Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial (NICE)

March 23, 2021 updated by: Tulane University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 74 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: treatment
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
Immediate release sodium nitrite 40 mg by mouth twice per day
Other Names:
  • TV1001
Dietary supplement: Isoquercetin
Isoquercetin 225 mg by mouth once per day
Other Names:
  • 3-O-glucoside
Placebo Comparator: Placebos
identical placebos.
Other: placebos
placebos

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks
Time Frame: 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.
Baseline, 6 weeks, 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of Vascular Adhesion Molecule-1(VCAM-1), Intercellular Adhesion Molecule-1 (ICAM-1), E-selectin, and von Willebrand Factor (vWF). The mean changes between baseline, 6 weeks and 12 weeks in VCAM-1, ICAM-1, E-selectin and vWF with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of Asymmetrical DiMethylArginine (ADMA). The mean changes between baseline, 6 weeks and 12 weeks in ADMA with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Endostatin Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of endostatin. The mean changes between baseline, 6 weeks and 12 weeks in endostatin with 95% CI were calculated using linear mixed effects model, and the log transformed endostatin was calculated.
Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Urine Epidermal Growth Factor (UEGF) Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A urine sample was taken for each participant to measure the levels of Urine Epidermal Growth Factor (UEGF). The mean changes between baseline, 6 weeks and 12 weeks in UEGF with 95% CI were calculated using linear mixed effects model, and the log transformed Urine EGF/creatinine ratio was calculated.
Baseline, 6 weeks, 12 weeks
Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of C-Reactive Protein (CRP). The mean changes between baseline, 6 weeks and 12 weeks in CRP with 95% CI were calculated using linear mixed effects model.
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
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of Tumor Necrosis Factor-α (TNF-a), interleukin-17 (IL-17), interleukin-1β (IL-1beta), and Monocyte Chemoattractant Protein-1 (MCP-1). The mean changes between baseline, 6 weeks and 12 weeks in TNF-a, IL-17, IL-1beta, MCP-1 with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of interleukin-6 (IL-6). The mean changes between baseline, 6 weeks and 12 weeks in interleukin-6 (IL-6) with 95% CI were calculated using linear mixed effects model, and the log transformed IL-6 was calculated.
Baseline, 6 weeks, 12 weeks
Mean Change in Oxidative Stress Biomarker Low-density Lipoprotein (LDL) Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of low-density lipoprotein (LDL). The mean changes between baseline, 6 weeks and 12 weeks in LDL with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of nitrotyrosine. The mean changes between baseline, 6 weeks and 12 weeks in nitrotyrosine with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mean Percentage Change in Methemoglobin Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of methemoglobin. The mean percentage change between baseline, 6 weeks and 12 weeks in methemoglobin with 95% CI was calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Isoquercetin Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of isoquercetin. The mean changes between baseline, 6 weeks and 12 weeks in isoquercetin with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Plasma Nitrite Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of plasma nitrite. The mean changes between baseline, 6 weeks and 12 weeks in plasma nitrite with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Estimated-Glomerular Filtration Rate (eGFR) Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
Estimated-Glomerular Filtration Rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. The equation is GFR = 141 * min(Scr/κ,1)α * max(Scr/κ, 1)-1.209 * 0.993Age * 1.018 [if female] * 1.159 [if black]. Scr is serum creatinine (mg/dL), κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. The mean changes between baseline, 6 weeks and 12 weeks in eGFR with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Lipid Profile Biomarkers Total Cholesterol, Low Density Lipoprotein (LDL)-Cholesterol and High Density Lipoprotein (HDL)-Cholesterol Over 12 Weeks
Time Frame: Baseline,12 weeks
A blood sample was drawn for each participant to measure the levels of total cholesterol, Low Density Lipoprotein (LDL)-cholesterol and High Density Lipoprotein (HDL)-cholesterol. The mean changes between baseline and 12 weeks in total cholesterol, Low Density Lipoprotein (LDL)-cholesterol and High Density Lipoprotein (HDL)-cholesterol with 95% CI were calculated using linear mixed effects model.
Baseline,12 weeks
Mean Change in Lipid Profile Biomarker Triglycerides Over 12 Weeks
Time Frame: Baseline,12 weeks
A blood sample was drawn for each participant to measure the levels of triglycerides. The mean changes between baseline and 12 weeks in triglycerides with 95% CI were calculated using linear mixed effects model, and the log transformed triglyceride was calculated.
Baseline,12 weeks
Mean Change in Hemoglobin Over 12 Weeks
Time Frame: baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of hemoglobin. The mean changes between baseline, 6 weeks and 12 weeks in hemoglobin with 95% CI were calculated using linear mixed effects model.
baseline, 6 weeks, 12 weeks
Mean Change in Plasma Nitrate Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A blood sample was drawn for each participant to measure the levels of plasma nitrate. The mean changes between baseline, 6 weeks and 12 weeks in plasma nitrate with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Urinary Albumin-to-creatinine Ratios Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
A urine sample was taken for each participant to measure the levels of urinary albumin-to-creatinine ratios. The mean changes between baseline, 6 weeks and 12 weeks in urinary albumin-to-creatinine ratios with 95% CI were calculated using linear mixed effects model, and the log transformed urinary albumin-to-creatinine ratios was calculated.
Baseline, 6 weeks, 12 weeks
Mean Change in Blood Pressure Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
Blood pressure was measured using the OMRON HEM-907 XL BP Monitor per standard protocol by trained and certified research staff. The mean changes between baseline, 6 weeks and 12 weeks in blood pressure with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks
Mean Change in Pulse Over 12 Weeks
Time Frame: Baseline, 6 weeks, 12 weeks
Pulse was measured at the brachial artery per standard protocol by trained and certified research staff. The mean changes between baseline, 6 weeks and 12 weeks in pulse with 95% CI were calculated using linear mixed effects model.
Baseline, 6 weeks, 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Tulane University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of General Medical Sciences (NIGMS)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jing Chen, MD, Tulane University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 10, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 17, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 20, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TulaneU
  • 1U54GM104940 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

deidentified data sets may be available to other researchers.

IPD Sharing Time Frame

no end date.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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