Comparative Effectiveness of Vitamin D and Repletion Strategies (CEDARS)

This study has been completed.
Sponsor:
Collaborator:
Diabetes Action Research and Education Foundation
Information provided by (Responsible Party):
Bastyr University
ClinicalTrials.gov Identifier:
NCT01524874
First received: November 8, 2011
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

The importance of vitamin D (VitD) in the prevention and treatment of human health conditions has gained increased attention in recent years. As a result, medical providers of all categories are screening clinical VitD status frequently, yet become challenged with how to best advise patients regarding repletion of VitD status, i.e. which form of VitD replacement is most effective. It has been recognized that to achieve significant effects - serum concentrations >30ng/ml (75 nmol/ml) - it is necessary, as well as safe, to recommend substantially higher doses than were previously thought sufficient. These higher doses can be easily achieved orally. This clinical trial aims to compare absorption of three available forms of this fat-soluble vitamin, due to the potential differences in absorption of different preparations. High-quality powdered, chewable and lipid-emulsified VitD are readily available as supplements, yet these have not been systematically compared. This three-arm, randomized clinical trial will compare the difference in serum 25-hydroxycholecalciferol (25-OH)D concentration between the three arms at baseline and after random administration of one of the three VitD preparations for 12-weeks at a dosage of 10,000 IU VitD per day. The investigators hypothesize that the three forms of vitD will result in an equivalent increase in serum 25OHD.


Condition Intervention
Hypovitaminosis D
Insulin Resistance
Diabetes
Dietary Supplement: Vitamin D3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: A Comparative Effectiveness Trial of High-quality Vitamin D3 Nutritional Supplements to Replete Serum Vitamin D

Resource links provided by NLM:


Further study details as provided by Bastyr University:

Primary Outcome Measures:
  • Change in mean serum 25-hydroxycholecalciferol concentration [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    To compare the change in serum 25-hydroxycholecalciferol (25-OHD) concentration between three forms of supplemental vitamin D3: a lipid-emulsified form administered in a sesame oil base, a non-emulsified chewable tablet, and a non-emulsified form administered as a capsule, following 12 weeks of supplementation (10,000 IU/day) in D3 insufficient patients (baseline 25-OHD <33ng/ml (82.5 nmol/ml)) patients.


Secondary Outcome Measures:
  • Proportion of participants reaching 25-hydroxycholecalciferol concentration >=33ng/ml (82.5 nmol/ml) between groups [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    To compare the proportion of participants reaching a laboratory "normal" 25-hydroxycholecalciferol concentration >=33ng/ml (82.5 nmol/ml) between D3 supplement groups following 12-weeks of D3 supplementation at 10,000 IU.day

  • Change in mean Klotho protein concentration [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    To explore the expression of Klotho protein, and analytes associated with VitD homeostasis, comparing VitD sufficient, i.e. 25-OHD >=33ng/ml (82.5 nmol/ml), patients to those who are VitD insufficient, i.e. 25-OHD <33ng/ml, at baseline screenings, and to compare Klotho protein expression in VitD insufficient participants before and after D3 supplementation (10,000 IU/day), stratified by supplement group assignment.

  • Change in Toll-like receptor concentration in monocytes [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    To explore the change in IFN-gamma induced TLR-4 expression in human monocytes (ex-vivo), comparing VitD sufficient, i.e. 25-OHD >=33ng/ml (82.5 nmol/ml), patients to those who are VitD insufficient, i.e. 25-OHD <33ng/ml, at baseline screenings, and to compare the change in IFN-gamma induced TLR-4 expression in human monocytes (ex-vivo) between VitD groups, following 12 weeks of supplementation with one of three forms of VitD3: lipid-emulsified, non-emulsified chewable tablet, and a non-emulsified encapsulated form.

  • Change in mean cardiometabolic risk factors [ Time Frame: Baseline- 12 weeks ] [ Designated as safety issue: No ]
    To explore change in mean fasting glucose, hemoglobin A1c, total cholesterol, fasting insulin, HOMA-IR, LDL, HDL-C, and triglycerides will be reported following 12-weeks of D3 supplementation (10,000 IU/day) in healthy humans


Enrollment: 66
Study Start Date: August 2010
Study Completion Date: November 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Powder D3 Capsule - 2,000 IU per Cap
Vital Nutrients
Dietary Supplement: Vitamin D3
10,000 IU per Day for 12 Weeks
Other Name: Calcitriol
Active Comparator: Chewable D3 Tablet - 2,000 IU per Tab
Integrative Therapeutics Inc.
Dietary Supplement: Vitamin D3
10,000 IU per Day for 12 Weeks
Other Name: Calcitriol
Active Comparator: Liquid D3 Drop - 2,000 IU per Drop
Biotics Research
Dietary Supplement: Vitamin D3
10,000 IU per Day for 12 Weeks
Other Name: Calcitriol

