Different Vitamin D Preparations & FGF23 in Humans

Sponsor

Massachusetts General Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00957879

Collaborator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Enrollment

Location

Arms

Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency	Dietary Supplement: Ergocalciferol Dietary Supplement: Calcitriol	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Official Title:

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

Study Start Date :

May 1, 2009

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in FGF23 levels [12 weeks]

Secondary Outcome Measures

Change in serum phosphate [12 weeks]
Change in urinary phosphate [12 weeks]
Change in serum calcium [12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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