Clinical Trial of Simvastatin to Treat Generalized Vitiligo

• ClinicalTrials.gov Identifier: NCT01517893
• Recruitment Status: Completed
• First Posted: January 25, 2012
• Results First Posted: March 12, 2015
• Last Update Posted: November 14, 2018
• Sponsor: John Harris
• Information provided by (Responsible Party): John Harris, University of Massachusetts, Worcester

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vitiligo	Drug: Simvastatin; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase-II, Randomized, Placebo-controlled Trial of Simvastatin in Generalized Vitiligo
• Study Start Date: January 2012
• Actual Primary Completion Date: December 2013
• Actual Study Completion Date: December 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With a Decrease in Vitiligo Area Scoring Index (VASI) Score [ Time Frame: 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 :

1. Number of Participants With Increase in Investigator's Global Assessment Score [ Time Frame: 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.

2. Number of Participants Experiencing Toxicity From of High-dose Simvastatin . [ Time Frame: 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
3. Change in Sentinel Patch Area [ Time Frame: 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

4. Change in Quality of Life Score by Using DERMATOLOGY LIFE QUALITY INDEX (DLQI) [ Time Frame: 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.

5. Number of Participants With an Increase in Patient's Global Assessment Score [ Time Frame: 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%
6. Serum CXCL10 Levels From the First and Last Available Clinic Visits Were Measured Via ELISA [ Time Frame: 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
7. CXCR3 Expression on CD8+ T Cells [ Time Frame: 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Massachusetts

University of Massachusetts Medical School Clinical Research Center

Worcester, Massachusetts, United States, 01655

Sponsors and Collaborators

John Harris

Investigators

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

More Information

• Responsible Party: John Harris, Principal Investigator, University of Massachusetts, Worcester
• ClinicalTrials.gov Identifier: NCT01517893
• Other Study ID Numbers: UM-DERM001
• First Posted: January 25, 2012
• Results First Posted: March 12, 2015
• Last Update Posted: November 14, 2018
• Last Verified: October 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by John Harris, University of Massachusetts, Worcester:

vitiligo; simvastatin

Additional relevant MeSH terms:

Vitiligo; Hypopigmentation; Pigmentation Disorders; Skin Diseases; Simvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors