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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention arm | Experimental | Sig: Simvastatin 40 mg, increased to 80 mg after 1 month if initial dose tolerated |
|
| Placebo Arm | Placebo Comparator | Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin | Drug | Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John E. Harris, MD, PhD | University of Massachusetts, Worcester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Massachusetts Medical School Clinical Research Center | Worcester | Massachusetts | 01655 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Intervention Arm | Sig: Simvastatin 40 mg, increased to 80 mg after 1 month if initial dose tolerated Simvastatin: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
| FG001 | Placebo Arm | Placebo: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Intervention Arm | Sig: Simvastatin 40 mg, increased to 80 mg after 1 month if initial dose tolerated Simvastatin: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
| BG001 | Placebo Arm |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Overall number of participants for intervention (5) differs from enrollment (8) due to withdraw of 3 participants on intervention arm. | Posted | Count of Participants | Participants | Assessed at baseline and final study visit, 6 months after randomization |
|
6 months (baseline to end of treatment)
Safety lab values and questionnaires collected for outcomes.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Intervention Arm | Sig: Simvastatin 40 mg, increased to 80 mg after 1 month if initial dose tolerated Simvastatin: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Burn | Skin and subcutaneous tissue disorders | Systematic Assessment | Sustained at work, unrelated |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
The following outcome measures were abandoned: 1.Decrease in CXCR3 exp. on CD8 positive T-Cells, 2.Corr. Among Var. Outcome Measures for Vitiligo: procedures not performed/no data collected due to strength of prior outcomes & budget limitation.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John E. Harris, MD, PhD | University of Massachusetts Medical School | 508-856-1982 | john.harris@umassmed.edu |
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| ID | Term |
|---|---|
| D014820 | Vitiligo |
| ID | Term |
|---|---|
| D017496 | Hypopigmentation |
| D010859 | Pigmentation Disorders |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Placebo | Drug | Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
|
| 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 |
Placebo: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Vitiligo area scoring index | The vitiligo area scoring index (VASI) is a measure of the surface area affected by vitiligo in a given research subject. It ranges from 0% (no vitiligo) to 100% (complete depigmentation of the entire body surface area). In terms of treatment, a decrease in VASI is desirable as it indicates less surface area affected by vitiligo. The score represents an estimate made by the investigators, based on the approximation that one "hand unit," is roughly equivalent to 1% of the body surface area. | Mean | Full Range | percentage |
|
| OG001 | Placebo Arm | Placebo: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated |
|
|
| Secondary | 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. | For placebo arm, only 6 out of 7 participants reported data. | Posted | Count of Participants | Participants | Assessed at baseline and final study visit, 6 months after randomization |
|
|
|
| Secondary | 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 | Posted | Count of Participants | Participants | Assessed at baseline, then monthly until final study visit, six months after randomization. |
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | cm2 | Assessed at baseline and final study visit, 6 months after randomization |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | units on a scale | Assessed at baseline and final study visit, 6 months after randomization |
|
|
|
| Secondary | 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% | Placebo arm reports 6 instead of enrolled 7 due to failure of participant to complete assessment. | Posted | Count of Participants | Participants | Assessed at baseline and final study visit, 6 months after randomization |
|
|
|
| Secondary | 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 | Serum CXCL10 levels from the first and last available clinic visits were measured via ELISA. The mean and SEM are reported here. One participant in intervention group was not included because participant withdrew before a second CXCL10 level was obtained. Other withdrawn participants were included, using the CXCL10 from their final visits. | Posted | Mean | Standard Error | Fold change of baseline CXCL10 level | Assessed at baseline and final study visit, 6 months after randomization |
|
|
|
| Secondary | 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 | No data collected as this outcome was abandoned due to budget constraints and strength of other study results. | Posted | Assessed prior to treatment and periodically while on treatment |
|
|
| 1 |
| 8 |
| 4 |
| 8 |
| EG001 | Placebo Arm | Placebo: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated | 0 | 7 | 4 | 7 |
|
| leg twinge | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| tinnitus | Ear and labyrinth disorders | Systematic Assessment |
|
| flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| stool odor | Gastrointestinal disorders | Systematic Assessment |
|
| pulled muscle | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| arthrlagia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| URI symptoms | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| xerosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| urine color change | Renal and urinary disorders | Systematic Assessment |
|
| sleep disturbance | Nervous system disorders | Systematic Assessment |
|
| dental infection | Infections and infestations | Systematic Assessment |
|
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| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |