Different Vitamin D Preparations & FGF23 in Humans

Vitamin D Deficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00957879
• Other study ID #: 2009P000567
• Secondary ID: K23DK073356
• Status: Completed
• Phase: N/A
• First received: August 11, 2009
• Last updated: April 18, 2012
• Start date: May 2009
• Est. completion date: March 2011

Study information

• Verified date: April 2012
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: March 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Vitamin D Deficiency

Intervention

Dietary Supplement:
• Ergocalciferol
Ergocalciferol 50000 international units by mouth weekly for 12 weeks
• Calcitriol
Calcitriol 0.5 mcg by mouth daily for 12 weeks

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Bhan I, Shah A, Holmes J, Isakova T, Gutierrez O, Burnett SM, Jüppner H, Wolf M. Post-transplant hypophosphatemia: Tertiary 'Hyper-Phosphatoninism'? Kidney Int. 2006 Oct;70(8):1486-94. Epub 2006 Aug 30. — View Citation

Burnett SM, Gunawardene SC, Bringhurst FR, Jüppner 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. — View 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. — View 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. Epub 2006 Dec 8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in FGF23 levels		12 weeks	No
Secondary	Change in serum phosphate		12 weeks	No
Secondary	Change in urinary phosphate		12 weeks	No
Secondary	Change in serum calcium		12 weeks	Yes