Vitamin D Deficiency, Insulin Resistance and FGF-23

This study has been completed.
Sponsor:
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00491322
First received: June 22, 2007
Last updated: March 26, 2008
Last verified: March 2008

June 22, 2007
March 26, 2008
May 2006
February 2008   (final data collection date for primary outcome measure)
Change in insulin resistance, insulin secretion, and FGF-23 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in insulin resistance, insulin secretion, and FGF-23 [ Time Frame: 12 weeks ]
Complete list of historical versions of study NCT00491322 on ClinicalTrials.gov Archive Site
Change in BMI, blood pressure, waist circumference, waist to hip ratio, lipids, 1,25 dihydroxyvitamin D, and fractional excretion of phosphate [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Change in BMI, blood pressure, waist circumference, waist to hip ratio, lipids, 1,25 dihydroxyvitamin D, and fractional excretion of phosphate [ Time Frame: 12 weeks ]
Not Provided
Not Provided
 
Vitamin D Deficiency, Insulin Resistance and FGF-23
Impact of Vitamin D Deficiency on Insulin Resistance and the Regulation of FGF-23

The purpose of this project is to determine if treating vitamin D deficiency decreases insulin resistance and improves insulin secretion in healthy volunteers. Additionally, this project will investigate if treating vitamin D deficiency affects a new phosphate-regulating hormone called FGF-23.

Vitamin D deficiency or hypovitaminosis D, defined as serum 25 hydroxyvitamin D < or = 20 ng/mL, is prevalent in several populations in the United States, specifically minorities and the elderly. Causes of vitamin D deficiency include lack of exposure to sunlight, malnutrition, and drugs that alter vitamin D metabolism and absorption.

Vitamin D is an essential factor for many organ systems. Data suggest that vitamin D is required for normal insulin secretion by the pancreas. Specifically, animal studies demonstrate that treatment of vitamin D deficiency improves insulin secretion. In humans, there is less consensus about the impact of vitamin D deficiency on insulin resistance. In one study of middle-aged patients with Type 2 diabetes mellitus, no association was seen between serum 25 hydroxyvitamin D levels and a measure of insulin resistance. However, in a larger study of younger glucose tolerant subjects, serum 25 hydroxyvitamin D levels were associated with both insulin secretion and insulin resistance. These data suggest that treatment of vitamin D deficiency may delay or prevent the development of insulin resistance, and thus diabetes mellitus type 2. Repletion of this common vitamin deficiency could therefore have major public health implications for the prevention of diabetes mellitus.

Fibroblast growth factor 23 (FGF-23) is a newly discovered phosphaturic hormone that is regulated by both dietary and serum phosphate. Hormonal regulation of FGF-23, however, is largely unknown. Recent data suggest that vitamin D plays an important role in the regulation of FGF-23. Some groups have shown that inactivation of the vitamin D receptor gene decreases serum FGF-23 levels in mice; administration of 1,25 dihydroxyvitamin D stimulates the transcription of the FGF-23 gene in vitro. Little is known, however, about the regulation of FGF-23 by vitamin D in humans.

Phosphate is critical for bone mineralization, muscle function, signal transduction, and the creation and utilization of energy. Vitamin D deficiency can result in phosphate malabsorption, osteomalacia and increased risk of fractures. Enhanced understanding of the regulation of this new phosphate-regulating hormone, FGF-23, will advance the field of phosphate metabolism.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Vitamin D Deficiency
Drug: Ergocalciferol
Ergocalciferol 50000 international units or matching placebo q week for 12 weeks
  • Experimental: 1
    Ergocalciferol 50000 international units q week for 12 weeks
    Intervention: Drug: Ergocalciferol
  • Placebo Comparator: 2
    Matching placebo q week for 12 weeks
    Intervention: Drug: Ergocalciferol

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
90
February 2008
February 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age 18 to 45 yrs
  • Serum 25-OHD < or = 20 ng/mL
  • At least 1 menses in the last 3 months (females) and normal serum testosterone (males)

Exclusion Criteria:

  • Significant cardiac, hepatic, oncologic, or psychiatric disease
  • History of diabetes mellitus, malabsorption, kidney stones, or recent alcohol excess/abuse (15 drinks per week in the last month)
  • Fasting glucose > 126 mg/dl or 2 hour OGTT > 200 mg/dl
  • 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 metformin or insulin sensitizing agents
  • Serum calcium < 8 or > 11 mg/dL, creatinine > 1.5 mg/dL, or Hgb < 11 gm/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 or testosterone use
  • Urine uhCG positive (females), testosterone < 270 ng/dL (males)
Both
18 Years to 45 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00491322
2006-P-000430/18, 1 K23 DK073356-01
Yes
Sherri-Ann M. Burnett-Bowie, MD, MPH, Massachusetts General Hospital
Massachusetts General Hospital
Not Provided
Principal Investigator: Sherri-Ann M Burnett-Bowie, MD, MPH Massachusetts General Hospital
Massachusetts General Hospital
March 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP