Vitiligo
Conditions
Keywords
vitiligo, metformin, systemic treatment, stable vitiligo, segmental vitiligo, non-segmental vitiligo
Brief summary
Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. The investigators hypothesize that oral metformin can regulate the metabolism of CD8+ T cells, reduce their cytotoxic activity and thus serve as a novel treatment for vitiligo.
Detailed description
Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. It has been reported that the use of metformin correlated with a lower risk of developing vitiligo, suggesting that metformin could potentially mitigate the disease. The investigators found that treating mouse T cells with metformin during activation reduced their mitochondrial respiration and proliferation, while mice treated with metformin reversed their vitiligo. Therefore, the investigators hypothesize that regulation of CD8+ T cell metabolism in vitiligo patients by metformin will reduce their proliferation and cytotoxic activity, resulting in skin repigmentation and thus serve as a novel treatment. The investigators plan to treat approximately 30 subjects with stable vitiligo. Metformin is FDA-approved for use with dosing from 500-2000 mg/day. It has a rare risk of lactic acidosis, which can be meaningful in patients with risk factors such as renal insufficiency. This risk is directly proportional to the dose given; therefore, participants will be started at a lower dose (500 mg twice daily) with follow-up to monitor any arising symptoms. Per current clinical recommendations, participants will only be increased to higher-dose metformin (1000 mg twice daily) if the initial dose is tolerated.
Interventions
DRUGMetformin Hydrochloride
Consistent with previous studies and clinical recommendations, subjects will initiate treatment at metformin 500 mg twice daily and increase to 1000 mg twice daily only after they have tolerated the treatment (details below). Study Visit 1 (Week 1) - Study Visit 2 (Week 2) Subjects will be directed to take metformin 500 mg twice daily. Study Visit 2 (Week 2) - Study Visit 5 (Week 24) If initial metformin dose is tolerated, subjects will be directed to increase the dose to 1000 mg by mouth twice daily for the remainder of the study.
Sponsors
University of Massachusetts, Worcester
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label (unmasked)
Intervention model description
Open-label (unmasked) study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults 18 years - 100 years of age with stable vitiligo * Stable vitiligo is defined as no new spots of depigmentation or expansion of any existing spots for one year; * Total body surface area BSA \>/= 1% * Facial body surface area BSA \>/= 0.25% * Willingness to participate in the study; * Willingness to undergo suction blistering; * Non-English speaking adults may be enrolled with the assistance of an interpreter and the use of an IRB-approved short form in the subject's language; * Informed consent document signed by the subject;
Exclusion criteria
* Adults unable to consent (adults lacking capacity); * Active vitiligo defined by presence of confetti lesions, trichrome lesions, and Koebner's phenomenon; * Individuals who are not yet adults (infants, children, teenagers); * Pregnant women and/or breastfeeding, or those who have recently delivered a baby within the past 6 months; * Prisoners; * Systemic immunosuppressive medication (oral corticosteroids) within prior 4 weeks; * Topical steroids within the prior 2 weeks; * Currently undergoing UVB light therapy or history of light therapy within the past 8 weeks; * Unable to return for follow-up visits; * Enrolled in a clinical study of any other investigational drug or device; * Diabetes, liver disease, or kidney disease; * Hypoglycemia as defined by fasting blood glucose \<70 mg/dL assessed at a fasting study visit; * Prescription medication or cosmetics containing: retinoids, glycolic acid, salicylic acid, or any other remedies that might affect the healing process. Non-medicated moisturizers are allowed. If the person is unsure, they can bring in any products for our review; * Self-reported history of chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance as judged by the investigator; * Any other condition or laboratory value that would, in the professional opinion of the investigators, potentially affect the subject's response or the integrity of the data or would pose an unacceptable risk to the subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Define the different populations of cells by flow cytometry | Week 24 | Determine any change in the subpopulations of CD8+ T cells using CD69 and CD103 for Trm and CD122 (IL15Rb chain) as a marker for long-lived Trm; CD44, CD62L, and CD127 for central and effector memory T cells; and CXCR3 to indicate trafficking of CD8+ T cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Define the inflammatory conditions in the lesions | Week 24 | Protein biomarker discovery using Olink® proteomics technology platform (inflammation panel) |
| Measure the abundance of metabolites with untargeted metabolomics in the blister fluid and cells from non-lesional and lesional areas, and in plasma | Week 24 | Liquid chromatography-mass spectrometry |
| Vitiligo Area Scoring Index 50% improvement (VASI50) after 6 months of treatment | Week 24 | Assess VASI at baseline and after 3 months of starting treatment. |
| Face-Vitiligo Area Scoring Index 50% improvement (F-VASI50) after 6 months of treatment | Week 24 | Assess facial VASI at baseline and after 6 months of starting treatment. |
Countries
United States
Outcome results
None listed