Clinical trial NCT00957879: Different Vitamin D Preparations & FGF23 in Humans
Official title: Effect of Different Vitamin D Preparations on Circulating FGF23 Levels in Vitamin D Deficient Caucasian and African-American Men and Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D Deficiency
Keywords: Vitamin D
FGF23
FGF-23
Phosphate
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-08-13
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in FGF23 levels
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in serum phosphate
timeFrame: 12 weeks
measure: Change in urinary phosphate
timeFrame: 12 weeks
measure: Change in serum calcium
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Sherri-Ann M Burnett-Bowie, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burnett SM, Gunawardene SC, Bringhurst FR, Juppner H, Lee H, Finkelstein JS. Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res. 2006 Aug;21(8):1187-96. doi: 10.1359/jbmr.060507.
citation: Bhan I, Shah A, Holmes J, Isakova T, Gutierrez O, Burnett SM, Juppner H, Wolf M. Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'? Kidney Int. 2006 Oct;70(8):1486-94. doi: 10.1038/sj.ki.5001788. Epub 2006 Aug 30.
citation: Burnett-Bowie SM, Mendoza N, Leder BZ. Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men. Bone. 2007 Apr;40(4):913-8. doi: 10.1016/j.bone.2006.10.016. Epub 2006 Dec 8.
citation: Burnett-Bowie SM, Henao MP, Dere ME, Lee H, Leder BZ. Effects of hPTH(1-34) infusion on circulating serum phosphate, 1,25-dihydroxyvitamin D, and FGF23 levels in healthy men. J Bone Miner Res. 2009 Oct;24(10):1681-5. doi: 10.1359/jbmr.090406.