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

This study has been completed.
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Jean Yuh Tang, Stanford University
ClinicalTrials.gov Identifier:
NCT01477463
First received: November 17, 2011
Last updated: October 31, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention
Melanoma, Skin
Drug: Vitamin D3
Drug: placebo and vitamin D

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pilot Trial to Evaluate the Effect of Vitamin D on Melanocyte Biomarkers

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Number of Genes That Showed Changes in Expression After Vitamin D Treatment [ Time Frame: 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.

  • Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment [ Time Frame: 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.


Secondary Outcome Measures:
  • Vitamin D Toxicity [ Time Frame: 2 years ]
    serum 25(OH)D for

  • Incidence of Hypercalcemia for Vitamin D Toxicity [ Time Frame: 2 years ]
    Calcium levels


Enrollment: 24
Study Start Date: September 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Vitamin D
4,000 IU oral vitamin D3
Drug: Vitamin D3
4,000 IU oral vitamin D3
Other Name: 25-hydroxy D3
Experimental: Arm B: Placebo + Vitamin D
Placebo + 4000 IU oral Vitamin D3
Drug: placebo and vitamin D
Other Name: inactive tablet and 25-hydroxy D3

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

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01477463

Locations
United States, California
Stanford University Cancer Institute
Palo Alto, California, United States, 94305
Sponsors and Collaborators
Stanford University
National Institutes of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Investigators
Principal Investigator: Jean Y Tang, MD, PhD Stanford University
  More Information

Responsible Party: Jean Yuh Tang, Associate Professor of Dermatology, Stanford University
ClinicalTrials.gov Identifier: NCT01477463     History of Changes
Other Study ID Numbers: SKIN0010  SU-10272011-8570  IRB-22207  5K23AR056736 
Study First Received: November 17, 2011
Results First Received: June 30, 2016
Last Updated: October 31, 2016
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Results will be submitted to scientific journal for publication.

Keywords provided by Stanford University:
quality of life

Additional relevant MeSH terms:
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on February 23, 2017