Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks
研究概览
简要总结
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.
详细描述
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. Investigators will recruit 70 albuminuric CKD patients and randomly assign participants to combination therapy with sodium nitrite and isoquercetin or placebo for three months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
treatment
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
干预措施: Immediate release sodium nitrite (Drug)
treatment
Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
干预措施: Isoquercetin (Dietary Supplement)
Placebos
identical placebos.
干预措施: placebos (Other)
结局指标
主要结局
Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks
时间窗: Baseline, 6 weeks, 12 weeks
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.
次要结局
- Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- 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(Baseline, 6 weeks, 12 weeks)
- Mean Change in Oxidative Stress Biomarker Low-density Lipoprotein (LDL) Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- Mean Change in Endothelial Function Biomarker Urine Epidermal Growth Factor (UEGF) Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- Mean Change in Endothelial Function Biomarker Endostatin Over 12 Weeks(Baseline, 6 weeks, 12 weeks)
- Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks(Baseline, 6 weeks, 12 weeks)