Detailed Description:

VitD has numerous hormonal effects, including regulation of Ca2+ and Mg2+, as well as effects on numerous genes, including insulin and androgens. Mounting literature demonstrates associations between VitD insufficiency and cancer, diabetes and heart disease. VitD insufficiency, defined by concentration of serum 25-hydroxycholecalciferol (25-OHD) <33ng/ml (82.5 nmol/ml), is common at all latitudes; the prevalence is estimated at ~35% in "healthy" populations. VitD testing and replacement is gaining popularity in clinical practice. It is not known whether there is a difference in the effect of equivalent doses of emulsified vs. non-emulsified cholecalciferol (VitD3) supplementation, reflected by quantitative changes in serum 25-OHD. However, clinical observations revealed that in an average of 4.4 months, subjects taking 4000 iu daily of the emulsified form of cholecalciferol improved their 25-OHD levels by 6.76 ng/mL more than those taking 5,000 iu daily of the non-emulsified form. The safety of taking 10,000 IU/day has been confirmed. Taking this dose for 12 weeks should cause a robust increase in serum 25-OHD. This study will provide preliminary data comparing three high quality VitD3 supplements, one a powdered capsule, one a chewable tablet, and the other a lipid-emulsified liquid. Future studies will compare the "better" supplement to conventional VitD replacement using VitD2.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Provision of informed consent
  • Between18-65 years of age; there is an age-related decline in the absorption, transport or liver hydroxylation of orally-consumed VitD (Harris, 1999) therefore adults older than 65 will be excluded. This population is also at greater risk of being on medications with potential medication interactions, e.g. anticoagulants.
  • Willingness to perform baseline screening tests: serum 25-OHD, CBC, Comprehensive metabolic chemistry panel (electrolytes, hepatic and renal function tests, lipids, HgA1C, insulin and glucose)
  • Screening serum 25-OHD <33ng/ml (82.5 nmol/ml). If >=33ng/ml (82.5 nmol/ml), subjects will participate in the research study as baseline controls for the nested studies of Klotho and TLR-4.
  • Ability to read and speak English
  • Willingness to be randomized to one of three active treatments for 3 months

Exclusion Criteria:

  • Subjects who have a serum baseline 25-OHD >=33ng/ml (82.5 nmol/ml) will be excluded once the VitD sufficient baseline control recruitment goal is met
  • Subjects who have historical or current use of extra-dietary VitD, other than what is in a multivitamin, for the previous 3 months.
  • LFTs: AST>60 U/L; ALT>65 U/L; Alkaline phosphatase >120 U/L. Total bilirubin>1.5 mg/dL
  • Serum creatinine>1.4 mg/dL; BUN >25 mg/dL5. Subjects who are pregnant, or could become pregnant, unless they are using regular birth control (OCPs, condoms, IUD).
  • Subjects who have established osteoporosis.
  • Subjects who have history or symptoms of a parathyroid disorder.
  • Subjects who have difficulty swallowing pills.
  • Subjects who are unwilling to use sunscreen.
  • Subjects who have had a past adverse reaction to sunscreen.
  • Subjects who are taking medications over the previous 3 months that interfere with the metabolism of VitD (anti-convulsants, anti-coagulants, oral corticosteroids, or barbiturates).
  • Subjects with any psychological conditions or substance abuse that may make the subject non- adherent, such as history of bipolar disorder, mania, untreated anxiety or other mood disorder, as determined by the site PI.
  • Other severe illness or mental incapacity that, in the opinion of the site PI, would render the potential subject incapable of participating in the study.
  • Allergy to sesame oil base
  • Heart arrhythmia
  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: NCT01524874

Locations
United States, Hawaii
Lokahi Health Center
Kailua Kona, Hawaii, United States, 96740
United States, Washington
Bastyr University
Kenmore, Washington, United States, 98028
Sponsors and Collaborators
Bastyr University
Diabetes Action Research and Education Foundation
Investigators
Principal Investigator: Ryan Bradley, ND, MPH Bastyr University
  More Information

No publications provided

Responsible Party: Bastyr University
ClinicalTrials.gov Identifier: NCT01524874     History of Changes
Other Study ID Numbers: H30-B11
Study First Received: November 8, 2011
Last Updated: January 31, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Bastyr University:
vitamin d
cholecalciferol
nutritional supplements
hypovitaminosis d
klotho
toll like receptor 4

Additional relevant MeSH terms:
Insulin Resistance
Rickets
Avitaminosis
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Calcium Metabolism Disorders
Vitamin D Deficiency
Deficiency Diseases
Malnutrition
Nutrition Disorders
Calcitriol
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Calcium Channel Agonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014