of the most widely used medicinal plants with high therapeutic effects. Clinical effectiveness of oral and topical garlic extract may be attributed to its antimicrobial, antioxidant, anti-inflammatory, anticancer and aging prevention effects. However, the mechanisms of these actions are not clearly known. In vitro studies on garlic showed that garlic may enhance natural killer (NK) cells, which are an important part of the immune system in fighting cancers, viruses and certain bacteria. Previous studies showed garlic extract was effective on complete resolution of cutaneous wart. Chlorhexidine has not been used for treatment of warts in previous studies so we decided to explore its efficacy in treatment of warts.

Official Title
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Chlorhexidine and Garlic Extract as Potential Topical Virucidal Therapeutic Agents of Non-Genital Warts: A Prospective, Randomized, Controlled, Blinded Clinical Trial

Conditions
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Non-Genital Warts

Intervention / Treatment
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* Drug: garlic extract (15%) solution
* Drug: topical chlorhexidine (2%) solution
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with the clinical diagnosis of common or plantar warts. Exclusion Criteria: Pregnancy and lactation. Chronic systemic diseases such as chronic renal failure, hepatic insufficiency, and cardiovascular disorders. Patients with inflamed lesions Use of systemic or topical treatments during the last month before enrollment. Individuals with history of allergic reactions to garlic or chlorhexidine Patient with generalized dermatitis or allergic skin disorders
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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: garlic extract<br>Garlic will be collected from Medicinal Plant station, Pharmacognosy Department, Faculty of Pharmacy, Assiut University. The fresh garlic bulbs will be crushed. Extraction will be done using maceration method with Ethanol for 24 h at room temperature. Freeze-drying method will be used to remove solvent and give dry powder. Dry powder will be mixed with isopropyl alcohol in a ultrasonic bath to solve thoroughly. The soluble garlic extract will be added to a mixture of Polyethylene Glycol. The topical garlic formulation will be prepared for each time for two weeks-use and will be kept in dark glass containers in refrigerator till prescription. •Group 1: will apply Vaseline over the normal skin surrounding the lesion(s) then a cotton soaked with garlic extract (15%) solution will be applied under occlusion with a plastic tape for one hour and then washed by tap water daily for 6 weeks. | Drug: garlic extract (15%) solution<br>* •Group 1: will apply Vaseline over the normal skin surrounding the lesion(s) then a cotton soaked with garlic extract (15%) solution will be applied under occlusion with a plastic tape for one hour and then washed by tap water daily for 6 weeks.<br>|
| Experimental: chlorhexidine<br>Chlorhexidine 4% (Laries, manufactured by: Smartec Egypt) will be diluted with equal amount of distilled water to obtain a concentration of 2%. •Group 2: will apply Vaseline over the normal skin surrounding the lesion(s) then a cotton soaked with topical chlorhexidine (2%) solution will be applied under occlusion with a plastic tape for one hour and then washed by tap water daily for 6 weeks. | Drug: topical chlorhexidine (2%) solution<br>* •Group 2: will apply Vaseline over the normal skin surrounding the lesion(s) then a cotton soaked with topical chlorhexidine (2%) solution will be applied under occlusion with a plastic tape for one hour and then washed by tap water daily for 6 weeks.<br>|
| Placebo Comparator: group3<br>•Group 3: (control) will use normal saline 0.9% as a placebo (they will be treated later on after completion of the study using any of the standard therapies for non-genital warts). | Drug: Saline<br>* •Group 3: (control) will use normal saline 0.9% as a placebo (they will be treated later on after completion of the study using any of the standard therapies for non-genital warts).<br>* Other names: saline 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ●Evaluate the efficacy and safety of topical chlorhexidine (2%) solution vs garlic extract (15%) solution in treating non-genital warts | will be evaluated by changing in the size (using ruler) and the number of lesions. | 6weeks up to 3 month | 
| ●Side effects (systemic of local) as burning, itching, erythema, pigmentary changes, ulceration, and scarring | will be evaluated at each visit. | 6weeks up to 3 month |