Improving the Understanding of the Response to Vitamin D Supplementation

Phase 3

Completed

Conditions: Vitamin D Deficiency

Interventions: Dietary Supplement: Placebo
Dietary Supplement: cholecalciferol

Registration Number: NCT01465178

Lead Sponsor: University of Wisconsin, Madison

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 62

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Non-matching placebo, gelatin filled capsules
2000 IU vitamin D3	cholecalciferol	Cholecalciferol 2,000 IU capsules

Primary Outcome Measures

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

Secondary Outcome Measures

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