Clinical Trial of Simvastatin to Treat Generalized Vitiligo

Phase 2

Completed

Conditions: Vitiligo

Interventions: Drug: Placebo
Drug: Simvastatin

Registration Number: NCT01517893

Lead Sponsor: John Harris

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 15

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Arm	Placebo	Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated
Intervention arm	Simvastatin	Sig: Simvastatin 40 mg, increased to 80 mg after 1 month if initial dose tolerated

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Decrease in Vitiligo Area Scoring Index (VASI) Score	Assessed at baseline and final study visit, 6 months after randomization	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).

Secondary Outcome Measures

Name	Time	Method
Change in Sentinel Patch Area	Assessed at baseline and final study visit, 6 months after randomization	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
Serum CXCL10 Levels From the First and Last Available Clinic Visits Were Measured Via ELISA	Assessed at baseline and final study visit, 6 months after randomization	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
Number of Participants With Increase in Investigator's Global Assessment Score	Assessed at baseline and final study visit, 6 months after randomization	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.
Change in Quality of Life Score by Using DERMATOLOGY LIFE QUALITY INDEX (DLQI)	Assessed at baseline and final study visit, 6 months after randomization	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.
Number of Participants With an Increase in Patient's Global Assessment Score	Assessed at baseline and final study visit, 6 months after randomization	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%
Number of Participants Experiencing Toxicity From of High-dose Simvastatin .	Assessed at baseline, then monthly until final study visit, six months after randomization.	The number of participants who experienced toxicity based upon monitored lab values (Liver Function Test) and patient symptoms for evidence of simvastatin toxicity
CXCR3 Expression on CD8+ T Cells	Assessed prior to treatment and periodically while on treatment	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