Different Vitamin D Preparations & FGF23 in Humans

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Different Vitamin D Preparations on Circulating FGF23 Levels in Vitamin D Deficient Caucasian and African-American Men and Women

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Ergocalciferol
* Dietary Supplement: Calcitriol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ergocalciferol<br>Weekly ergocalciferol for 12 weeks | Dietary Supplement: Ergocalciferol<br>* Ergocalciferol 50000 international units by mouth weekly for 12 weeks<br>|
| Active Comparator: calcitriol<br>Daily calcitriol for 12 weeks | Dietary Supplement: Calcitriol<br>* Calcitriol 0.5 mcg by mouth daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FGF23 levels |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum phosphate |  | 12 weeks | 
| Change in urinary phosphate |  | 12 weeks | 
| Change in serum calcium |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, FGF23, FGF-23, Phosphate