Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial

Tulane University

Status and phase: Completed; Phase 2

Conditions: Chronic Kidney Disease

Treatments: Drug: Immediate release sodium nitrite; Other: placebos; Dietary Supplement: Isoquercetin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02552888

1U54GM104940 (U.S. NIH Grant/Contract)

TulaneU

Details and patient eligibility

About

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.

Full 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.

Enrollment: 70 patients

Sex: All

Ages: 21 to 74 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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70 participants in 2 patient groups, including a placebo group

treatment

Experimental group

Description:

Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.

Treatment:

Dietary Supplement: Isoquercetin

Drug: Immediate release sodium nitrite

Placebos

Placebo Comparator group

Description:

identical placebos.

Treatment:

Other: placebos