Trial Outcomes & Findings for Effect of Vitamin D Repletion on Insulin Resistance and Systemic Inflammation (NCT NCT01354964)
NCT ID: NCT01354964
Last Updated: 2020-11-02
Results Overview
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.
COMPLETED
PHASE2
19 participants
2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months)
2020-11-02
Participant Flow
Participant milestones
| Measure |
Vitamin D
Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to 6 months.
.
|
Placebo
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
8
|
|
Overall Study
COMPLETED
|
7
|
7
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
Vitamin D
Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to 6 months.
.
|
Placebo
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
0
|
|
Overall Study
IV access issues
|
1
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
TNFα was measured in 6 participants in placebo group.
Baseline characteristics by cohort
| Measure |
Vitamin D
n=11 Participants
Participants received weekly oral vitamin D drops using a weight-based calculated dosage for up to six months.
.
|
Placebo
n=8 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D) for up to six months.
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.0 years
STANDARD_DEVIATION 10.7 • n=11 Participants
|
47.3 years
STANDARD_DEVIATION 11.5 • n=8 Participants
|
44.2 years
STANDARD_DEVIATION 11.1 • n=19 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=11 Participants
|
2 Participants
n=8 Participants
|
6 Participants
n=19 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=11 Participants
|
6 Participants
n=8 Participants
|
13 Participants
n=19 Participants
|
|
Race/Ethnicity, Customized
White Non-Hispanic
|
2 Participants
n=11 Participants
|
3 Participants
n=8 Participants
|
5 Participants
n=19 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=11 Participants
|
5 Participants
n=8 Participants
|
12 Participants
n=19 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=11 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=19 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
2 Participants
n=11 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=19 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=11 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=19 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=11 Participants
|
8 participants
n=8 Participants
|
19 participants
n=19 Participants
|
|
Hepatic Insulin Sensitivity
|
1.28 mg/kg/min
STANDARD_DEVIATION 0.65 • n=11 Participants
|
1.10 mg/kg/min
STANDARD_DEVIATION 0.64 • n=8 Participants
|
1.20 mg/kg/min
STANDARD_DEVIATION 0.63 • n=19 Participants
|
|
Peripheral Glucose Uptake
|
5.99 mg/kg/min
STANDARD_DEVIATION 1.18 • n=11 Participants
|
6.71 mg/kg/min
STANDARD_DEVIATION 2.33 • n=8 Participants
|
6.29 mg/kg/min
STANDARD_DEVIATION 1.74 • n=19 Participants
|
|
Evaluated expression of pro-inflammatory gene TNF-α in macrophages
|
0.05 Ratio of mRNA copy numbers (TNF-α/5HKGs)
STANDARD_DEVIATION 0.03 • n=11 Participants • TNFα was measured in 6 participants in placebo group.
|
0.02 Ratio of mRNA copy numbers (TNF-α/5HKGs)
STANDARD_DEVIATION 0.02 • n=6 Participants • TNFα was measured in 6 participants in placebo group.
|
0.04 Ratio of mRNA copy numbers (TNF-α/5HKGs)
STANDARD_DEVIATION 0.03 • n=17 Participants • TNFα was measured in 6 participants in placebo group.
|
|
Evaluated expression of pro-inflammatory gene IL-6 in macrophages
|
0.06 Ratio of mRNA copy numbers (IL-6/5HKGs)
STANDARD_DEVIATION 0.05 • n=11 Participants • IL-6 was measured in 6 participants in placebo group.
|
0.04 Ratio of mRNA copy numbers (IL-6/5HKGs)
STANDARD_DEVIATION 0.05 • n=6 Participants • IL-6 was measured in 6 participants in placebo group.
|
0.05 Ratio of mRNA copy numbers (IL-6/5HKGs)
STANDARD_DEVIATION 0.05 • n=17 Participants • IL-6 was measured in 6 participants in placebo group.
|
|
Evaluated expression of pro-inflammatory gene iNOS in macrophages
|
0.007 Ratio of mRNA copy numbers (iNOS/5HKGs)
STANDARD_DEVIATION 0.008 • n=11 Participants • iNOS was measured in 6 participants in placebo group.
|
0.006 Ratio of mRNA copy numbers (iNOS/5HKGs)
STANDARD_DEVIATION 0.005 • n=6 Participants • iNOS was measured in 6 participants in placebo group.
|
0.007 Ratio of mRNA copy numbers (iNOS/5HKGs)
STANDARD_DEVIATION 0.007 • n=17 Participants • iNOS was measured in 6 participants in placebo group.
|
|
Evaluated expression of pro-inflammatory gene PAI-1 in macrophages
|
0.03 Ratio of mRNA copy numbers (PAI-1/5HKGs)
STANDARD_DEVIATION 0.03 • n=11 Participants • PAI-1 was measured in 6 participants in placebo group.
|
0.04 Ratio of mRNA copy numbers (PAI-1/5HKGs)
STANDARD_DEVIATION 0.03 • n=6 Participants • PAI-1 was measured in 6 participants in placebo group.
|
0.03 Ratio of mRNA copy numbers (PAI-1/5HKGs)
STANDARD_DEVIATION 0.03 • n=17 Participants • PAI-1 was measured in 6 participants in placebo group.
|
PRIMARY outcome
Timeframe: 2nd clamp visit (after up to 3 months) and 3rd clamp visit (after up to 6 months)Population: 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.
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.
