Clinical Trial of Simvastatin to Treat Generalized Vitiligo

Study Overview
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Brief Summary
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The investigators purpose is to initiate a phase II, randomized, placebo-controlled clinical trial to test simvastatin, an FDA-approved medication for hypercholesterolemia, as a new treatment for vitiligo. The aims of this placebo-controlled study seek to determine the safety and potential efficacy of simvastatin 80mg daily versus placebo in adult male patients with generalized vitiligo. Additionally, the investigators will collect blood to examine the effect of simvastatin on autoreactive CD8+ T cells in vitiligo patients.

Detailed Description
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Vitiligo is an autoimmune disease caused by autoreactive CD8+ T lymphocytes that target melanocytes, and interferon-γ-induced CXCL10 plays an important role.1 Simvastatin inhibits interferon-γ signaling by blocking activation of STAT12 and prevented and reversed disease in our mouse model.3 A case report described a patient with vitiligo who repigmented with simvastatin.4 We conducted a small, randomized, double-blind, placebo-controlled, phase II clinical trial to test simvastatin as a treatment for vitiligo. After obtaining informed consent, we enrolled men ages 18 to 64 years with vitiligo affecting 3% to 50% of their body surface area (BSA). We excluded patients with a segmental presentation; those already taking 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor; those with existing thyroid disease; and women, based on their increased risk of simvastatin-induced myopathy.

Official Title
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A Phase-II, Randomized, Placebo-controlled Trial of Simvastatin in Generalized Vitiligo

Conditions
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Vitiligo

Intervention / Treatment
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* Drug: Simvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male gender ages 18-64 at least one vitiligo skin lesion measuring at least 2x2 cm in size willing and able to understand and sign informed consent able to complete study and comply with study procedures Exclusion Criteria: history of segmental vitiligo allergy to statin medications use of statin medications due to cardiac risks. use of any medications contraindicated with use of simvastatin use of topical vitiligo treatments in past 4 weeks use of laser or light-based vitiligo treatments within the past 8 weeks treatment with immunomodulating oral medications in the past 4 weeks use of statin medications in the past 8 weeks evidence of hepatic dysfunction, personal or family history of non-alcoholic steatotic hepatitis, or personal history of hepatitis evidence of renal dysfunction history of myopathy or rhabdomyolysis, or elevated baseline creatinine kinase recent history of alcohol or drug abuse history of diabetes untreated hypothyroidism other conditions that require the use of interfering topical or systemic therapy other current conditions that might interfere with study assessments such as, but not limited to, atopic dermatitis and psoriasis clinically significant abnormal findings or conditions which might, in the opinion of the Principal Investigator, interfere with study evaluations or pose a risk to subject safety during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Male

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>Sig: Simvastatin 40 mg, increased to 80 mg after 1 month if initial dose tolerated | Drug: Simvastatin<br>* Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated<br>|
| Placebo Comparator: Placebo Arm<br>Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated | Drug: Placebo<br>* Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Decrease in Vitiligo Area Scoring Index (VASI) Score | Number of participants with 33% decrease in the Vitiligo Area Scoring Index (VASI) from baseline to the last available study visit. Decrease in VASI score means improvement. Minimum value is 0, that means no vitiligo. maximum value is 100, that means 100% of the body surface area has vitiligo (total body surface area). | Assessed at baseline and final study visit, 6 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Increase in Investigator's Global Assessment Score | Increase in Investigator Global Assessment Scores of 30% or more from baseline to last available visit. Increase in score means improvement. 0% is no improvement at all. 100% is complete recovery. | Assessed at baseline and final study visit, 6 months after randomization | 
| Number of Participants Experiencing Toxicity From of High-dose Simvastatin . | The number of participants who experienced toxicity based upon monitored lab values (Liver Function Test) and patient symptoms for evidence of simvastatin toxicity | Assessed at baseline, then monthly until final study visit, six months after randomization. | 
| Change in Sentinel Patch Area | Change in percent depigmentation of sentinel patch lesion from baseline to last available study visit ( 6 months after randomization). positive numbers mean increase or worsening of sentinel patch area negative numbers mean decrease or improvement of sentinel patch area | Assessed at baseline and final study visit, 6 months after randomization | 
| Change in Quality of Life Score by Using DERMATOLOGY LIFE QUALITY INDEX (DLQI) | The aim of this questionnaire is to measure how much your skin problem has affected your life. We measured change in questionnaire score from baseline to end of study (at 6 months after randomization) of subjects randomized to treatment with simvastatin versus placebo. Change was measured as a drop in score at the end of 6 months of treatment. Minimum score is 0, maximum is 30. Higher value means worse score. | Assessed at baseline and final study visit, 6 months after randomization | 
| Number of Participants With an Increase in Patient's Global Assessment Score | Increase in Patient's Global Assessment Scores of 30% or more from baseline to last available visit Increase means improvement. minimum is 0% and maximum is 100% | Assessed at baseline and final study visit, 6 months after randomization | 
| Serum CXCL10 Levels From the First and Last Available Clinic Visits Were Measured Via ELISA | Determination of the effects of simvastatin treatment on Serum CXCL10 levels from the first and last available clinic visits were measured via ELISA in the blood of patients with vitiligo treated with simvastatin versus placebo | Assessed at baseline and final study visit, 6 months after randomization | 
| CXCR3 Expression on CD8+ T Cells | Determination of the effects of simvastatin treatment on CXCR3 expression in melanocyte-specific, autoreactive CD8+ T cells in the blood of patients with vitiligo treated with simvastatin versus placebo | Assessed prior to treatment and periodically while on treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitiligo, simvastatin