Clinical trial NCT02552888: Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
Official title: Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Keywords: Endothelial Dysfunction
Inflammation
Oxidative Stress
eGFR
Urine Albumin
Lead sponsor: Tulane University
Sponsor class: OTHER
Collaborators: name: National Institute of General Medical Sciences (NIGMS)
First posted: 2015-09-17
Enrollment: 70
Sex: ALL
Minimum age (years): 21
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
Secondary outcomes:
measure: Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Endothelial Function Biomarker Endostatin Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Endothelial Function Biomarker Urine Epidermal Growth Factor (UEGF) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: 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
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Oxidative Stress Biomarker Low-density Lipoprotein (LDL) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
Other outcomes:
measure: Mean Percentage Change in Methemoglobin Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Isoquercetin Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Plasma Nitrite Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Estimated-Glomerular Filtration Rate (eGFR) Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Lipid Profile Biomarkers Total Cholesterol, Low Density Lipoprotein (LDL)-Cholesterol and High Density Lipoprotein (HDL)-Cholesterol Over 12 Weeks
timeFrame: Baseline,12 weeks
measure: Mean Change in Lipid Profile Biomarker Triglycerides Over 12 Weeks
timeFrame: Baseline,12 weeks
measure: Mean Change in Hemoglobin Over 12 Weeks
timeFrame: baseline, 6 weeks, 12 weeks
measure: Mean Change in Plasma Nitrate Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Urinary Albumin-to-creatinine Ratios Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Blood Pressure Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Mean Change in Pulse Over 12 Weeks
timeFrame: Baseline, 6 weeks, 12 weeks
Locations:
city: New Orleans
country: United States
facility: Tulane School of Medicine
state: Louisiana
Study officials:
affiliation: Tulane University
name: Jing Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen J, Hamm LL, Bundy JD, Kumbala DR, Bodana S, Chandra S, Chen CS, Starcke CC, Guo Y, Schaefer CM, Lustigova E, Mahone E, Vadalia AM, Livingston T, Obst K, Hernandez J, Bokhari SR, Kleinpeter M, Alper AB, Lukitsch I, He H, Nieman DC, He J. Combination Treatment with Sodium Nitrite and Isoquercetin on Endothelial Dysfunction among Patients with CKD: A Randomized Phase 2 Pilot Trial. Clin J Am Soc Nephrol. 2020 Nov 6;15(11):1566-1575. doi: 10.2215/CJN.02020220. Epub 2020 Oct 6.