Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers

Not Applicable

Completed

Conditions: Melanoma, Skin

Interventions: Drug: placebo and vitamin D
Drug: Vitamin D3

Registration Number: NCT01477463

Lead Sponsor: Stanford University

Brief Summary: 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.

Detailed Description: 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.

Prior studies performed by our group and others have suggested that vitamin D may play a role in decreasing melanoma risk. An epidemiologic study from the Women's Health Initiative showed that women with a prior history of NMSC who received calcium and vitamin D supplementation had a lower risk of subsequently developing melanoma. At the same time, women with a lower serum vitamin D level had a higher risk of developing melanoma. Furthermore, a recent clinical study showed that vitamin D supplementation increases serum vitamin D levels and ultimately results in increased vitamin D receptor signaling in benign nevi.

Taken together, this findings led us to ask whether oral vitamin D supplementation could impact immune signaling in benign nevi and potentially underpin a theoretical chemo-preventive role for vitamin D in melanoma.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 24

Inclusion Criteria

Age 18 - 75
Female
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 -

Exclusion Criteria

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)
Pregnancy

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm B: Placebo + Vitamin D	placebo and vitamin D	Placebo + 4000 IU oral Vitamin D3
Arm A: Vitamin D	Vitamin D3	4,000 IU oral vitamin D3

Primary Outcome Measures

Name	Time	Method
Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment	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	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.

Secondary Outcome Measures