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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Insulin Resistance
Interventions Drug: Vitamin D
Drug: Placebo
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description

Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to 6 months.

.

Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.
Period Title: Overall Study
Started 11 8
Completed 7 7
Not Completed 4 1
Reason Not Completed
Lost to Follow-up             2             0
IV access issues             1             1
Physician Decision             1             0
Arm/Group Title Vitamin D Placebo Total
Hide Arm/Group Description

Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to six months.

.

Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months. Total of all reporting groups
Overall Number of Baseline Participants 11 8 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 11 participants 8 participants 19 participants
42.0  (10.7) 47.3  (11.5) 44.2  (11.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants 8 participants 19 participants
Female
4
  36.4%
2
  25.0%
6
  31.6%
Male
7
  63.6%
6
  75.0%
13
  68.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Non-Hispanic Number Analyzed 11 participants 8 participants 19 participants
2
  18.2%
3
  37.5%
5
  26.3%
Black or African American Number Analyzed 11 participants 8 participants 19 participants
7
  63.6%
5
  62.5%
12
  63.2%
Asian Number Analyzed 11 participants 8 participants 19 participants
0
   0.0%
0
   0.0%
0
   0.0%
Hispanic or Latino Number Analyzed 11 participants 8 participants 19 participants
2
  18.2%
0
   0.0%
2
  10.5%
Other Number Analyzed 11 participants 8 participants 19 participants
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 11 participants 8 participants 19 participants
11 8 19
Hepatic Insulin Sensitivity   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/kg/min
Number Analyzed 11 participants 8 participants 19 participants
1.28  (0.65) 1.10  (0.64) 1.20  (0.63)
[1]
Measure Description: We examine the endogenous glucose production (EGP) to assess hepatic insulin sensitivity at baseline.
Peripheral Glucose Uptake   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/kg/min
Number Analyzed 11 participants 8 participants 19 participants
5.99  (1.18) 6.71  (2.33) 6.29  (1.74)
[1]
Measure Description: We examine the rate of glucose uptake to determine peripheral insulin sensitivity using rate of disappearance (Rd) of glucose.
Evaluated expression of pro-inflammatory gene TNF-α in macrophages   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Ratio of mRNA copy numbers (TNF-α/5HKGs)
Number Analyzed 11 participants 6 participants 17 participants
0.05  (0.03) 0.02  (0.02) 0.04  (0.03)
[1]
Measure Description: 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 polymerase chain reaction (rt-PCR) and will provide a measure of macrophage activation. 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.
[2]
Measure Analysis Population Description: TNFα was measured in 6 participants in placebo group.
Evaluated expression of pro-inflammatory gene IL-6 in macrophages   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Ratio of mRNA copy numbers (IL-6/5HKGs)
Number Analyzed 11 participants 6 participants 17 participants
0.06  (0.05) 0.04  (0.05) 0.05  (0.05)
[1]
Measure Description: 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 polymerase chain reaction (rt-PCR) and will provide a measure of macrophage activation. 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.
[2]
Measure Analysis Population Description: IL-6 was measured in 6 participants in placebo group.
Evaluated expression of pro-inflammatory gene iNOS in macrophages   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Ratio of mRNA copy numbers (iNOS/5HKGs)
Number Analyzed 11 participants 6 participants 17 participants
0.007  (0.008) 0.006  (0.005) 0.007  (0.007)
[1]
Measure Description: 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 polymerase chain reaction (rt-PCR) and will provide a measure of macrophage activation. 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.
[2]
Measure Analysis Population Description: iNOS was measured in 6 participants in placebo group.
Evaluated expression of pro-inflammatory gene PAI-1 in macrophages   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Ratio of mRNA copy numbers (PAI-1/5HKGs)
Number Analyzed 11 participants 6 participants 17 participants
0.03  (0.03) 0.04  (0.03) 0.03  (0.03)
[1]
Measure Description: 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 polymerase chain reaction (rt-PCR) and will provide a measure of macrophage activation. 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.
[2]
Measure Analysis Population Description: PAI-1 was measured in 6 participants in placebo group.
1.Primary Outcome
Title Percent Change in Hepatic Insulin Sensitivity
Hide Description 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.
Time Frame 2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Hepatic insulin sensitivity was measured in 7 (out of 11) participants in the Vitamin D group and in 7 (out of 8) participants in the placebo group at the 3rd study visit due to loss to follow up, withdrawal, or difficulties in obtaining IV access.
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description:
Participants received weekly oral vitamin D drops using a weight-based calculated dosage to reach a target level of ≥30 ng/ml at second visit and a goal level of ≥50 ng/ml at third visit.
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
Overall Number of Participants Analyzed 11 8
Mean (Standard Error)
Unit of Measure: percent change
Percent change between baseline and 2nd visit Number Analyzed 11 participants 8 participants
-19.2  (11.6) 5.8  (22.5)
Percent change between baseline and 3rd visit Number Analyzed 7 participants 7 participants
-33.66  (7.5) 113.7  (65.5)
2.Secondary Outcome
Title Percent Change in Peripheral Glucose Uptake
Hide Description 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.
Time Frame 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Hepatic insulin sensitivity was measured in 7 (out of 11) participants in the Vitamin D group and in 6 (out of 8) participants in the placebo group at the 3rd study visit due to loss to follow up, withdrawal, or difficulties in obtaining IV access.
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description:
Participants received weekly oral vitamin D drops using a weight-based calculated dosage to reach a target level of ≥30 ng/ml at second visit and a goal level of ≥50 ng/ml at third visit.
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
Overall Number of Participants Analyzed 11 8
Mean (Standard Error)
Unit of Measure: percent change
Percent change between baseline and 2nd visit Number Analyzed 11 participants 8 participants
0.48  (8.1) -2.54  (5.8)
Percent change between baseline and 3rd visit Number Analyzed 7 participants 6 participants
-0.98  (7.2) 1.75  (10.1)
3.Secondary Outcome
Title Evaluated Expression of Pro-inflammatory Gene TNF-α
Hide Description 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.
Time Frame 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
TNF-α expression was measured in 7 (out of 11) participants in the Vitamin D group and in 4 (out of 8) participants in the placebo group at the 3rd study visit due to loss to follow up, withdrawal, or difficulties in obtaining IV access. Additionally, 2 participants in placebo group did not provide fat biopsy samples for the study.
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description:
Participants received weekly oral vitamin D drops using a weight-based calculated dosage to reach a target level of ≥30 ng/ml at second visit and a goal level of ≥50 ng/ml at third visit.
Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for three months.
Overall Number of Participants Analyzed 11 6
Mean (Standard Error)
Unit of Measure: Ratio of mRNA copy numbers (TNF-α/5HKGs)
TNF-α (2nd study visit) Number Analyzed 11 participants 6 participants
0.023  (0.006) 0.021  (0.007)
TNF-α (3rd study visit) Number Analyzed 7 participants 4 participants
0.036  (0.009) 0.008  (0.003)
4.Secondary Outcome
Title Evaluated Expression of Pro-inflammatory Gene IL-6
Hide Description 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.
Time Frame 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
IL-6 expression was measured in 7 (out of 11) participants in the Vitamin D group. For the placebo group, 6 of the 8 participants provided fat biopsy samples for the 2nd visit, and 4 participants provided for the 3rd visit due to loss to follow up, withdrawal, or difficulties in obtaining IV access.
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description:

