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Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation

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ClinicalTrials.gov Identifier: NCT01354964
Recruitment Status : Completed
First Posted : May 17, 2011
Results First Posted : March 9, 2020
Last Update Posted : November 2, 2020
Sponsor:
Collaborator:
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Meredith Hawkins, Albert Einstein College of Medicine

Tracking Information
First Submitted Date  ICMJE May 12, 2011
First Posted Date  ICMJE May 17, 2011
Results First Submitted Date  ICMJE April 12, 2019
Results First Posted Date  ICMJE March 9, 2020
Last Update Posted Date November 2, 2020
Actual Study Start Date  ICMJE March 13, 2009
Actual Primary Completion Date June 3, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 24, 2020)
Percent Change in Hepatic Insulin Sensitivity [ Time Frame: 2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months) ]
Endogenous glucose production (EGP) was assessed at each study visit to evaluate hepatic insulin sensitivity. Percent change between the EGP at baseline and second visit (after treatment for up to 3 months with Vitamin D to reach a target level of ≥30 ng/ml), and baseline and third visits (after treatment for up to 6 months with Vitamin D in order to reach a target level of ≥50 ng/ml) will be calculated.
Original Primary Outcome Measures  ICMJE
 (submitted: May 16, 2011)
Hepatic insulin sensitivity [ Time Frame: 2 and 4 months ]
We will examine endogenous glucose production to assess hepatic insulin sensitivity.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2020)
  • Percent Change in Peripheral Glucose Uptake [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
    The rate of glucose uptake to determine peripheral insulin sensitivity was measured using the rate of disappearance (Rd) of glucose at each study visit. Percent change between the Rd at baseline and second visit (after treatment with Vitamin D for up to 3 months to target level of ≥30 ng/ml), and baseline and third visits (after treatment with Vitamin D for up to 6 months to target level of ≥50 ng/ml) will be calculated.
  • Evaluated Expression of Pro-inflammatory Gene TNF-α [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
    Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. TNF-α gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
  • Evaluated Expression of Pro-inflammatory Gene IL-6 [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
    Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. IL-6 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
  • Evaluated Expression of Pro-inflammatory Gene iNOS [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
    Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. iNOS gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
  • Evaluated Expression of Pro-inflammatory Gene PAI-1 [ Time Frame: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months) ]
    Adipose tissue macrophages will be isolated from subcutaneous abdominal adipose tissue, and will be quantified by fluorescence activated cell sorting (FACS) analysis. PAI-1 gene expression will be examined by real-time (rt-PCR) and will provide a measure of macrophage activation at baseline, at 2nd study visit (after treatment with Vitamin D to a goal level of ≥30 ng/ml), and at 3rd study visit (goal Vitamin D level of ≥50 ng/ml). The mRNA copy number is then compared with a reference gene copy number (5 commonly used house keeping genes [HKGs]) as a ratio, which is a measure of relative gene expression.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2011)
  • Peripheral insulin sensitivity [ Time Frame: 2 and 4 months ]
    We will examine the rate of glucose uptake to determine peripheral inslin sensitivity.
  • Adipose tissue inflammatory markers/Cytokines in plasma [ Time Frame: 2 and 4 months ]
    Inflammatory markers-PAI-1, IL-6, TNF-a, iNOS
  • Neuropsychological Testing [ Time Frame: 4 months ]
    We will conduct neuropsychological testing to assess cognitive function.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation
Official Title  ICMJE Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation
Brief Summary The purpose of this research is to study the effects of Vitamin D supplementation on the body's response to insulin (a hormone that controls blood sugar), on inflammation, and on specific cells and processes in fat tissue.
Detailed Description

Over the last several years, studies have shown that low vitamin D levels may increase risk of developing Type 2 Diabetes. The investigators will administer vitamin D3 (cholecalciferol) to non-diabetic, insulin resistant subjects with vitamin D deficiency (total vitamin D levels <20 ng/ml) to increase the level of vitamin D3. The investigators will study the effects of increased Vitamin D on insulin action, adipose tissue inflammation, and on certain cells and processes in fat tissue.

Investigators will study participants with a procedure called a "pancreatic clamp" study. During the clamp procedure, glucose (a sugar) and insulin (a hormone produced in the pancreas that regulates the amount of glucose in the blood) are infused with an intravenous catheter, and blood samples are collected periodically throughout the procedure to measure blood sugar levels and the levels of several hormones that are found in the body and are related to glucose metabolism. Adipose tissue inflammation will be measured using the following inflammatory markers: IL-6, PAI-1, TNF-alpha, and iNOS.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Insulin Resistance
Intervention  ICMJE
  • Drug: Vitamin D
    Other Name: Vitamin D3 (cholecalciferol)
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Vitamin D
    Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to six months.
    Intervention: Drug: Vitamin D
  • Placebo Comparator: Placebo
    Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 24, 2020)
19
Original Estimated Enrollment  ICMJE
 (submitted: May 16, 2011)
25
Actual Study Completion Date  ICMJE September 3, 2015
Actual Primary Completion Date June 3, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Serum 25(OH)D<20ng/ml
  • Insulin Resistant based on HOMA-IR score of >3
  • Able and willing to provide informed consent
  • BMI 20-35

Exclusion Criteria:

  • HIV/AIDS
  • History of any cancer
  • Sarcoidosis
  • Alcohol or substance abuse
  • Cushing's syndrome
  • Primary hyperparathyroidism
  • Nephrolithiasis
  • Pregnancy or breastfeeding
  • Regular visits to a tanning salon
  • Hypercalcemia or hypocalcemia
  • Untreated or uncontrolled hypertension
  • Any chronic illness requiring medication, other than arthritis, hypertension and hyperlipidemia
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01354964
Other Study ID Numbers  ICMJE 2008-225
5K23RR023335-02 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Meredith Hawkins, Albert Einstein College of Medicine
Study Sponsor  ICMJE Albert Einstein College of Medicine
Collaborators  ICMJE National Center for Research Resources (NCRR)
Investigators  ICMJE
Principal Investigator: Meredith A Hawkins, M.D., M.S. Albert Einstein College of Medicine
PRS Account Albert Einstein College of Medicine
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP