Vitamin D Deficiency
Conditions
Keywords
Vitamin D, FGF23, FGF-23, Phosphate
Brief summary
Fibroblast growth factor 23 (FGF23) is a new hormone which controls phosphate and vitamin D levels in humans. Excess FGF23 is associated with an increased risk of death in patients with chronic kidney disease. In this study the investigators are investigating the effects of different forms of vitamin D on FGF23 levels in the blood in order to increase our understanding of how this important hormone works.
Detailed description
Fibroblast growth factor 23 (FGF23) is a novel hormone involved in phosphate and vitamin D physiology. X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), and tumor induced osteomalacia (TIO) are 3 rare diseases characterized by rickets/osteomalacia, fractures, and hypophosphatemia secondary to renal phosphate wasting and inappropriately low levels of activated vitamin D (calcitriol), which are caused by excess amounts of or mutated FGF23. FGF23 excess also occurs in renal failure, where elevated FGF23 levels predict increased mortality. Thus, abnormal FGF23 appears to be central to both rare and common diseases. While FGF23 appears to be regulated by vitamin D, dietary and serum phosphate, much is still unknown. The effects of different forms of vitamin D on FGF23 stimulation are not well characterized. Similarly, any racial differences in the regulation of FGF23 by vitamin D have not been investigated. To address these knowledge deficits, we will randomize 52 vitamin D deficient (25OHD \< or = 24 ng/mL by LC/MS) Caucasian and African-American men and women to treatment with either dietary vitamin D or activated vitamin D for 12 weeks. Our primary endpoint will be the change in FGF23 with dietary versus activated vitamin D.
Interventions
DIETARY_SUPPLEMENTErgocalciferol
Ergocalciferol 50000 international units by mouth weekly for 12 weeks
DIETARY_SUPPLEMENTCalcitriol
Calcitriol 0.5 mcg by mouth daily for 12 weeks
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 45 yrs * Serum 25OHD \< 24 ng/mL by liquid chromatography/mass spectroscopy * At least 1 menses in the last 3 months (females) and normal serum testosterone (males) * African-American or Caucasian race
Exclusion criteria
* Significant cardiac, hepatic, oncologic, or psychiatric disease * History of malabsorption, kidney stones, or recent alcohol excess/abuse * Use of medications known to affect serum phosphate levels including phosphate-binding antacids, sodium etidronate, calcitonin, excessive doses of vitamin D (\> 1000 units per day), excessive doses of vitamin A (\> 20,000 units/day), calcitriol, growth hormone, or anti-convulsants * Use of thiazide diuretics or cholestyramine * Serum calcium \< 8 or \> 11 mg/dL, creatinine \> 1.5 mg/dL, or Hgb \< 11 gm/dL * Serum glucose \>140mg/dL * Liver function tests \> 2 times the upper limit of normal * TSH \< 0.1 or \> 7 uU/mL * WBC \< 2,000 or \> 15,000/cmm * Platelet count \< 100,000 or \> 500,000/cum * Hormone replacement therapy (however, oral contraceptives are allowed) or testosterone use * Urine beta-hCG positive (females) * Serum phosphate \> 4.6 mg/dL * Allergy to vitamin D
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in FGF23 levels | 12 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in serum phosphate | 12 weeks |
| Change in urinary phosphate | 12 weeks |
| Change in serum calcium | 12 weeks |
Countries
United States
Outcome results
None listed