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Improving the Understanding of the Response to Vitamin D Supplementation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01465178
Recruitment Status : Completed
First Posted : November 4, 2011
Results First Posted : November 25, 2016
Last Update Posted : November 25, 2016
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Vitamin D Deficiency Dietary Supplement: cholecalciferol Dietary Supplement: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Diagnostic
Official Title: Improving the Understanding of the Response to Vitamin D Supplementation
Study Start Date : December 2011
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. Change in Serum 25-hydroxy Vitamin D3 [ Time Frame: 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 :
  1. Change in Parameters of the Vitamin D Assay Panel [ Time Frame: Baseline, 1 and 4 months post supplementation ]
    Secondary outcomes are change in cholecalciferol, 24,25(OH)D3 and free 25(OH)D3.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01465178

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United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
Merck Sharp & Dohme Corp.
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Principal Investigator: Neil Binkley, M.D. University of Wisconsin, Madison
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Responsible Party: University of Wisconsin, Madison Identifier: NCT01465178    
Other Study ID Numbers: 2011-0601
First Posted: November 4, 2011    Key Record Dates
Results First Posted: November 25, 2016
Last Update Posted: November 25, 2016
Last Verified: October 2016
Keywords provided by University of Wisconsin, Madison:
hypovitaminosis D
vitamin D insufficiency
low vitamin D
Additional relevant MeSH terms:
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Vitamin D Deficiency
Deficiency Diseases
Nutrition Disorders
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Growth Substances
Bone Density Conservation Agents