The Evaluation of Vitiligous Lesions Repigmentation After Topical Administration of Methotrexate in Patients With Active Vitiligo

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to evaluate the influence of two concentrations of methotrexate on vitiligous lesions in patients with non-segmental vitiligo

Detailed Description
-----------------
Methotrexate, synthesized in the 1950s as an anticancer drug with an antiproliferative effect, is currently one of the most commonly used immunosuppressive agents in dermatology. The use of small, non-oncological doses has revealed its anti-inflammatory properties, including the impact on a number of cytokines involved in the pathogenesis of autoimmune diseases. It has been shown that treatment with methotrexate reduces the levels of TNF-alpha-producing T cells, while the number of IL-10 producing T cells increases. Methotrexate also inhibits the synthesis of interferon-γ. The above considerations justify the use of topical methotrexate in patients with vitiligo in order to obtain repigmentation. A study has been designed as a single-center, randomized, double-blind, placebo-controlled pilot study with the enrollment of up to 100 active non-segmental vitiligo patients presenting with vitiligous lesions on both upper and lower limbs. Clinical effects of gel containing 1% methotrexate or 0.5% methotrexate 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
-----------------
The Evaluation of Vitiligous Lesions Repigmentation After Topical Administration of Methotrexate in Patients With Active Vitiligo

Conditions
-----------------
Non-segmental Vitiligo

Intervention / Treatment
-----------------
* Drug: 1% Methotrexate gel
* Drug: 0.5% Methotrexate gel


Participation Criteria
=================
Eligibility Criteria
-----------------
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 and non-breastfeeding female patients aged 18 to 80 years Women must use effective contraception one month preceding treatment, during treatment and 6 months after completing treatment. Confirmed valid health insurance Exclusion Criteria: Diagnosis of segmental, mixed, unclassified or undefined vitiligo Pregnancy and breastfeeding Hypersensitivity to methotrexate or any of the excipients 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 Severe liver dysfunction [bilirubin> 5 mg / dL (85.5 μmol / L)], including cirrhosis and hepatitis Severe renal impairment (eGFR <20 ml / min), Disorders of the hematopoietic system, bone marrow disorders (leukopenia, thrombocytopenia, anemia), Immunodeficiencies, including HIV infection Severe acute or chronic infections such as tuberculosis Alcohol abuse Mouth ulcers and known active gastric or duodenal ulcer disease Recent surgical wounds. 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

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methotrexate 1% gel<br>1% methotrexate gel applied onto a predefined limb | Drug: 1% Methotrexate gel<br>* 1% methotrexate gel applied onto a predefined limb<br>* Other names: methotrexate;|
| Active Comparator: Methotrexate 0.5% gel<br>0.5% methotrexate gel applied onto a predefined limb | Drug: 0.5% Methotrexate gel<br>* 0.5% methotrexate gel applied onto a predefined limb<br>* Other names: methotrexate;|
| Placebo Comparator: Vehicle gel<br>Vehicle gel applied onto a predefined limb | Drug: 1% Methotrexate gel<br>* 1% methotrexate gel applied onto a predefined limb<br>* Other names: methotrexate;Drug: 0.5% Methotrexate gel<br>* 0.5% methotrexate gel applied onto a predefined limb<br>* Other names: methotrexate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of repigmentation of vitiligous lesions achieved after the administration of 1% methotrexate or 0.5% methotrexate gels compared to vehicle gel after a 12-week study period | change from baseline in repigmentation on BSA scale at 12 weeks | 12 weeks | 
| evaluation of repigmentation of vitiligous lesions achieved after the administration of 1% methotrexate or 0.5% methotrexate gels compared to vehicle gel after a 12-week study period | change from baseline in repigmentation on VASI scale at 12 weeks | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 1% methotrexate and 0.5% methotrexate gel efficacy between study participants | comparison of BSA scale change between study arms | 12 weeks | 
| comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants | comparison of VASI scale change between study 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 | 
| rate of adverse events during treatment as assessed by CTCAE v4.0 | number of adverse events related to study treatment | 12 weeks |