Vitiligo
Conditions
Keywords
vitiligo, simvastatin
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.
Interventions
DRUGSimvastatin
Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated
DRUGPlacebo
Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated
Sponsors
John Harris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 64 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 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. |
| 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 |
| 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 |
| 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% |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 | 8 |
| Placebo Arm Placebo: Sig: 40 mg PO daily for 1 month, increased to 80 mg PO daily for 5 months if low dose tolerated | 7 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Intervention Arm | Placebo Arm | Total |
|---|---|---|---|
| Age, Continuous | 43.9 years | 39 years | 41.6 years |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
| Vitiligo area scoring index | 14.81 percentage | 23.09 percentage | 19.23 percentage |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 4 / 7 |
| serious Total, serious adverse events | 1 / 8 | 0 / 7 |
Outcome results
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).
Time frame: Assessed at baseline and final study visit, 6 months after randomization
Population: Overall number of participants for intervention (5) differs from enrollment (8) due to withdraw of 3 participants on intervention arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Arm | Number of Participants With a Decrease in Vitiligo Area Scoring Index (VASI) Score | 0 Participants |
| Placebo Arm | Number of Participants With a Decrease in Vitiligo Area Scoring Index (VASI) Score | 0 Participants |
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.
Time frame: Assessed at baseline and final study visit, 6 months after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Arm | Change in Quality of Life Score by Using DERMATOLOGY LIFE QUALITY INDEX (DLQI) | 3.4 units on a scale | Standard Deviation 4.159326869 |
| Placebo Arm | Change in Quality of Life Score by Using DERMATOLOGY LIFE QUALITY INDEX (DLQI) | 2.285714286 units on a scale | Standard Deviation 2.690370837 |
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
Time frame: Assessed at baseline and final study visit, 6 months after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Arm | Change in Sentinel Patch Area | -0.2272 cm2 | Standard Deviation 3.463 |
| Placebo Arm | Change in Sentinel Patch Area | 3.8571 cm2 | Standard Deviation 9.17 |
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
Time frame: Assessed prior to treatment and periodically while on treatment
Population: No data collected as this outcome was abandoned due to budget constraints and strength of other study results.
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
Time frame: Assessed at baseline, then monthly until final study visit, six months after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Arm | Number of Participants Experiencing Toxicity From of High-dose Simvastatin . | 0 Participants |
| Placebo Arm | Number of Participants Experiencing Toxicity From of High-dose Simvastatin . | 0 Participants |
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%
Time frame: Assessed at baseline and final study visit, 6 months after randomization
Population: Placebo arm reports 6 instead of enrolled 7 due to failure of participant to complete assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Arm | Number of Participants With an Increase in Patient's Global Assessment Score | 0 Participants |
| Placebo Arm | Number of Participants With an Increase in Patient's Global Assessment Score | 1 Participants |
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.
Time frame: Assessed at baseline and final study visit, 6 months after randomization
Population: For placebo arm, only 6 out of 7 participants reported data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention Arm | Number of Participants With Increase in Investigator's Global Assessment Score | 1 Participants |
| Placebo Arm | Number of Participants With Increase in Investigator's Global Assessment Score | 0 Participants |
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
Time frame: Assessed at baseline and final study visit, 6 months after randomization
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention Arm | Serum CXCL10 Levels From the First and Last Available Clinic Visits Were Measured Via ELISA | 0.9148 Fold change of baseline CXCL10 level | Standard Error 0.263 |
| Placebo Arm | Serum CXCL10 Levels From the First and Last Available Clinic Visits Were Measured Via ELISA | 0.6176 Fold change of baseline CXCL10 level | Standard Error 0.1685 |