Melanoma, Skin
Conditions
Keywords
quality of life
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.
Interventions
DRUGVitamin D3
4,000 IU oral vitamin D3
Sponsors
National Institutes of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vitamin D Toxicity | 2 years | serum 25(OH)D for |
| Incidence of Hypercalcemia for Vitamin D Toxicity | 2 years | Calcium levels |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Vitamin D 4,000 IU oral vitamin D3
Vitamin D3: 4,000 IU oral vitamin D3 | 18 |
| Arm B: Placebo Placebo - subjects may cross over to vitamin D treatment after placebo treatment is complete | 6 |
| Total | 24 |
Baseline characteristics
| Characteristic | Arm A: Vitamin D | Arm B: Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 12.6 | 55.8 years STANDARD_DEVIATION 5.7 | 56.1 years STANDARD_DEVIATION 10.6 |
| Gender Female | 18 Participants | 6 Participants | 24 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 18 participants | 6 participants | 24 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 18 | 0 / 6 |
| serious Total, serious adverse events | 0 / 18 | 0 / 6 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Treated With Vitamin D3 | Number of Genes Differentialy Regulated in Melanoma That Showed Changes in Expression After Vitamin D Treatment | 47 number of genes |
Primary
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.
Time frame: 2 years
Population: All subjects treated with vitamin D3.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Treated With Vitamin D3 | Number of Genes That Showed Changes in Expression After Vitamin D Treatment | 270 number of genes |
Secondary
Incidence of Hypercalcemia for Vitamin D Toxicity
Calcium levels
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients Treated With Vitamin D3 | Incidence of Hypercalcemia for Vitamin D Toxicity | 0 participants |
| Arm B: Placebo | Incidence of Hypercalcemia for Vitamin D Toxicity | 0 participants |
Secondary
Vitamin D Toxicity
serum 25(OH)D for
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients Treated With Vitamin D3 | Vitamin D Toxicity | 47.11 ng/ml | Standard Deviation 14.5 |
| Arm B: Placebo | Vitamin D Toxicity | 29.83 ng/ml | Standard Deviation 4.02 |