Trial Outcomes & Findings for Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial (NCT NCT02552888)
NCT ID: NCT02552888
Last Updated: 2021-04-20
Results Overview
FMD was measured using high resolution ultrasound on the brachial artery. FMD was calculated as the maximal percentage change in vessel size during hyperemia . The mean changes between baseline, 6 weeks and 12 weeks in FMD with 95% CI were calculated using linear mixed effects model.
COMPLETED
PHASE2
70 participants
Baseline, 6 weeks, 12 weeks
2021-04-20
Participant Flow
Participant milestones
| Measure |
Placebos
identical placebos.
placebos: placebos
|
Treatment
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
35
|
|
Overall Study
COMPLETED
|
34
|
34
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Placebos
identical placebos.
placebos: placebos
|
Treatment
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
|---|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
Baseline characteristics by cohort
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
19 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
38 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
16 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
|
Age, Continuous
|
61.3 years
STANDARD_DEVIATION 10.4 • n=99 Participants
|
62.2 years
STANDARD_DEVIATION 10.2 • n=107 Participants
|
61.8 years
STANDARD_DEVIATION 10.3 • n=206 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
26 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=99 Participants
|
22 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=99 Participants
|
20 Participants
n=107 Participants
|
36 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=99 Participants
|
35 participants
n=107 Participants
|
70 participants
n=206 Participants
|
|
Baseline Metabolic Panel of Study Participants by Treatment Allocation
Fasting plasma glucose, mean, mg/dL
|
119 mg/dL
STANDARD_DEVIATION 44 • n=99 Participants
|
124 mg/dL
STANDARD_DEVIATION 70 • n=107 Participants
|
121.5 mg/dL
STANDARD_DEVIATION 57 • n=206 Participants
|
|
Baseline Metabolic Panel of Study Participants by Treatment Allocation
Total cholesterol, mean, mg/dL
|
178 mg/dL
STANDARD_DEVIATION 43 • n=99 Participants
|
171 mg/dL
STANDARD_DEVIATION 50 • n=107 Participants
|
174.5 mg/dL
STANDARD_DEVIATION 46.5 • n=206 Participants
|
|
Baseline Metabolic Panel of Study Participants by Treatment Allocation
HDL-cholesterol, mean, mg/dL
|
48 mg/dL
STANDARD_DEVIATION 13 • n=99 Participants
|
47 mg/dL
STANDARD_DEVIATION 14 • n=107 Participants
|
47.5 mg/dL
STANDARD_DEVIATION 13.5 • n=206 Participants
|
|
Baseline Metabolic Panel of Study Participants by Treatment Allocation
LDL-cholesterol, mean, mg/dL
|
107 mg/dL
STANDARD_DEVIATION 34 • n=99 Participants
|
100 mg/dL
STANDARD_DEVIATION 37 • n=107 Participants
|
103.5 mg/dL
STANDARD_DEVIATION 35.5 • n=206 Participants
|
|
Baseline Blood Pressure of Study Participants by Treatment Allocation
Systolic blood pressure, mean, mmHg
|
129 mmHg
STANDARD_DEVIATION 15 • n=99 Participants
|
129 mmHg
STANDARD_DEVIATION 15 • n=107 Participants
|
129 mmHg
STANDARD_DEVIATION 15 • n=206 Participants
|
|
Baseline Blood Pressure of Study Participants by Treatment Allocation
Diastolic blood pressure, mean, mmHg
|
73 mmHg
STANDARD_DEVIATION 7 • n=99 Participants
|
75 mmHg
STANDARD_DEVIATION 11 • n=107 Participants
|
74 mmHg
STANDARD_DEVIATION 9 • n=206 Participants
|
|
Baseline Body Mass Index of Study Participants by Treatment Allocation
|
30.9 kg/m^2
STANDARD_DEVIATION 5.6 • n=99 Participants
|
32.5 kg/m^2
STANDARD_DEVIATION 5.7 • n=107 Participants
|
31.7 kg/m^2
STANDARD_DEVIATION 5.65 • n=206 Participants
|
|
Baseline Estimated Glomerular Filtration Rate of Study Participants by Treatment Allocation
|
51 ml/min/1.73m^2
STANDARD_DEVIATION 22 • n=99 Participants
|
45 ml/min/1.73m^2
STANDARD_DEVIATION 16 • n=107 Participants
|
48 ml/min/1.73m^2
STANDARD_DEVIATION 19 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
