Different Vitamin D Preparations & FGF23 in Humans

Mass General Brigham

Status

Completed

Conditions

Vitamin D Deficiency

Treatments

Dietary Supplement: Calcitriol

Dietary Supplement: Ergocalciferol

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00957879

2009P000567

K23DK073356 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

42 patients

Sex

All

Ages

18 to 45 years old

Volunteers

Accepts Healthy Volunteers

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