Clinical Trial of Simvastatin to Treat Generalized Vitiligo

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

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.

Study Overview

• Status: Completed
• Conditions: Vitiligo
• Intervention / Treatment: Drug: Simvastatin; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: John Harris
• Investigators: Principal Investigator: John E. Harris, MD, PhD, University of Massachusetts, Worcester

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: January 13, 2012
• First Submitted That Met QC Criteria: January 20, 2012
• First Posted (Estimate): January 25, 2012

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: October 17, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: simvastatin; vitiligo
• Additional Relevant MeSH Terms: Skin Diseases; Pigmentation Disorders; Hypopigmentation; Vitiligo; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: UM-DERM001

Drug and device information, study documents

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