Vitamin D Deficiency
Conditions
Brief summary
Participants in this study will be randomized to receive either oral vitamin D pills OR ultraviolet light treatment. The investigators will compare how these two methods of raising vitamin D levels will affect cholesterol levels.
Detailed description
Potential subjects will be screened for eligibility, including serum 25(OH)D levels \<20ng/ml. Eligible subjects will be randomly assigned to receive either: 1) oral vitamin D3, 50,000 units weekly for 8 weeks or 2) narrow-band UVB radiation, 2 treatments/wk for 8 weeks. Duration of treatment will be based on skin type. After 8 weeks, 25(OH)D levels will be measured monthly. For participants with levels \<35 ng/ml, additional doses of oral vitamin D3 or UV radiation will be administered. A subset of participants from both groups will participate in a skin biopsy cohort, where skin biopsies are obtained before and after 8 weeks of treatment.
Interventions
DIETARY_SUPPLEMENTOral Vitamin D3
50,000 units orally, each week x8 weeks; supplemental doses of 50,000 units orally, each month thereafter as needed
RADIATIONUltraviolet Light
16 treatments, 2-3 times weekly over 8 weeks; initial dose 45-75 seconds, whole-body exposure except face and groin, increasing by 10% as tolerated, to a maximum of 4.5 minutes
Sponsors
Rockefeller University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Age \> 18 years 2. Vitamin D 25-OH level \< 20 ng/ml
Exclusion criteria
1. Serum calcium \> 10.5 mg/dl 2. Serum phosphorus \> 5.5 mg/dl 3. Serum parathyroid hormone (PTH) level \< 12 pg/ml 4. LDL cholesterol \> 190 mg/dl 5. History of recent acute infection (within 1 month) 6. Glomerular filtration rate(GFR) \< 60 mL/min 7. Liver Function tests indicative of liver disease (aspartate aminotransferase (AST) or alanine transferase (ALT) \> 3x ULN) 8. Current use of Vitamin D \> 400 IU/day 9. Current use of any statins, fibrates, niacin, or ezetimibe 10. Current use of any medications affecting sensitivity to UV light 11. Pregnancy (self-reported) 12. Intentional UV exposure (e.g. tanning bed use) in the last 2 weeks or planned use while participating in the study 13. history of malignancy not in remission (\> 6 months) 14. History of malignant melanoma 15. Participation in an investigational drug study within 30 days of the screening visit 16. Any medical, psychological or social condition that, in the opinion of the Investigator, would jeopardize the health or well-being of the participant during any study procedures or the integrity of the data. 17. History of any non-melanoma skin cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in LDL Cholesterol Level | baseline and 6 months or last observation carried forward (minimum 2 months) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Triglycerides | baseline 6 months or last observation carried forward (minimum 2 months) | — |
| Change in C Reactive Protein | baseline and 6 months | — |
| Change in 25(OH)D | baseline vs. 6 months | — |
| Change in Serum Calcium | baseline vs. 6 months | — |
| Change in Parathyroid Hormone (PTH) | baseline vs.6 months | — |
| Change in Total Cholesterol | baseline and 6 months or last observation carried forward (minimum 2 months) | Change in Total Cholesterol |
| Change in HDL Cholesterol | baseline and 6 months or last observation carried forward (minimum 2 months) | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gene Expression Changes in Peripheral Blood | baseline vs. 2 months | Interferon response genesets (curated by GSEA). Values are presented as the normalized enrichment score, a metric of gene upregulation (when positive) or down-regulation (when negative), normalized for gene set size. This is a useful basis for comparison for direction and degree of change between treatment groups and GSEA genesets. |
| Gene Expression Changes in Skin | baseline vs. 2 months | Interferon response genesets (curated by GSEA). Values are presented as the normalized enrichment score, a metric of gene upregulation (when positive) or down-regulation (when negative), normalized for gene set size. This is a useful basis for comparison for direction and degree of change between treatment groups and GSEA genesets. |
| Correlation Between Change in LDL Cholesterol and Change in Calcium | 2 months | The Correlation between change in LDL cholesterol and change in serum calcium |
| Correlation Between Change in LDL Cholesterol and Change in PTH | 2 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Vitamin D3 Participants will receive oral vitamin D3 50,000 units weekly for 8 weeks. If 25(OH)D levels remain \<35 ng/ml, subjects will receive additional doses of oral vitamin D.
Oral Vitamin D3: 50,000 units orally, each week x8 weeks; supplemental doses of 50,000 units orally, each month thereafter as needed | 60 |
| Ultraviolet Light Subjects will receive 16 treatments with ultraviolet light (narrow band UVB) over 8 weeks. If 25(OH)D levels remain \<35 ng/ml, subjects will receive additional doses of narrow band UVB.
