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

Phase 3
Completed
Conditions
Non-segmental Vitiligo
Interventions
Registration Number
NCT04942860
Lead Sponsor
Nicolaus Copernicus University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
25
Inclusion Criteria
  1. Patients of Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz
  2. Provision of an informed consent form prior to any study procedures
  3. Diagnosis of non-segmental acrofacial vitiligo with upper and lower limbs involvement
  4. Active vitiligo, defined as appearance of new areas of depigmentation or progression of existing areas of depigmentation within 3 months preceding screening
  5. Male or non-pregnant and non-breastfeeding female patients aged 18 to 80 years
  6. Women must use effective contraception one month preceding treatment, during treatment and 6 months after completing treatment.
  7. Confirmed valid health insurance
Exclusion Criteria
  1. Diagnosis of segmental, mixed, unclassified or undefined vitiligo
  2. Pregnancy and breastfeeding
  3. Hypersensitivity to methotrexate or any of the excipients
  4. 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
  5. Phototherapy due to vitiligo or any other medical conditions within the 4-week period preceding eligibility screening
  6. Any topical or systemic additional vitiligo treatment (e.g. antioxidants, ginkgo biloba, dermo-cosmetics) within 4 weeks preceding screening
  7. Surgical treatment of vitiligous lesions within past 4 weeks
  8. Severe liver dysfunction [bilirubin> 5 mg / dL (85.5 μmol / L)], including cirrhosis and hepatitis
  9. Severe renal impairment (eGFR <20 ml / min),
  10. Disorders of the hematopoietic system, bone marrow disorders (leukopenia, thrombocytopenia, anemia),
  11. Immunodeficiencies, including HIV infection
  12. Severe acute or chronic infections such as tuberculosis
  13. Alcohol abuse
  14. Mouth ulcers and known active gastric or duodenal ulcer disease
  15. Recent surgical wounds.
  16. Skin malignancies (currently or history of skin malignancy within 5 years preceding screening)
  17. Presence of skin characteristics that may interfere with study assessments
  18. Patients currently participating in any other clinical study
  19. Uncooperative patients

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Methotrexate 1% gel1% Methotrexate gel1% methotrexate gel applied onto a predefined limb
Methotrexate 0.5% gel0.5% Methotrexate gel0.5% methotrexate gel applied onto a predefined limb
Vehicle gel0.5% Methotrexate gelVehicle gel applied onto a predefined limb
Vehicle gel1% Methotrexate gelVehicle gel applied onto a predefined limb
Primary Outcome Measures
NameTimeMethod
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 period12 weeks

change from baseline in repigmentation on VASI scale at 12 weeks

Secondary Outcome Measures
NameTimeMethod
the association between disease duration and repigmentation rate in study arms12 weeks

the association between disease duration and repigmentation rate in study arms

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 scale12 weeks

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

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 scale12 weeks

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

comparison of 1% methotrexate and 0.5% methotrexate gel efficacy between study participants12 weeks

comparison of VASI scale change between study arms

rate of adverse events during treatment as assessed by CTCAE v4.012 weeks

number of adverse events related to study treatment

Trial Locations

Locations (1)

Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Faculty of Medicine in Bydgoszcz

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Bydgoszcz, Cuiavian-Pomeranian, Poland

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