Different Vitamin D Preparations & FGF23 in Humans

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

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.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency
• Intervention / Treatment: Dietary supplement: Ergocalciferol; Dietary supplement: Calcitriol

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ergocalciferol; Weekly ergocalciferol for 12 weeks	Dietary supplement: Ergocalciferol; Ergocalciferol 50000 international units by mouth weekly for 12 weeks
Active Comparator: calcitriol; Daily calcitriol for 12 weeks	Dietary supplement: Calcitriol; Calcitriol 0.5 mcg by mouth daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in FGF23 levels	12 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Sherri-Ann M Burnett-Bowie, MD, MPH, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: August 11, 2009
• First Submitted That Met QC Criteria: August 12, 2009
• First Posted (Estimate): August 13, 2009

Study Record Updates

• Last Update Posted (Estimate): April 19, 2012
• Last Update Submitted That Met QC Criteria: April 18, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Vitamin D; FGF-23; FGF23; Phosphate
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Vitamin D; Ergocalciferols; Calcitriol
• Other Study ID Numbers: 2009P000567; K23DK073356 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No