The Evaluation of Vitiligous Lesions Repigmentation After the Administration of Atorvastatin Calcium Salt and Simvastatin-acid Sodium Salt in Patients With Active Vitiligo

Study Overview
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Brief Summary
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The aim of this study is to evaluate the influence of simvastatin and atorvastatin on vitiligous lesions in patients with non-segmental vitiligo.

Detailed Description
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According to available data, statins act through several immunological pathways, potentially reversing undesirable phenomena underlying autoimmune vitiligo pathogenesis. A study has been designed as a single-center, randomized, double-blind, placebo-controlled pilot study with the enrollment of at least 20 active non-segmental vitiligo patients presenting with vitiligous lesions on both upper and lower limbs. Clinical effects of ointments containing 1% simvastatin-acid sodium salt or 1% atorvastatin calcium salt applied on a preselected limb will be assessed in comparison with vehicle ointment applied on the opposite limb. All study participants will undergo clinical evaluation using Body Surface Area (BSA) and Vitiligo Area Scoring Index (VASI) scales at baseline, week 4, week 8 and week 12 time points. Precise assessment of skin lesions will be performed using photographic documentation obtained during each study visit and processed with NIS-Elements software.

Official Title
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The Evaluation of Vitiligous Lesions Repigmentation After the Administration of Atorvastatin Calcium Salt and Simvastatin-acid Sodium Salt in Patients With Active Vitiligo (EVRAAS)

Conditions
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Non-segmental Vitiligo

Intervention / Treatment
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* Drug: 1% simvastatin-acid sodium salt ointment
* Drug: 1% atorvastatin calcium salt ointment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients of Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz provision of an informed consent form prior to any study procedures diagnosis of non-segmental acrofacial vitiligo with upper and lower limbs involvement active vitiligo, defined as appearance of new areas of depigmentation or progression of existing areas of depigmentation within 3 months preceding screening male or non-pregnant female patients aged 18 to 80 years confirmed valid health insurance all inclusion criteria must be met Exclusion Criteria: pregnancy or breast-feeding diagnosis of segmental, mixed, unclassified or undefined vitiligo hypersensitivity to simvastatin or atorvastatin any statins use within 8 weeks preceding eligibility screening systemic immunosuppressive/immunomodulating i.e. cyclosporine A, corticosteroids within 4 weeks preceding eligibility screening or azathioprine, methotrexate, mycophenolate mofetil, Janus kinase - JAK within 8 weeks preceding eligibility screening phototherapy due to vitiligo or any other medical conditions within the 4-week period preceding eligibility screening any topical or systemic additional vitiligo treatment (e.g. antioxidants, ginkgo biloba, dermo-cosmetics) within 4 weeks preceding screening surgical treatment of vitiligous lesions within past 4 weeks hypersensitivity to statins decompensated autoimmune or internal diseases alcohol or drug abuse skin malignancies (currently or history of skin malignancy within 5 years preceding screening) presence of skin characteristics that may interfere with study assessments patients currently participating in any other clinical study uncooperative patients none of the above can be met

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1% simvastatin-acid sodium salt ointment<br>1% simvastatin-acid sodium salt ointment applied onto a predefined limb compared with placebo ointment applied onto an opposite limb | Drug: 1% simvastatin-acid sodium salt ointment<br>* 1% simvastatin-acid sodium salt ointment applied onto a predefined limb<br>* Other names: simvastatin;|
| Active Comparator: 1% atorvastatin calcium salt ointment<br>1% atorvastatin calcium salt ointment applied onto a predefined limb compared with placebo ointment applied onto an opposite limb | Drug: 1% atorvastatin calcium salt ointment<br>* 1% atorvastatin calcium salt ointment applied onto a predefined limb<br>* Other names: atorvastatin;|
| Placebo Comparator: Vehicle ointment<br>Placebo ointment applied onto limbs opposite to treated with active substances | Drug: 1% simvastatin-acid sodium salt ointment<br>* 1% simvastatin-acid sodium salt ointment applied onto a predefined limb<br>* Other names: simvastatin;Drug: 1% atorvastatin calcium salt ointment<br>* 1% atorvastatin calcium salt ointment applied onto a predefined limb<br>* Other names: atorvastatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of repigmentation of vitiligous lesions achieved after the administration of 1% simvastatin-acid sodium salt or 1% atorvastatin calcium salt ointments compared to vehicle ointments after a 12-week study period. | change from baseline in repigmentation on BSA and VASI scale at 12 weeks | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | number of adverse events and serious adverse events associated with treatment | 12 weeks | 
| percentage of patients who achieved particular response rate as follows none 0%; poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% in each arm assessed as a relative reduction in lesional skin area | number of: poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% responders in each arm assessed as a relative reduction in lesional skin area (in sqare centimeters) | 12 weeks | 
| percentage of patients who achieved particular response rate as follows none 0%; poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% in each arm assessed as a relative reduction in BSA scale | number of: poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% responders in each arm assessed as a relative reduction in BSA scale | 12 weeks | 
| percentage of patients who achieved particular response rate as follows none 0%; poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% in each arm assessed as a relative reduction in VASI scale | number of: poor 1-25%; moderate 26-50%; good 51-75%; excellent >75% responders in each arm assessed as a relative reduction in VASI scale | 12 weeks | 
| comparison of simvastatin and atorvastatin efficacy between study participants | comparison of BSA and VASI scale change between simvastatin and atorvastatin arms | 12 weeks | 
| the association between disease duration and repigmentation rate in study arms | the association between disease duration and repigmentation rate in study arms | 12 weeks | 
| the association between estimated daily ointment use (grams per square centimeter skin) and repigmentation rate | the association between estimated daily ointment use (grams per square centimeter skin) and repigmentation rate | 12 weeks |