Outcome measures
| Measure |
Vitamin D
n=11 Participants
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.
|
Placebo
n=8 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
|
|---|---|---|
|
Percent Change in Hepatic Insulin Sensitivity
Percent change between baseline and 2nd visit
|
-19.2 percent change
Standard Error 11.6
|
5.8 percent change
Standard Error 22.5
|
|
Percent Change in Hepatic Insulin Sensitivity
Percent change between baseline and 3rd visit
|
-33.66 percent change
Standard Error 7.5
|
113.7 percent change
Standard Error 65.5
|
SECONDARY outcome
Timeframe: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)Population: 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.
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.
Outcome measures
| Measure |
Vitamin D
n=11 Participants
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.
|
Placebo
n=8 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
|
|---|---|---|
|
Percent Change in Peripheral Glucose Uptake
Percent change between baseline and 2nd visit
|
0.48 percent change
Standard Error 8.1
|
-2.54 percent change
Standard Error 5.8
|
|
Percent Change in Peripheral Glucose Uptake
Percent change between baseline and 3rd visit
|
-0.98 percent change
Standard Error 7.2
|
1.75 percent change
Standard Error 10.1
|
SECONDARY outcome
Timeframe: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)Population: 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.
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.
Outcome measures
| Measure |
Vitamin D
n=11 Participants
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.
|
Placebo
n=6 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
|
|---|---|---|
|
Evaluated Expression of Pro-inflammatory Gene TNF-α
TNF-α (2nd study visit)
|
0.023 Ratio of mRNA copy numbers (TNF-α/5HKGs)
Standard Error 0.006
|
0.021 Ratio of mRNA copy numbers (TNF-α/5HKGs)
Standard Error 0.007
|
|
Evaluated Expression of Pro-inflammatory Gene TNF-α
TNF-α (3rd study visit)
|
0.036 Ratio of mRNA copy numbers (TNF-α/5HKGs)
Standard Error 0.009
|
0.008 Ratio of mRNA copy numbers (TNF-α/5HKGs)
Standard Error 0.003
|
SECONDARY outcome
Timeframe: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)Population: 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.
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.
Outcome measures
| Measure |
Vitamin D
n=11 Participants
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.
|
Placebo
n=6 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
|
|---|---|---|
|
Evaluated Expression of Pro-inflammatory Gene IL-6
IL-6 (2nd study visit)
|
0.019 Ratio of mRNA copy numbers (IL-6/5HKGs)
Standard Error 0.006
|
0.047 Ratio of mRNA copy numbers (IL-6/5HKGs)
Standard Error 0.018
|
|
Evaluated Expression of Pro-inflammatory Gene IL-6
IL-6 (3rd study visit)
|
0.022 Ratio of mRNA copy numbers (IL-6/5HKGs)
Standard Error 0.007
|
0.050 Ratio of mRNA copy numbers (IL-6/5HKGs)
Standard Error 0.029
|
SECONDARY outcome
Timeframe: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)Population: 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.
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.
Outcome measures
| Measure |
Vitamin D
n=11 Participants
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.
|
Placebo
n=6 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
|
|---|---|---|
|
Evaluated Expression of Pro-inflammatory Gene iNOS
iNOS (2nd study visit)
|
0.004 Ratio of mRNA copy numbers (iNOS/5HKGs)
Standard Error 0.002
|
0.008 Ratio of mRNA copy numbers (iNOS/5HKGs)
Standard Error 0.005
|
|
Evaluated Expression of Pro-inflammatory Gene iNOS
iNOS (3rd study visit)
|
0.003 Ratio of mRNA copy numbers (iNOS/5HKGs)
Standard Error 0.001
|
0.005 Ratio of mRNA copy numbers (iNOS/5HKGs)
Standard Error 0.002
|
SECONDARY outcome
Timeframe: 2nd clamp visit (up to 3 months) and 3rd clamp visit (up to 6 months)Population: 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.
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.
Outcome measures
| Measure |
Vitamin D
n=11 Participants
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.
|
Placebo
n=6 Participants
Participants received weekly oral placebo drops (similar in taste and appearance to vitamin D).
|
|---|---|---|
|
Evaluated Expression of Pro-inflammatory Gene PAI-1
PAI-1 (2nd study visit)
|
0.020 Ratio of mRNA copy numbers (PAI-1/5HKGs)
Standard Error 0.008
|
0.032 Ratio of mRNA copy numbers (PAI-1/5HKGs)
Standard Error 0.012
|
|
Evaluated Expression of Pro-inflammatory Gene PAI-1
PAI-1 (3rd study visit)
|
0.008 Ratio of mRNA copy numbers (PAI-1/5HKGs)
Standard Error 0.005
|
0.019 Ratio of mRNA copy numbers (PAI-1/5HKGs)
Standard Error 0.008
|
Adverse Events
Vitamin D
Placebo
Serious adverse events
| Measure |
Vitamin D
n=11 participants at risk
Participants in this group were assigned to receive weekly oral vitamin D drops using a weight-based calculated dosage for six months.
.
|
Placebo
n=8 participants at risk
Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for six months.
|
|---|---|---|
|
Ear and labyrinth disorders
benign paroxysmal vertigo
|
9.1%
1/11 • Number of events 1 • Time enrolled in study (approximately 6 months)
|
0.00%
0/8 • Time enrolled in study (approximately 6 months)
|
Other adverse events
| Measure |
Vitamin D
n=11 participants at risk
Participants in this group were assigned to receive weekly oral vitamin D drops using a weight-based calculated dosage for six months.
.
|
Placebo
n=8 participants at risk
Participants in this group were assigned to receive weekly oral placebo drops (similar in taste and appearance to vitamin D) for six months.
|
|---|---|---|
|
Nervous system disorders
pre-syncopal episode
|
9.1%
1/11 • Number of events 1 • Time enrolled in study (approximately 6 months)
|
0.00%
0/8 • Time enrolled in study (approximately 6 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place