Metformin as a Novel Treatment for Vitiligo by Targeting CD8+ T Cell Metabolism
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Define the different populations of cells by flow cytometry
研究概览
简要总结
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.
详细描述
Metformin modulates metabolism in multiple cell types and is currently used to reduce glucose levels and insulin resistance in diabetic patients. Bae et al. 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label (unmasked)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults 18 years and older with stable vitiligo
- •Stable vitiligo is defined as no new spots of depigmentation or expansion of any existing spots for one year;
- •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;
排除标准
- •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.
研究组 & 干预措施
Oral Metformin
Treatment with metformin will be started at 500 mg twice daily and increased to 1000 mg twice daily only after they have tolerated the treatment.
干预措施: Metformin Hydrochloride (Drug)
结局指标
主要结局
Define the different populations of cells by flow cytometry
时间窗: 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.
次要结局
- Define the inflammatory conditions in the lesions(Week 24)
- 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)
- Vitiligo Area Scoring Index 50% improvement (VASI50) after 6 months of treatment(Week 24)
- Face-Vitiligo Area Scoring Index 50% improvement (F-VASI50) after 6 months of treatment(Week 24)
研究者
John Harris
Chair
University of Massachusetts, Worcester