Vitamin D Deficiency, Insulin Resistance and FGF-23

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00491322
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 92
• Location: 1
• Arms: 2
• Duration (Months): 21.1
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Vitamin D Deficiency	Dietary Supplement: Ergocalciferol; Dietary Supplement: Ergocalciferol placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Impact of Vitamin D Deficiency on Insulin Resistance and the Regulation of FGF-23
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ergocalciferol group Ergocalciferol 50000 international units once a week for 12 weeks	Dietary Supplement: Ergocalciferol; Ergocalciferol 50000 international units once a week for 12 weeks
Placebo Comparator: Ergocalciferol Placebo group Matching placebo once a week for 12 weeks	Dietary Supplement: Ergocalciferol placebo; Ergocalciferol placebo once a week for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Fibroblast Growth Factor 23 (FGF23) After 12 Weeks of Weekly Ergocalciferol 50000 Units [12 weeks]

   Fibroblast growth factor 23 (FGF23) is a phosphate and vitamin D regulating hormone.

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 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

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Sherri-Ann M Burnett-Bowie, MD, MPH, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Sherri-Ann M. Burnett-Bowie, Assistant Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00491322
• Other Study ID Numbers: 2006-P-000430/18; K23DK073356
• First Posted: Jun 26, 2007
• Last Update Posted: May 2, 2018
• Last Verified: Apr 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sherri-Ann M. Burnett-Bowie, Assistant Professor of Medicine, 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; Ergocalciferols; Vitamin D

Study Results

Participant Flow

Recruitment Details	Subjects were enrolled from 2006-2008. Subjects were healthy volunteers recruited from the community

Arm/Group Title	Ergocalciferol Group	Placebo Group
Arm/Group Description	Ergocalciferol 50000 international units once a week for 12 weeks	Matching placebo once a week for 12 weeks
Period Title: Overall Study
STARTED	41	51
COMPLETED	40	50
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Ergocalciferol Group	Placebo Group	Total
Arm/Group Description	Ergocalciferol 50000 international units once a week for 12 weeks	Matching placebo once a week for 12 weeks	Total of all reporting groups
Overall Participants	40	50	90
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	40 100%	50 100%	90 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	28 (7)	29 (9)	28 (8)
Sex: Female, Male (Count of Participants)
Female	24 60%	31 62%	55 61.1%
Male	16 40%	19 38%	35 38.9%
Region of Enrollment (participants) [Number]
United States	40 100%	50 100%	90 100%

Outcome Measures

1. Primary Outcome

Title	Fibroblast Growth Factor 23 (FGF23) After 12 Weeks of Weekly Ergocalciferol 50000 Units
Description	Fibroblast growth factor 23 (FGF23) is a phosphate and vitamin D regulating hormone.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ergocalciferol Group	Ergocalciferol Placebo Group
Arm/Group Description	Participants receiving ergocalciferol 50000 units weekly for 12 weeks	Participants receiving matching ergocalciferol placebo weekly for 12 weeks
Measure Participants	40	50
Mean (Standard Deviation) [pg/mL]	74 (42)	39 (29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ergocalciferol Group
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments
	Method	ANOVA
	Comments

Adverse Events

Time Frame	12 to 38 weeks
Adverse Event Reporting Description	Subjects were monitored during the12 weeks of the intervention at their baseline, week 4, week 8, and week 12 visits for adverse events. Subjects were counseled to contact us after study completion if they had any concerns. During the 26 weeks after study completion, no subject contact the investigative team with an adverse event or concern.
Arm/Group Title	Ergocalciferol Group		Placebo Group
Arm/Group Description	Ergocalciferol 50,000 international units once a week for 12 weeks		Matching placebo once a week for 12 weeks
All Cause Mortality
	Ergocalciferol Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ergocalciferol Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/50 (0%)
Other (Not Including Serious) Adverse Events
	Ergocalciferol Group		Placebo Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		1/50 (2%)
Endocrine disorders
Asymptomatic hypocalcemia	0/40 (0%)		1/50 (2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.