Improving the Understanding of the Response to Vitamin D Supplementation

It is the investigators hypothesis that the current method of evaluating vitamin D status, measuring circulating 25-hydroxy vitamin D is not providing the full metabolic picture, and is therefore inadequate. The investigators liken this concept to the evolution of cholesterol where initially, total cholesterol was the only measurement, and have since determined the importance of HDL, LDL and triglycerides in evaluating patient status. Similarly, the investigators feel measurement of other vitamin D components such as sulfated vitamin D, circulating vitamin D3 and 3-epi 25-hydroxy vitamin D will offer more comprehensive information about a patient's vitamin D status.

It is our overarching hypothesis that a "vitamin D assay panel," will enhance understanding of vitamin D status. It is our expectation that the enhanced understanding based on improved measurement capability will ultimately translate to improved definition of vitamin D status and need for supplementation on an individual level.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency
• Intervention / Treatment: Dietary supplement: cholecalciferol; Dietary supplement: Placebo

Detailed Description

This hypothesis is supported by several observations. First, recent work finds previously unappreciated vitamin D metabolites, notably 3 epi-25(OH)D348 and sulfated 25(OH)D3, in virtually all human sera and circulating in amounts that vary widely between individuals. These compounds may be measured by current "25(OH)D" assays,46, 63 and thereby confound accuracy of such measurements. Secondly, substantial but inadequately understood variability of 25(OH)D response to supplementation and UV exposure exists.15, 42-44 It is likely that currently unappreciated genetic and/or physiologic factors, e.g., differences in absorption or degradation, underpin these observations. Our panel will allow definition of these differences. Finally, the inadequacy of our current approach to classify vitamin D status (singular 25(OH)D measurement) is exemplified by the great between-individual variability in the PTH/25(OH)D relationship as noted above.8, 64 Thus, the investigators believe that exploration of a "vitamin D assay panel," consisting of measurements that reflect input (cholecalciferol and ergocalciferol) and confounders to the 25(OH)D assay [3 epi-25(OH)D and sulfated 25(OH)D] is essential to accurately define optimal vitamin D status and to determine the ideal approach for vitamin D repletion.

To begin testing this hypothesis, the Specific Aims of this research are to document the vitamin D profile response defined as change in serum concentration of:

1. 25(OH)D
2. cholecalciferol
3. 3 epi-25(OH)D
4. Sulfated 25(OH)D following four months of supplementation with 2,200 IU of daily vitamin D3 in postmenopausal women. Our primary outcome variable is the effect of supplementation on serum 25(OH)D3; secondary outcomes are change in cholecalciferol, 3 epi-25(OH)D3 and sulfated 25(OH)D3.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy, community-dwelling ambulatory postmenopausal White, non-Hispanic women
• Able and willing to sign informed consent
• Baseline serum 25(OH)D concentration of 10-29 ng/mL
• Willing to not alter the amount of their baseline vitamin D supplementation during the course of this study
• Willing to use sunscreen (SPF ≥15) when sun exposure of > 15 minutes is expected

Exclusion Criteria:

• Presence of any measurable circulating 25(OH)D2 on screening measurement
• Current hypercalcemia (serum calcium > 10.5 mg/dl) or untreated primary hyperparathyroidism
• History of nephrolithiasis
• Known risk factors for hypercalcemia, e.g., malignancy, tuberculosis, sarcoidosis
• History of any form of cancer within the past five years with the exception of adequately treated squamous cell or basal cell skin carcinoma
• Renal failure; defined as a calculated creatinine clearance (using the Cockroft-Gault approach) of ≤ 35 ml/minute
• Severe end-organ disease, e.g., cardiovascular, hepatic, hematologic, pulmonary, etc., which might limit the ability to complete this study
• Known metabolic bone disease, e.g., Paget's disease, osteomalacia
• Treatment with any drug known to interfere with vitamin D metabolism, e.g., phenytoin, phenobarbital
• Treatment with high dose vitamin D (≥ 50,000 IU weekly) or any active metabolites of vitamin D, e.g., calcitriol, within six months of screening
• Use of tanning beds or salons or unwillingness to utilize sunscreen during periods of sun exposure of 15 minutes or longer
• Planned trips/vacations likely to be associated with substantial amounts of sun exposure during the course of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2000 IU vitamin D3; Cholecalciferol 2,000 IU capsules	Dietary supplement: cholecalciferol; 2000 IU cholecalciferol gelcaps by mouth daily
Placebo Comparator: Placebo; Non-matching placebo, gelatin filled capsules	Dietary supplement: Placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum 25-hydroxy Vitamin D3	Our primary outcome variable is the effect of supplementation on change in serum 25(OH)D3;	Baseline, 1 and 4 months post supplementation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Parameters of the Vitamin D Assay Panel	Secondary outcomes are change in cholecalciferol, 24,25(OH)D3 and free 25(OH)D3.	Baseline, 1 and 4 months post supplementation

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: October 27, 2011
• First Submitted That Met QC Criteria: November 1, 2011
• First Posted (Estimate): November 4, 2011

Study Record Updates

• Last Update Posted (Estimate): November 25, 2016
• Last Update Submitted That Met QC Criteria: October 4, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: hypovitaminosis D; vitamin D insufficiency; low vitamin D
• Additional Relevant MeSH Terms: Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vitamin D Deficiency; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 2011-0601