Participants in this group were assigned to receive weekly oral vitamin D drops using a weight-based calculated dosage for three months.

.

Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for three months.
Overall Number of Participants Analyzed 11 6
Mean (Standard Error)
Unit of Measure: Ratio of mRNA copy numbers (IL-6/5HKGs)
IL-6 (2nd study visit) Number Analyzed 11 participants 6 participants
0.019  (0.006) 0.047  (0.018)
IL-6 (3rd study visit) Number Analyzed 7 participants 4 participants
0.022  (0.007) 0.050  (0.029)
5.Secondary Outcome
Title Evaluated Expression of Pro-inflammatory Gene iNOS
Hide Description 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.
Time Frame 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
iNOS expression was measured in 7 (out of 11) participants in the Vitamin D group. For the placebo group, 6 of the 8 participants provided fat biopsy samples for the 2nd visit, and 4 participants provided for the 3rd visit due to loss to follow up, withdrawal, or difficulties in obtaining IV access.
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description:

Participants in this group were assigned to receive weekly oral vitamin D drops using a weight-based calculated dosage for three months.

.

Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for three months.
Overall Number of Participants Analyzed 11 6
Mean (Standard Error)
Unit of Measure: Ratio of mRNA copy numbers (iNOS/5HKGs)
iNOS (2nd study visit) Number Analyzed 11 participants 6 participants
0.004  (0.002) 0.008  (0.005)
iNOS (3rd study visit) Number Analyzed 7 participants 4 participants
0.003  (0.001) 0.005  (0.002)
6.Secondary Outcome
Title Evaluated Expression of Pro-inflammatory Gene PAI-1
Hide Description 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.
Time Frame 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)
Hide Outcome Measure Data
Hide Analysis Population Description
PAI-1 expression was measured in 7 (out of 11) participants in the Vitamin D group. For the placebo group, 6 of the 8 participants provided fat biopsy samples for the 2nd visit, and 4 participants provided for the 3rd visit due to loss to follow up, withdrawal, or difficulties in obtaining IV access.
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description:

Participants in this group were assigned to receive weekly oral vitamin D drops using a weight-based calculated dosage for three months.

.

Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for three months.
Overall Number of Participants Analyzed 11 6
Mean (Standard Error)
Unit of Measure: Ratio of mRNA copy numbers (PAI-1/5HKGs)
PAI-1 (2nd study visit) Number Analyzed 11 participants 6 participants
0.020  (0.008) 0.032  (0.012)
PAI-1 (3rd study visit) Number Analyzed 7 participants 4 participants
0.008  (0.005) 0.019  (0.008)
Time Frame Time enrolled in study (approximately 6 months)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vitamin D Placebo
Hide Arm/Group Description

Participants in this group were assigned to receive weekly oral vitamin D drops using a weight-based calculated dosage for six months.

.

Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for six months.
All-Cause Mortality
Vitamin D Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/11 (0.00%)      0/8 (0.00%)    
Hide Serious Adverse Events
Vitamin D Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/11 (9.09%)      0/8 (0.00%)    
Ear and labyrinth disorders     
benign paroxysmal vertigo *  1/11 (9.09%)  1 0/8 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vitamin D Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/11 (9.09%)      0/8 (0.00%)    
Nervous system disorders     
pre-syncopal episode *  1/11 (9.09%)  1 0/8 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Meredith Hawkins
Organization: Albert Einstein College of Medicine
Phone: 7184302903 ext 2903
EMail: meredith.hawkins@einsteinmed.org
Layout table for additonal information
Responsible Party: Meredith Hawkins, Albert Einstein College of Medicine
ClinicalTrials.gov Identifier: NCT01354964    
Other Study ID Numbers: 2008-225
5K23RR023335-02 ( U.S. NIH Grant/Contract )
First Submitted: May 12, 2011
First Posted: May 17, 2011
Results First Submitted: April 12, 2019
Results First Posted: March 9, 2020
Last Update Posted: November 2, 2020