Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Immediate release sodium nitrite; Isoquercetin; placebos
Intervention description: Immediate release sodium nitrite 40 mg by mouth twice per day; Isoquercetin 225 mg by mouth once per day; placebos
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 70.0
Sex: All
Minimum age: 21 Years
Maximum age: 74 Years
Healthy volunteers: No
Keywords: Endothelial Dysfunction; Inflammation; Oxidative Stress; eGFR; Urine Albumin

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