search
Back to results

Comparative Effectiveness of Vitamin D and Repletion Strategies (CEDARS)

Primary Purpose

Hypovitaminosis D, Insulin Resistance, Diabetes

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vitamin D3
Vitamin D3
Vitamin D3
Sponsored by
Bastyr University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypovitaminosis D focused on measuring vitamin d, cholecalciferol, nutritional supplements, hypovitaminosis d, klotho, toll like receptor 4

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Lokahi Health Center
  • Bastyr University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Powder D3 Capsule - 2,000 IU per Cap

Chewable D3 Tablet - 2,000 IU per Tab

Liquid D3 Drop - 2,000 IU per Drop

Arm Description

Vital Nutrients

Integrative Therapeutics Inc.

Biotics Research

Outcomes

Primary Outcome Measures

Change in mean serum 25-hydroxycholecalciferol concentration
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
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
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
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
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

Full Information

First Posted
November 8, 2011
Last Updated
January 31, 2012
Sponsor
Bastyr University
Collaborators
Diabetes Action Research and Education Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT01524874
Brief Title
Comparative Effectiveness of Vitamin D and Repletion Strategies
Acronym
CEDARS
Official Title
A Comparative Effectiveness Trial of High-quality Vitamin D3 Nutritional Supplements to Replete Serum Vitamin D
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bastyr University
Collaborators
Diabetes Action Research and Education Foundation

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypovitaminosis D, Insulin Resistance, Diabetes
Keywords
vitamin d, cholecalciferol, nutritional supplements, hypovitaminosis d, klotho, toll like receptor 4

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Powder D3 Capsule - 2,000 IU per Cap
Arm Type
Active Comparator
Arm Description
Vital Nutrients
Arm Title
Chewable D3 Tablet - 2,000 IU per Tab
Arm Type
Active Comparator
Arm Description
Integrative Therapeutics Inc.
Arm Title
Liquid D3 Drop - 2,000 IU per Drop
Arm Type
Active Comparator
Arm Description
Biotics Research
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Calcitriol
Intervention Description
10,000 IU per Day for 12 Weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Calcitriol
Intervention Description
10,000 IU per Day for 12 Weeks
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D3
Other Intervention Name(s)
Calcitriol
Intervention Description
10,000 IU per Day for 12 Weeks
Primary Outcome Measure Information:
Title
Change in mean serum 25-hydroxycholecalciferol concentration
Description
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.
Time Frame
Baseline and 12 weeks
Secondary Outcome Measure Information:
Title
Proportion of participants reaching 25-hydroxycholecalciferol concentration >=33ng/ml (82.5 nmol/ml) between groups
Description
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
Time Frame
12 weeks
Title
Change in mean Klotho protein concentration
Description
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.
Time Frame
Baseline and 12 weeks
Title
Change in Toll-like receptor concentration in monocytes
Description
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.
Time Frame
Baseline and 12 weeks
Title
Change in mean cardiometabolic risk factors
Description
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
Time Frame
Baseline- 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Bradley, ND, MPH
Organizational Affiliation
Bastyr University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lokahi Health Center
City
Kailua Kona
State/Province
Hawaii
ZIP/Postal Code
96740
Country
United States
Facility Name
Bastyr University
City
Kenmore
State/Province
Washington
ZIP/Postal Code
98028
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Comparative Effectiveness of Vitamin D and Repletion Strategies

We'll reach out to this number within 24 hrs