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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma, Skin
• Intervention / Treatment: Drug: Vitamin D3; Drug: placebo and vitamin D

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Vitamin D; 4,000 IU oral vitamin D3	Drug: Vitamin D3; 4,000 IU oral vitamin D3; Other Names: 25-hydroxy D3
Experimental: Arm B: Placebo + Vitamin D; Placebo + 4000 IU oral Vitamin D3	Drug: placebo and vitamin D; Other Names: inactive tablet and 25-hydroxy D3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Genes That Showed Changes in Expression After Vitamin D Treatment	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.	2 years
Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment	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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D Toxicity	serum 25(OH)D for	2 years
Incidence of Hypercalcemia for Vitamin D Toxicity	Calcium levels	2 years

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Jean Y Tang, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: November 17, 2011
• First Submitted That Met QC Criteria: November 17, 2011
• First Posted (Estimate): November 22, 2011

Study Record Updates

• Last Update Posted (Estimate): December 23, 2016
• Last Update Submitted That Met QC Criteria: October 31, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: quality of life
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: SKIN0010; SU-10272011-8570 (Other Identifier: Stanford University); IRB-22207 (Other Identifier: Stanford University); 5K23AR056736 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Results will be submitted to scientific journal for publication.