Phase 2
N=70
Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
Chronic Kidney Disease
Bottom Line
View on ClinicalTrials.gov: NCT02552888 ↗Enrolled (actual)
70
Serious AEs
2.9%
Results posted
Apr 2021
Primary outcome: Primary: Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks — 1.1; 0.3 Percentage change
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Immediate release sodium nitrite (Drug); Isoquercetin (Dietary_supplement); placebos (Other)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- Tulane University
- Primary completion
- Jun 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks |
1.1; 0.3 | — |
| SECONDARY Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks |
-16.1; -4.0; -22.2; -10.8; -0.32; 1.06 | — |
| SECONDARY Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 12 Weeks |
0.03; 0.02 | — |
| SECONDARY Mean Change in Endothelial Function Biomarker Endostatin Over 12 Weeks |
-0.02; -0.01 | — |
| SECONDARY Mean Change in Endothelial Function Biomarker Urine Epidermal Growth Factor (UEGF) Over 12 Weeks |
-0.01; 0.23 | — |
| SECONDARY Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks |
0.05; -0.02 | — |
| SECONDARY 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 |
-0.04; -0.04; -0.72; 0.01; -17.1; -30.5 | — |
| SECONDARY Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 12 Weeks |
0.07; -0.17 | — |
| SECONDARY Mean Change in Oxidative Stress Biomarker Low-density Lipoprotein (LDL) Over 12 Weeks |
-1.7; -0.3 | — |
| SECONDARY Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 12 Weeks |
-10.9; 62.2 | — |
Summary
The proposed randomized controlled trial will test the safety and efficacy of combination therapy with sodium nitrite and isoquercetin on endothelial function and inflammation among patients with chronic kidney disease.
Eligibility Criteria
Inclusion Criteria
- Men and women aged 21-74 years old with any race/ethnicity background
- CKD as defined by an eGFR <60 ml/min/1.73 m2 or urinary albumin to creatinine ratio ≥ 30 mg/g or protein to creatinine ratio ≥150 mg/g.
- Systolic BP≥120 and <180 mmHg and/or diastolic BP≥70 and <110 mmHg
Exclusion Criteria
- Allergic to organic nitrite, isoquercetin, niacin, or vitamin C
- Institutionalized (e.g., prisoner, nursing home or skilled nursing facility resident)
- Unable or unwilling to give consent
- Known HIV infection and/or AIDS
- Pregnant or lactating women
- Currently on dialysis
- Previous or current organ or bone marrow transplant
- Receiving immunosuppressive treatment or other immunotherapy
- Receiving chemotherapy or alkylating agents for systemic cancer
- Recent acute myocardial infarction, cerebrovascular accidence or transient ischemic attack, or hospitalization in 3 months
- Acute kidney injury within the previous 3 months
- Currently taking a phosphodiesterase-5 enzyme inhibitor, such as Viagra
- History of chronic headaches
- Chronically receiving fluoroguinolones, cyclosporin (neural, sandimmune), nitrate drug, NSAIDS ( except aspirin ≤ 81 mg daily), allopurinol or uloric, meperidine and related central nervous system (CNS) depressants, oral glucocorticoids, and not willing or able to stop during study period.
- Active infection (i.e. systemic or osteomyelitis)
- Class III or IV heart failure
- History of hemolytic anemia including sickle cell disease
- Hemoglobin <10
- History of chronic obstructive pulmonary disease (COPD)
- Have a positive screen for glucose-6-phosphate dehydrogenase (G6PD) deficiency at screening
- Involvement in other clinical trials
- Current alcohol or other substance abuse
- Current smokers
- Unwillingness to stop flavonoid supplementation
- Unwillingness to stop nitrate and/or nitrite supplementation
Data sourced from ClinicalTrials.gov (NCT02552888). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.