Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment
研究概览
简要总结
The purpose of this study is to determine the signaling pathways and changes in gene expression in melanocytes of subjects with a history of non-melanoma skin cancer who are exposed to oral vitamin D. If vitamin D is found to inhibit a signaling pathway involved in the development of melanoma such as BRAF, a protein involved in cell proliferation, then oral vitamin D could be explored further as a chemoprevention for melanoma skin cancer.
详细描述
Background:
Vitamin D is an important hormone that has multiple genetic effects in different tissue types that are mediated by signaling through the vitamin D receptor.
Recent studies have shown that vitamin D signaling results in decreased innate immunity and increased adaptive immunity.
Multiple epidemiologic studies have suggested that vitamin D may play a role in decreasing the risk of developing multiple types of cancer, including skin cancer.
In the context of the relative success of novel immune-related therapies including PD1 inhibitors, which improves immuno-surveillance, and ipilimumab, which suppresses T cell response, there is increased promise for treatment strategies that activate innate immunity. This led us to ask the question of whether vitamin D could increase immune surveillance for melanoma via increased activity of the adaptive immune system.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18 - 75
- •White race/ethnicity
- •With history of non-melanoma skin cancer
- •Has 12-16 moles upon skin examination
- •Consents to 6-12 moles biopsies over 2-3 clinic visits (2-4 months)
- •Consents to ingesting oral vitamin D3 or placebo daily for 2-4 months
- •Consents to abstaining from other multivitamins during study
- •Consents to research use of their tissue and blood samples
- •Agrees to apply a sunscreen of SPF 45 during study -
排除标准
- •History or current evidence of hyperparathyroidism, hypercalcemia, renal calculi, or other renal disease.
- •History or current evidence of malabsorptive illnesses, such as IBD, or liver disease that would impair uptake or metabolism of vitamin D.
- •History or current evidence of hyperthyroidism that would increase metabolism of vitamin D.
- •History or current evidence of immunosuppression (cancer, autoimmune disease) or taking immunosuppressive drugs.
- •Currently taking medications that would affect metabolism of vitamin D (anticonvulsants, corticosteroids, H2-receptor antagonists).
- •Currently taking medications that predispose to hypercalcemia (digoxin, lithium, thiazide diuretics) or other electrolyte disturbances (aluminum hydroxide)
研究组 & 干预措施
Arm A: Vitamin D
4,000 IU oral vitamin D3
干预措施: Vitamin D3 (Drug)
Arm B: Placebo + Vitamin D
Placebo + 4000 IU oral Vitamin D3
干预措施: placebo and vitamin D (Drug)
结局指标
主要结局
Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment
时间窗: 2 years
We utilized a prior gene expression study that compared malignant melanoma cells to benign nevi (moles) and identified over 2300 genes that were differentially regulated in melanoma compared to benign nevi. There were approximately 270 genes in our data set that showed changes in expression after vitamin D treatment. We wish to identify overlap between these two groups.
Number of Genes That Showed Changes in Expression After Vitamin D Treatment
时间窗: 2 years
Normal cells have a complex series of molecular signals that allow communication between cells and to the cell nucleus. These signals work together to control one or more cell functions, such as cell division or cell death. Abnormal signaling activity caused by changes in gene expression can lead to cancer. An understanding of abnormal signaling, both in the tumor and in normal tissues, may lead to new therapies in cancer patients. We wish to identify changes in molecular signaling that occur in the development of melanoma that might be suppressed in benign nevi (moles) in response to vitamin D supplementation.
次要结局
- Vitamin D Toxicity(2 years)
- Incidence of Hypercalcemia for Vitamin D Toxicity(2 years)
研究者
Jean Yuh Tang
Associate Professor of Dermatology
Stanford University