FMD was measured using high resolution ultrasound on the brachial artery. FMD was calculated as the maximal percentage change in vessel size during hyperemia . The mean changes between baseline, 6 weeks and 12 weeks in FMD with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks
|
1.1 Percentage change
Interval -0.1 to 2.3
|
0.3 Percentage change
Interval -0.9 to 1.5
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of Vascular Adhesion Molecule-1(VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), E-selectin, and von Willebrand Factor (vWF). The mean changes between baseline, 6 weeks and 12 weeks in VCAM-1, ICAM-1, E-selectin and vWF with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
ICAM, ng/mL
|
-16.1 ng/mL
Interval -41.5 to 9.3
|
-4.0 ng/mL
Interval -29.0 to 21.0
|
|
Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
VCAM-1, ng/mL
|
-22.2 ng/mL
Interval -49.3 to 5.0
|
-10.8 ng/mL
Interval -37.5 to 15.9
|
|
Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
E-Selecint, ng/mL
|
-0.32 ng/mL
Interval -3.14 to 2.5
|
1.06 ng/mL
Interval -1.73 to 3.84
|
|
Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
vWF, ng/mL
|
-683 ng/mL
Interval -3784.0 to 2419.0
|
2744 ng/mL
Interval -328.0 to 5815.0
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of Asymmetrical DiMethylArginine (ADMA). The mean changes between baseline, 6 weeks and 12 weeks in ADMA with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 12 Weeks
|
0.03 umol/mL
Interval -0.02 to 0.08
|
0.02 umol/mL
Interval -0.03 to 0.07
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of endostatin. The mean changes between baseline, 6 weeks and 12 weeks in endostatin with 95% CI were calculated using linear mixed effects model, and the log transformed endostatin was calculated.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Endothelial Function Biomarker Endostatin Over 12 Weeks
|
-0.02 log (ng/mL)
Interval -0.08 to 0.05
|
-0.01 log (ng/mL)
Interval -0.08 to 0.05
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A urine sample was taken for each participant to measure the levels of Urine Epidermal Growth Factor (UEGF). The mean changes between baseline, 6 weeks and 12 weeks in UEGF with 95% CI were calculated using linear mixed effects model, and the log transformed Urine EGF/creatinine ratio was calculated.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Endothelial Function Biomarker Urine Epidermal Growth Factor (UEGF) Over 12 Weeks
|
-0.01 log (pg/g)
Interval -0.39 to 0.37
|
0.23 log (pg/g)
Interval -0.14 to 0.61
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of C-Reactive Protein (CRP). The mean changes between baseline, 6 weeks and 12 weeks in CRP with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks
|
0.05 mg/mL
Interval -0.31 to 0.42
|
-0.02 mg/mL
Interval -0.38 to 0.33
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of Tumor Necrosis Factor-α (TNF-a), interleukin-17 (IL-17), interleukin-1β (IL-1beta), and Monocyte Chemoattractant Protein-1 (MCP-1). The mean changes between baseline, 6 weeks and 12 weeks in TNF-a, IL-17, IL-1beta, MCP-1 with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Inflammatory Biomarkers Tumor Necrosis Factor-α (TNF-a), Interleukin-17 (IL-17), Interleukin-1β (IL-1beta), and Monocyte Chemoattractant Protein-1 (MCP-1) Over 12 Weeks
TNF-a, pg/mL
|
-0.04 pg/mL
Interval -0.2 to 0.12
|
-0.04 pg/mL
Interval -0.2 to 0.12
|
|
Mean Change in Inflammatory Biomarkers Tumor Necrosis Factor-α (TNF-a), Interleukin-17 (IL-17), Interleukin-1β (IL-1beta), and Monocyte Chemoattractant Protein-1 (MCP-1) Over 12 Weeks
IL-17, pg/mL
|
-0.72 pg/mL
Interval -1.8 to 0.36
|
0.01 pg/mL
Interval -1.05 to 1.08
|
|
Mean Change in Inflammatory Biomarkers Tumor Necrosis Factor-α (TNF-a), Interleukin-17 (IL-17), Interleukin-1β (IL-1beta), and Monocyte Chemoattractant Protein-1 (MCP-1) Over 12 Weeks
IL-1 beta, pg/mL
|
-17.1 pg/mL
Interval -77.5 to 43.4
|
-30.5 pg/mL
Interval -90.0 to 29.0
|
|
Mean Change in Inflammatory Biomarkers Tumor Necrosis Factor-α (TNF-a), Interleukin-17 (IL-17), Interleukin-1β (IL-1beta), and Monocyte Chemoattractant Protein-1 (MCP-1) Over 12 Weeks
MCP-1, pg/mL
|
-6.0 pg/mL
Interval -25.0 to 13.0
|
0.6 pg/mL
Interval -18.0 to 19.3
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of interleukin-6 (IL-6). The mean changes between baseline, 6 weeks and 12 weeks in interleukin-6 (IL-6) with 95% CI were calculated using linear mixed effects model, and the log transformed IL-6 was calculated.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 12 Weeks
|
0.07 log (pg/mL)
Interval -0.06 to 0.2
|
-0.17 log (pg/mL)
Interval -0.3 to -0.04
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of low-density lipoprotein (LDL). The mean changes between baseline, 6 weeks and 12 weeks in LDL with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Oxidative Stress Biomarker Low-density Lipoprotein (LDL) Over 12 Weeks
|
-1.7 ng/mL
Interval -3.9 to 0.5
|
-0.3 ng/mL
Interval -2.4 to 1.9
|
SECONDARY outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of nitrotyrosine. The mean changes between baseline, 6 weeks and 12 weeks in nitrotyrosine with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 12 Weeks
|
-10.9 pg/mL
Interval -96.9 to 75.2
|
62.2 pg/mL
Interval -22.6 to 147.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of methemoglobin. The mean percentage change between baseline, 6 weeks and 12 weeks in methemoglobin with 95% CI was calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Percentage Change in Methemoglobin Over 12 Weeks
|
-0.06 Percentage change
Interval -0.11 to -0.01
|
-0.05 Percentage change
Interval -0.11 to -0.01
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of isoquercetin. The mean changes between baseline, 6 weeks and 12 weeks in isoquercetin with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Isoquercetin Over 12 Weeks
|
166 ug/L
Interval 102.0 to 230.0
|
11.7 ug/L
Interval -51.1 to 74.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of plasma nitrite. The mean changes between baseline, 6 weeks and 12 weeks in plasma nitrite with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Plasma Nitrite Over 12 Weeks
|
-0.07 micromol/L
Interval -0.2 to 0.05
|
-0.11 micromol/L
Interval -0.23 to 0.01
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
Estimated-Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The equation is GFR = 141 \* min(Scr/κ,1)α \* max(Scr/κ, 1)-1.209 \* 0.993Age \* 1.018 \[if female\] \* 1.159 \[if black\]. Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. The mean changes between baseline, 6 weeks and 12 weeks in eGFR with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Estimated-Glomerular Filtration Rate (eGFR) Over 12 Weeks
|
0.1 mL/min/1.73 m^2
Interval -2.3 to 2.5
|
0.2 mL/min/1.73 m^2
Interval -2.2 to 2.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline,12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of total cholesterol, Low Density Lipoprotein (LDL)-cholesterol and High Density Lipoprotein (HDL)-cholesterol. The mean changes between baseline and 12 weeks in total cholesterol, Low Density Lipoprotein (LDL)-cholesterol and High Density Lipoprotein (HDL)-cholesterol with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Lipid Profile Biomarkers Total Cholesterol, Low Density Lipoprotein (LDL)-Cholesterol and High Density Lipoprotein (HDL)-Cholesterol Over 12 Weeks
Total Cholesterol, mg/dL
|
-1.6 mg/dL
Interval -10.5 to 7.2
|
3.9 mg/dL
Interval -4.9 to 12.8
|
|
Mean Change in Lipid Profile Biomarkers Total Cholesterol, Low Density Lipoprotein (LDL)-Cholesterol and High Density Lipoprotein (HDL)-Cholesterol Over 12 Weeks
LDL-cholesterol, mg/dL
|
-1.9 mg/dL
Interval -7.4 to 3.7
|
0.9 mg/dL
Interval -7.4 to 3.7
|
|
Mean Change in Lipid Profile Biomarkers Total Cholesterol, Low Density Lipoprotein (LDL)-Cholesterol and High Density Lipoprotein (HDL)-Cholesterol Over 12 Weeks
HDL-cholesterol, mg/dL
|
0.9 mg/dL
Interval -1.7 to 3.4
|
2.2 mg/dL
Interval -0.4 to 4.7
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline,12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of triglycerides. The mean changes between baseline and 12 weeks in triglycerides with 95% CI were calculated using linear mixed effects model, and the log transformed triglyceride was calculated.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Lipid Profile Biomarker Triglycerides Over 12 Weeks
|
-0.09 log (mg/dL)
Interval -0.4 to 4.7
|
-0.01 log (mg/dL)
Interval -0.14 to 0.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of hemoglobin. The mean changes between baseline, 6 weeks and 12 weeks in hemoglobin with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Hemoglobin Over 12 Weeks
|
-0.25 g/dL
Interval -0.46 to -0.04
|
-0.13 g/dL
Interval -0.34 to 0.07
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A blood sample was drawn for each participant to measure the levels of plasma nitrate. The mean changes between baseline, 6 weeks and 12 weeks in plasma nitrate with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Plasma Nitrate Over 12 Weeks
|
15.4 umol/L
Interval 5.9 to 25.0
|
-6.3 umol/L
Interval -15.7 to 3.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
A urine sample was taken for each participant to measure the levels of urinary albumin-to-creatinine ratios. The mean changes between baseline, 6 weeks and 12 weeks in urinary albumin-to-creatinine ratios with 95% CI were calculated using linear mixed effects model, and the log transformed urinary albumin-to-creatinine ratios was calculated.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Urinary Albumin-to-creatinine Ratios Over 12 Weeks
|
0.04 log (mg/g)
Interval -0.27 to 0.36
|
0.02 log (mg/g)
Interval -0.29 to 0.33
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
Blood pressure was measured using the OMRON HEM-907 XL BP Monitor per standard protocol by trained and certified research staff. The mean changes between baseline, 6 weeks and 12 weeks in blood pressure with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Blood Pressure Over 12 Weeks
Systolic blood pressure, mmHg
|
-2.2 mm Hg
Interval -6.8 to 2.4
|
-0.7 mm Hg
Interval -5.3 to 3.8
|
|
Mean Change in Blood Pressure Over 12 Weeks
Diastolic blood pressure, mmHg
|
-2.5 mm Hg
Interval -5.0 to -0.1
|
0.1 mm Hg
Interval -2.3 to 2.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 6 weeks, 12 weeksPopulation: Mean Changes Over 12 Weeks (95% CI)
Pulse was measured at the brachial artery per standard protocol by trained and certified research staff. The mean changes between baseline, 6 weeks and 12 weeks in pulse with 95% CI were calculated using linear mixed effects model.
Outcome measures
| Measure |
Treatment
n=35 Participants
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 Participants
identical placebos.
placebos: placebos
|
|---|---|---|
|
Mean Change in Pulse Over 12 Weeks
|
0.6 beat/minute
Interval -1.7 to 2.3
|
-0.5 beat/minute
Interval -2.8 to 1.9
|
Adverse Events
Treatment
Placebos
Serious adverse events
| Measure |
Treatment
n=35 participants at risk
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 participants at risk
identical placebos.
placebos: placebos
|
|---|---|---|
|
Cardiac disorders
Serious Adverse Event - Inpatient hospitalization
|
2.9%
1/35 • Number of events 1 • Each participant was assessed for adverse events in the duration of 3 months.
|
2.9%
1/35 • Number of events 1 • Each participant was assessed for adverse events in the duration of 3 months.
|
Other adverse events
| Measure |
Treatment
n=35 participants at risk
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Immediate release sodium nitrite: Immediate release sodium nitrite 40 mg by mouth twice per day
Isoquercetin: Isoquercetin 225 mg by mouth once per day
|
Placebos
n=35 participants at risk
identical placebos.
placebos: placebos
|
|---|---|---|
|
Cardiac disorders
Adverse Events
|
31.4%
11/35 • Number of events 55 • Each participant was assessed for adverse events in the duration of 3 months.
|
40.0%
14/35 • Number of events 63 • Each participant was assessed for adverse events in the duration of 3 months.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place