Clinical trial NCT01477463: Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers
Official title: Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Melanoma, Skin
Keywords: quality of life
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2011-11-22
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18 - 75
2. Female
3. White race/ethnicity
4. With history of non-melanoma skin cancer
5. Has 12-16 moles upon skin examination
6. Consents to 6-12 moles biopsies over 2-3 clinic visits (2-4 months)
7. Consents to ingesting oral vitamin D3 or placebo daily for 2-4 months
8. Consents to abstaining from other multivitamins during study
9. Consents to research use of their tissue and blood samples
10. Agrees to apply a sunscreen of SPF 45 during study -

Exclusion Criteria:

1. History or current evidence of hyperparathyroidism, hypercalcemia, renal calculi, or other renal disease.
2. History or current evidence of malabsorptive illnesses, such as IBD, or liver disease that would impair uptake or metabolism of vitamin D.
3. History or current evidence of hyperthyroidism that would increase metabolism of vitamin D.
4. History or current evidence of immunosuppression (cancer, autoimmune disease) or taking immunosuppressive drugs.
5. Currently taking medications that would affect metabolism of vitamin D (anticonvulsants, corticosteroids, H2-receptor antagonists).
6. Currently taking medications that predispose to hypercalcemia (digoxin, lithium, thiazide diuretics) or other electrolyte disturbances (aluminum hydroxide)
7. Pregnancy

Primary outcomes:
measure: Number of Genes That Showed Changes in Expression After Vitamin D Treatment
timeFrame: 2 years
measure: Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment
timeFrame: 2 years
Secondary outcomes:
measure: Vitamin D Toxicity
timeFrame: 2 years
measure: Incidence of Hypercalcemia for Vitamin D Toxicity
timeFrame: 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University Cancer Institute
state: California
Study officials:
affiliation: Stanford University
name: Jean Y Tang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: