Improving the Understanding of the Response to Vitamin D Supplementation

Vitamin D Deficiency Clinical Trial

Official title:

Improving the Understanding of the Response to Vitamin D Supplementation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01465178
• Other study ID #: 2011-0601
• Status: Completed
• Phase: Phase 3
• First received: October 27, 2011
• Last updated: June 16, 2015
• Start date: December 2011
• Est. completion date: December 2014

Study information

• Verified date: June 2015
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 50 Years and older

Eligibility

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 12-20 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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Vitamin D Deficiency

Intervention

Dietary Supplement:
• cholecalciferol
2000 IU cholecalciferol gelcaps by mouth daily
• Placebo
matching placebo

Locations

Country	Name	City	State
United States	University of Wisconsin	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Change in parameters of the vitamin D assay panel	Secondary outcomes are change in cholecalciferol, 3 epi-25(OH)D3 and sulfated 25(OH)D3.	Baseline, 1 and 2 months post supplementation	No