Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial

NCT02552888 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: TulaneU1U54GM104940
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease

Keywords

Endothelial Dysfunction; Inflammation; Oxidative Stress; eGFR; Urine Albumin

Outcome Measures

Primary Outcomes (1)

• Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 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.

  Baseline, 6 weeks, 12 weeks

Secondary Outcomes (9)

• 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 Endothelial Function Biomarker Endostatin 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 Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks

  Baseline, 6 weeks, 12 weeks

Other Outcomes (11)

• Mean Percentage Change in Methemoglobin Over 12 Weeks

  Baseline, 6 weeks, 12 weeks

• Mean Change in Isoquercetin Over 12 Weeks

  Baseline, 6 weeks, 12 weeks

• Mean Change in Plasma Nitrite Over 12 Weeks

  Baseline, 6 weeks, 12 weeks

Study Arms (2)

treatment

EXPERIMENTAL

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

Drug: Immediate release sodium nitrite; Dietary Supplement: Isoquercetin

Placebos

PLACEBO COMPARATOR

identical placebos.

Other: placebos

Interventions

Immediate release sodium nitrite DRUG

Immediate release sodium nitrite 40 mg by mouth twice per day

Also known as: TV1001

treatment

Isoquercetin DIETARY_SUPPLEMENT

Isoquercetin 225 mg by mouth once per day

Also known as: 3-O-glucoside

treatment

placebos OTHER

placebos

Placebos

Eligibility Criteria

• Age: 21 Years - 74 Years
• Gender Eligibility Details: participant eligibility is based on self-representation of gender identity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tulane University: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Study Sites (1)

Tulane School of Medicine

New Orleans, Louisiana, 70112, United States

Location

Related Publications (2)

• Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.

  PMID: 37916745 DERIVED

• 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.

  PMID: 33023894 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Inflammation

Interventions

isoquercitrin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr. Jing Chen
• Organization: Tulane School of Medicine

jchen@tulane.edu

5049886110

Study Officials

• Jing Chen, MD

  Tulane University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: September 17, 2015
• Study Start: March 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: April 20, 2021
• Results First Posted: April 20, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: no end date.
• Access Criteria: The de-identified patient level data will be provided directly to the researcher in a secure manner, and the researcher is responsible for protecting the confidentiality and integrity of the data while the research is conducted.

Locations

US (1)