Ultraviolet Light: 16 treatments, 2-3 times weekly over 8 weeks; initial dose 45-75 seconds, whole-body exposure except face and groin, increasing by 10% as tolerated, to a maximum of 4.5 minutes | 58 |
| Total | 118 |
Baseline characteristics
| Characteristic | Oral Vitamin D3 | Ultraviolet Light | Total |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 12 | 39 years STANDARD_DEVIATION 12 | 42 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 60 participants | 58 participants | 118 participants |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 65 Participants |
| Sex: Female, Male Male | 28 Participants | 25 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 60 | 21 / 58 |
| serious Total, serious adverse events | 1 / 60 | 2 / 58 |
Outcome results
Primary
Change in LDL Cholesterol Level
Time frame: baseline and 6 months or last observation carried forward (minimum 2 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in LDL Cholesterol Level | 3.2 mg/dl | Standard Deviation 18.4 |
| Ultraviolet Light | Change in LDL Cholesterol Level | 1.4 mg/dl | Standard Deviation 17.8 |
Secondary
Change in 25(OH)D
Time frame: baseline vs. 6 months
Population: Data only for those who completed 6 months of therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in 25(OH)D | 18.7 ng/ml | Standard Deviation 8 |
| Ultraviolet Light | Change in 25(OH)D | 15.6 ng/ml | Standard Deviation 8.2 |
Secondary
Change in C Reactive Protein
Time frame: baseline and 6 months
Population: Data analyzed are only for those who completed 6 months of therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in C Reactive Protein | 1.88 mg/L | Standard Deviation 6.87 |
| Ultraviolet Light | Change in C Reactive Protein | -.11 mg/L | Standard Deviation 5.1 |
Secondary
Change in HDL Cholesterol
Time frame: baseline and 6 months or last observation carried forward (minimum 2 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in HDL Cholesterol | 0.2 mg/dL | Standard Deviation 8.1 |
| Ultraviolet Light | Change in HDL Cholesterol | 0.3 mg/dL | Standard Deviation 8.4 |
Secondary
Change in Parathyroid Hormone (PTH)
Time frame: baseline vs.6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in Parathyroid Hormone (PTH) | -5 pg/mL | Standard Deviation 19 |
| Ultraviolet Light | Change in Parathyroid Hormone (PTH) | -9 pg/mL | Standard Deviation 31 |
Secondary
Change in Serum Calcium
Time frame: baseline vs. 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in Serum Calcium | .09 mg/dL | Standard Deviation 0.35 |
| Ultraviolet Light | Change in Serum Calcium | .07 mg/dL | Standard Deviation 0.29 |
Secondary
Change in Total Cholesterol
Change in Total Cholesterol
Time frame: baseline and 6 months or last observation carried forward (minimum 2 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in Total Cholesterol | 4.1 mg/dL | Standard Deviation 22 |
| Ultraviolet Light | Change in Total Cholesterol | 2.0 mg/dL | Standard Deviation 18.8 |
Secondary
Change in Triglycerides
Time frame: baseline 6 months or last observation carried forward (minimum 2 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Oral Vitamin D3 | Change in Triglycerides | 2.6 mg/dL | Standard Deviation 35.4 |
| Ultraviolet Light | Change in Triglycerides | 1.7 mg/dL | Standard Deviation 42 |
Other Pre-specified
Correlation Between Change in LDL Cholesterol and Change in Calcium
The Correlation between change in LDL cholesterol and change in serum calcium
Time frame: 2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Vitamin D3 | Correlation Between Change in LDL Cholesterol and Change in Calcium | 0.24 Pearson correlation coefficient |
| Ultraviolet Light | Correlation Between Change in LDL Cholesterol and Change in Calcium | .16 Pearson correlation coefficient |
Other Pre-specified
Correlation Between Change in LDL Cholesterol and Change in PTH
Time frame: 2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Vitamin D3 | Correlation Between Change in LDL Cholesterol and Change in PTH | -.01 Pearson correlation coefficient |
| Ultraviolet Light | Correlation Between Change in LDL Cholesterol and Change in PTH | .18 Pearson correlation coefficient |
Other Pre-specified
Gene Expression Changes in Peripheral Blood
Interferon response genesets (curated by GSEA). Values are presented as the normalized enrichment score, a metric of gene upregulation (when positive) or down-regulation (when negative), normalized for gene set size. This is a useful basis for comparison for direction and degree of change between treatment groups and GSEA genesets.
Time frame: baseline vs. 2 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Vitamin D3 | Gene Expression Changes in Peripheral Blood | Interferon-alpha response | 4.14 GSEA Normalized Enrichment Score |
| Oral Vitamin D3 | Gene Expression Changes in Peripheral Blood | Interferon-gamma response | 3.41 GSEA Normalized Enrichment Score |
| Ultraviolet Light | Gene Expression Changes in Peripheral Blood | Interferon-alpha response | -4.05 GSEA Normalized Enrichment Score |
| Ultraviolet Light | Gene Expression Changes in Peripheral Blood | Interferon-gamma response | -4.86 GSEA Normalized Enrichment Score |
Other Pre-specified
Gene Expression Changes in Skin
Interferon response genesets (curated by GSEA). Values are presented as the normalized enrichment score, a metric of gene upregulation (when positive) or down-regulation (when negative), normalized for gene set size. This is a useful basis for comparison for direction and degree of change between treatment groups and GSEA genesets.
Time frame: baseline vs. 2 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Oral Vitamin D3 | Gene Expression Changes in Skin | Interferon-alpha response | 2.08 GSEA Normalized Enrichment Score |
| Oral Vitamin D3 | Gene Expression Changes in Skin | Interferon-gamma response | 2.12 GSEA Normalized Enrichment Score |
| Ultraviolet Light | Gene Expression Changes in Skin | Interferon-alpha response | -2.43 GSEA Normalized Enrichment Score |
| Ultraviolet Light | Gene Expression Changes in Skin | Interferon-gamma response | -2.00 GSEA Normalized Enrichment Score |