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

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

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

Study Overview

• Status: Completed
• Conditions: Non-segmental Vitiligo
• Intervention / Treatment: Drug: 1% simvastatin-acid sodium salt ointment; Drug: 1% atorvastatin calcium salt ointment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Poland
  • Cuiavian-Pomeranian
    • Bydgoszcz, Cuiavian-Pomeranian, Poland, 85094
      • Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University, Faculty of Medicine in Bydgoszcz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 female patients aged 18 to 80 years
6. confirmed valid health insurance

all inclusion criteria must be met

Exclusion Criteria:

1. pregnancy or breast-feeding
2. diagnosis of segmental, mixed, unclassified or undefined vitiligo
3. hypersensitivity to simvastatin or atorvastatin
4. any statins use within 8 weeks preceding eligibility screening
5. 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
6. phototherapy due to vitiligo or any other medical conditions within the 4-week period preceding eligibility screening
7. any topical or systemic additional vitiligo treatment (e.g. antioxidants, ginkgo biloba, dermo-cosmetics) within 4 weeks preceding screening
8. surgical treatment of vitiligous lesions within past 4 weeks
9. hypersensitivity to statins
10. decompensated autoimmune or internal diseases
11. alcohol or drug abuse
12. skin malignancies (currently or history of skin malignancy within 5 years preceding screening)
13. presence of skin characteristics that may interfere with study assessments
14. patients currently participating in any other clinical study
15. uncooperative patients

none of the above can be met

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1% simvastatin-acid sodium salt ointment; 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; 1% simvastatin-acid sodium salt ointment applied onto a predefined limb; Other Names: simvastatin
Active Comparator: 1% atorvastatin calcium salt ointment; 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; 1% atorvastatin calcium salt ointment applied onto a predefined limb; Other Names: atorvastatin
Placebo Comparator: Vehicle ointment; Placebo ointment applied onto limbs opposite to treated with active substances	Drug: 1% simvastatin-acid sodium salt ointment; 1% simvastatin-acid sodium salt ointment applied onto a predefined limb; Other Names: simvastatin; Drug: 1% atorvastatin calcium salt ointment; 1% atorvastatin calcium salt ointment applied onto a predefined limb; Other Names: atorvastatin

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% 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

Collaborators and Investigators

• Sponsor: Nicolaus Copernicus University
• Investigators: Principal Investigator: Rafal Czajkowski, Prof NCU, Head of Chair and Clinic of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Nicolaus Copernicus University in Torun, Ludwik Rydygier Medical College in Bydgoszcz

Publications and helpful links

General Publications

• Niezgoda A, Winnicki A, Kosmalski T, Kowaliszyn B, Krysinski J, Czajkowski R. The Evaluation of Vitiligous lesions Repigmentation after the Administration of Atorvastatin calcium salt and Simvastatin-acid sodium salt in patients with active vitiligo (EVRAAS), a pilot study: study protocol for a randomized controlled trial. Trials. 2019 Jan 25;20(1):78. doi: 10.1186/s13063-018-3168-4.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): April 30, 2019

Study Registration Dates

• First Submitted: August 5, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 11, 2017

Study Record Updates

• Last Update Posted (Actual): September 23, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Hypopigmentation; Vitiligo; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Calcium-Regulating Hormones and Agents; Atorvastatin; Calcium; Simvastatin
• Other Study ID Numbers: NCU 631

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No