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
  Purpose

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.


Condition Intervention
Vitamin D Deficiency
Drug: Ergocalciferol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Impact of Vitamin D Deficiency on Insulin Resistance and the Regulation of FGF-23

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in insulin resistance, insulin secretion, and FGF-23 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 90
Study Start Date: May 2006
Study Completion Date: February 2008
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Ergocalciferol 50000 international units q week for 12 weeks
Drug: Ergocalciferol
Ergocalciferol 50000 international units or matching placebo q week for 12 weeks
Placebo Comparator: 2
Matching placebo q week for 12 weeks
Drug: Ergocalciferol
Ergocalciferol 50000 international units or matching placebo q week for 12 weeks

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00491322

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Sherri-Ann M Burnett-Bowie, MD, MPH Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Sherri-Ann M. Burnett-Bowie, MD, MPH, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00491322     History of Changes
Other Study ID Numbers: 2006-P-000430/18, 1 K23 DK073356-01
Study First Received: June 22, 2007
Last Updated: March 26, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Vitamin D
Vitamin D deficiency
Insulin resistance
Diabetes
Diabetes mellitus
FGF-23
FGF23
Phosphate

Additional relevant MeSH terms:
Insulin Resistance
Vitamin D Deficiency
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Ergocalciferols
Vitamin D
Vitamins
Insulin
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances
Hypoglycemic Agents

ClinicalTrials.gov processed this record on July 22, 2014