Chronic Kidney DiseasePhase 2NICENCT02552888

Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial

A Phase 2 study testing Immediate release sodium nitrite and Isoquercetin in people with Chronic Kidney Disease, run by Tulane University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 21 to 74 years
Conditions the study is for: Chronic Kidney Disease
What is being tested?: Immediate release sodium nitrite and Isoquercetin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 70 participants
Where: 1 siteUnited States
Study dates: Mar 2016to Jun 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 21 to 74 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 25Show fewer

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 locations and contacts

1 site in 1 country.

United States1 site

Tulane School of Medicine
New Orleans, Louisiana, 70112

Other trials in United States

About this study

Read the 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.

Conditions: Chronic Kidney Disease
Being tested: Immediate release sodium nitrite, Isoquercetin, placebos
Keywords: Endothelial Dysfunction, Inflammation, Oxidative Stress, eGFR, Urine Albumin
Medical subject headings: Renal Insufficiency, Chronic, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Immediate release sodium nitriteDrug
Also called TV1001
Immediate release sodium nitrite 40 mg by mouth twice per day
IsoquercetinDietary supplement
Also called 3-O-glucoside
Isoquercetin 225 mg by mouth once per day
placebosOther
placebos

Study groups in NCT02552888
Study group	Role	What they receive
treatment	Experimental	Immediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day. Receives: Drug: Immediate release sodium nitrite; Dietary Supplement: Isoquercetin
Placebos	Placebo comparator	identical placebos. Receives: Other: placebos

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Endostatin Over 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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Urine Epidermal Growth Factor (UEGF) Over 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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 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.
Measured: 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
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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Oxidative Stress Biomarker Low-density Lipoprotein (LDL) Over 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.
Measured: Baseline, 6 weeks, 12 weeks
Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 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.
Measured: Baseline, 6 weeks, 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2016Jun 2017

First posted17 Sep 2015 (estimated)
Study startMar 2016
Primary completionJun 2017
Study completionJun 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02552888
Sponsor's protocol ID: TulaneU
Other IDs: 1U54GM104940
Acronym: NICE
Status last verified: Mar 2021
First submitted: 10 Sep 2015
Last updated: 20 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: deidentified data sets may be available to other researchers.

Publications

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.
PubMed 37916745
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.
PubMed 33023894

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 20 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Nitrite, Isoquercetin and Endothelial Dysfunction (NICE) Trial
ClinicalTrials.gov ID: NCT02552888
Acronym / sponsor ID: NICE / TulaneU
Conditions: Chronic Kidney Disease
Keywords: Endothelial Dysfunction, Inflammation, Oxidative Stress, eGFR, Urine Albumin
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: Tulane UniversityUniversity, hospital or other
Collaborators: National Institute of General Medical Sciences (NIGMS)
Study start: Mar 2016
Primary completion: Jun 2017 (actual)
Study completion: Jun 2017 (actual)
First posted: 17 Sep 2015 (estimated)
Results: Posted 20 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
treatment	Experimental	Drug: Immediate release sodium nitrite, Dietary Supplement: IsoquercetinImmediate release sodium nitrite 40 mg by mouth twice per day and Isoquercetin 225 mg by mouth once per day.
Placebos	Placebo comparator	Other: placebosidentical placebos.

Who may qualify

Ages: 21 to 74 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (25 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Immediate release sodium nitriteAlso: TV1001Immediate release sodium nitrite 40 mg by mouth twice per day	Drug	treatment
IsoquercetinAlso: 3-O-glucosideIsoquercetin 225 mg by mouth once per day	Dietary supplement	treatment
placebosplacebos	Other	Placebos

Primary outcome

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.

9 secondary outcomes

Mean Change in Endothelial Function Biomarkers VCAM-1, ICAM-1, E-selectin and vWF Over 12 Weeks
Time frame: Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Asymmetrical DiMethylArginine (ADMA) Over 12 Weeks
Time frame: Baseline, 6 weeks, 12 weeks
Mean Change in Endothelial Function Biomarker Endostatin Over 12 Weeks
Time frame: 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
Mean Change in Inflammatory Biomarker C-Reactive Protein (CRP) Over 12 Weeks
Time frame: 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
Mean Change in Inflammatory Biomarker Interleukin-6 (IL-6) Over 12 Weeks
Time frame: 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
Mean Change in Oxidative Stress Biomarker Nitrotyrosine Over 12 Weeks
Time frame: Baseline, 6 weeks, 12 weeks

Results and safety

Results posted to the registry on 20 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment	35	34
Placebos	35	34

Primary outcome: Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks

Time frame: Baseline, 6 weeks, 12 weeks. Mean (95% Confidence Interval). Unit: Percentage change

Measure	Treatment n = 35	Placebos n = 35
Value	1.1 (-0.1 to 2.3)	0.3 (-0.9 to 1.5)

Population analysed: Mean Changes Over 12 Weeks (95% CI)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Each participant was assessed for adverse events in the duration of 3 months.. Other adverse events reported at 1.75% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment	1 of 35 (2.9%)	11 of 35 (31.4%)	0 of 35
Placebos	1 of 35 (2.9%)	14 of 35 (40%)	0 of 35

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 37916745Colombijn 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.
Derived from this study: PubMed 33023894Chen 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.
Individual participant dataSharing planned: Yes. deidentified data sets may be available to other researchers.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jing Chen, MD principal investigator

Tulane University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Immediate release sodium nitrite and Isoquercetin in people with Chronic Kidney Disease, run by Tulane University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Percentage Change in Endothelium-dependent Flow-mediated Vasodilation (FMD) Over 12 Weeks (time frame: Baseline, 6 weeks, 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02552888, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021.