Improving the Understanding of the Response to Vitamin D Supplementation

NCT ID: NCT01465178

Last Updated: 2016-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2014-12-31

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.

Conditions

Vitamin D Deficiency

Keywords

hypovitaminosis D; vitamin D insufficiency; low vitamin D

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: DOUBLE

Study Groups

2000 IU vitamin D3

Cholecalciferol 2,000 IU capsules

Group Type: ACTIVE_COMPARATOR

cholecalciferol

Intervention Type: DIETARY_SUPPLEMENT

2000 IU cholecalciferol gelcaps by mouth daily

Placebo

Non-matching placebo, gelatin filled capsules

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

matching placebo

Interventions

cholecalciferol

2000 IU cholecalciferol gelcaps by mouth daily

Intervention Type: DIETARY_SUPPLEMENT

Placebo

matching placebo

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Neil Binkley, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Other Identifiers

2011-0601

Identifier Type: -

Identifier Source: org_study_id