Improving the Understanding of the Response to Vitamin D Supplementation

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Wisconsin, Madison
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01465178
First received: October 27, 2011
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Vitamin D Deficiency
Dietary Supplement: cholecalciferol
Dietary Supplement: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Diagnostic
Official Title: Improving the Understanding of the Response to Vitamin D Supplementation

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Change in serum 25-hydroxy vitamin D3 [ Time Frame: Baseline, 1 and 4 months post supplementation ] [ Designated as safety issue: No ]
    Our primary outcome variable is the effect of supplementation on change in serum 25(OH)D3;


Secondary Outcome Measures:
  • Change in parameters of the vitamin D assay panel [ Time Frame: Baseline, 1 and 2 months post supplementation ] [ Designated as safety issue: No ]
    Secondary outcomes are change in cholecalciferol, 3 epi-25(OH)D3 and sulfated 25(OH)D3.


Estimated Enrollment: 62
Study Start Date: December 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 2000 IU vitamin D3 Dietary Supplement: cholecalciferol
2000 IU cholecalciferol gelcaps by mouth daily
Placebo Comparator: Matching Placebo Dietary Supplement: Placebo
matching 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.
  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01465178

Contacts
Contact: Diane Krueger, BS 608-265-6410 dckruege@wisc.edu
Contact: Jessie Libber, BS 608-265-6410 libber@wisc.edu

Locations
United States, Wisconsin
University of Wisconsin Recruiting
Madison, Wisconsin, United States, 53705
Contact: Diane Krueger, BS    608-265-6410    dckruege@wisc.edu   
Contact: Jessie Libber, BS    608-265-6410    libber@wisc.edu   
Principal Investigator: Neil Binkley, MD         
Sponsors and Collaborators
University of Wisconsin, Madison
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01465178     History of Changes
Other Study ID Numbers: 2011-0601
Study First Received: October 27, 2011
Last Updated: March 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
hypovitaminosis D
vitamin D insufficiency
low vitamin D

Additional relevant MeSH terms:
Vitamin D Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Cholecalciferol
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014