Chronic Kidney DiseasePhase 4NCT03826147
Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease
A Phase 4 study testing Nitrate-rich beetroot juice and Nitrate-depleted beetroot juice in people with Chronic Kidney Disease, run by University of Colorado, Boulder at 1 site in United States.
Trial summary
Nitric oxide (NO) is an essential molecule in the body that is decreased in patients with chronic kidney disease (CKD), leading to reductions in vascular, movement ("motor") and cognitive functions. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Nitrate-rich beetroot juice and Nitrate-depleted beetroot juice
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 92 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2019to Aug 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CKD stage II-IV (eGFR using the Modification of Diet in Renal Disease (MDRD) prediction equation 20-90 mL/min/1.73m2; stable renal function in the past 3 months)
- Ability to give informed consent
- Albumin > 3.0 g/dL
- Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 6 min, climb 10 stairs)
- Free from alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
- Mini-mental state examination score >21 (rationale: to screen for subjects with major cognitive impairment)
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- Blood pressure (BP) >100/60 mmHg for past 3 months (rationale: blood pressure below 100/60 mmHg may elevate the normally small risk of hypotension with nitrate supplementation)
- Not taking medications that will interfere with administered medications (e.g., sildenafil interacts with nitroglycerin)
- Body mass index (BMI) <40 kg/m2 (vascular function measurements can be inaccurate in severely obese patients)
Who cannot join
- Life expectancy <1 year
- Uncontrolled hypertension, defined as blood pressure > 160/100 mmHg in the past 3 months
- History of severe liver disease
- History of severe congestive heart failure (i.e., ejection fraction < 35%)
- History of hospitalizations within the last 3 months
- Active infection or antibiotic therapy
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- Warfarin use
- Vasculitis requiring immunosuppressive therapy within the last year
- High dietary nitrate intake or current nitrate/nitrite supplementation; hypersensitivity to nitrates or nitrites
- Glucose-6-phosphate dehydrogenase deficiency or blood methemoglobin >2%
- Unwilling to abstain from use of mouthwash or other oral hygiene practices (e.g., tongue scraping) outside of teeth brushing that disrupt the oral microbiome and would interfere with nitrate conversion to nitrite
- Blood donation within 8 weeks prior to enrolling in the study; unwilling to abstain from donating blood for 8 weeks after completing the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Integrative Physiology of Aging Laboratory
Boulder, Colorado, 80309
About this study
Nitric oxide (NO) is an essential molecule in the body that is decreased in patients with chronic kidney disease (CKD), leading to reductions in vascular, movement ("motor") and cognitive functions. This study will determine if daily oral supplementation (3 months) with a supplement that increases NO in the body, i.e., nitrate-rich beetroot juice, improves vascular, motor and cognitive function in patients with CKD; this study will also provide insight into the biological reasons (mechanisms) by which supplementation with nitrate-rich beetroot juice improves vascular function in these patients. Overall, this research will provide scientific evidence supporting the use of nitrate-rich beetroot juice for preserving physiological function and preventing co-morbid clinical conditions and disability in CKD.
- Conditions
- Chronic Kidney Disease
- Being tested
- Nitrate-rich beetroot juice, Nitrate-depleted beetroot juice
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrate-rich beetroot juiceDietary supplement
Daily supplementation with ~100 kcal of nitrate-rich beetroot juice containing 400 mg of dietary nitrate (James White Drinks, UK).
Nitrate-depleted beetroot juiceDietary supplement
Daily supplementation with ~100 kcal of nitrate-depleted beetroot juice (James White Drinks, UK).
| Study group | Role | What they receive |
|---|---|---|
| Nitrate-rich beetroot juice | Active comparator | Daily dose of nitrate-rich beetroot juice (70 mL) for 3 months. Receives: Dietary Supplement: Nitrate-rich beetroot juice |
| Nitrate-depleted beetroot juice | Placebo comparator | Daily dose of nitrate-depleted beetroot juice (70 mL) for 3 months. The nitrate-depleted beetroot juice is identical in appearance, taste and caloric content to nitrate-rich beetroot juice, but with nitrate removed. Receives: Dietary Supplement: Nitrate-depleted beetroot juice |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in vascular endothelial function
as measured by brachial artery flow-mediated dilation
Measured: Baseline, 3 months
Change in aortic stiffness
as measured by carotid-femoral pulse wave velocity
Measured: Baseline, 3 months
Secondary outcomes (2)
Change in oxidative stress-associated suppression of endothelial function assessed as the increase in brachial artery flow-mediated dilation following an ascorbic acid infusion
The influence of oxidative stress on brachial artery flow-mediated dilation will be determined by infusing a supraphysiological dose of ascorbic acid known to scavenge superoxide or isovolumic saline
Measured: Baseline, 3 months
Change in endothelial cell markers of oxidative stress
Endothelial cell nitrotyrosine levels will be determined
Measured: Baseline, 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2019
- Study start1 May 2019
- Primary completionJul 2026 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Boulder
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Douglas Seals, University of Colorado, Boulder
- Investigators
- Matthew J Rossman, PhD, Principal investigator, University of Colorado, Boulder
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03826147
- Sponsor's protocol ID
- 18-0364
- Status last verified
- Mar 2026
- First submitted
- 28 Jan 2019
- Last updated
- 31 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Oh ES, Opoku G, Darvish S, Craighead DH, Ostrow A, Rossman MJ, Steele CN, Struemph T, You Z, Seals DR, Chonchol M, Nowak KL. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD. Clin J Am Soc Nephrol. 2026 Mar 1;21(3):389-400. doi: 10.2215/CJN.0000000922. Epub 2025 Nov 20.
PubMed 41264372Jones AM, Vanhatalo A, Seals DR, Rossman MJ, Piknova B, Jonvik KL. Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance. Med Sci Sports Exerc. 2021 Feb 1;53(2):280-294. doi: 10.1249/MSS.0000000000002470.
PubMed 32735111
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT03826147
- Acronym / sponsor ID
- 18-0364
- Conditions
- Chronic Kidney Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- University of Colorado, BoulderUniversity, hospital or other
- Study start
- 1 May 2019 (actual)
- Primary completion
- Jul 2026 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 1 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Nitric oxide (NO) is an essential molecule in the body that is decreased in patients with chronic kidney disease (CKD), leading to reductions in vascular, movement ("motor") and cognitive functions. This study will determine if daily oral supplementation (3 months) with a supplement that increases NO in the body, i.e., nitrate-rich beetroot juice, improves vascular, motor and cognitive function in patients with CKD; this study will also provide insight into the biological reasons (mechanisms) by which supplementation with nitrate-rich beetroot juice improves vascular function in these patients. Overall, this research will provide scientific evidence supporting the use of nitrate-rich beetroot juice for preserving physiological function and preventing co-morbid clinical conditions and disability in CKD.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nitrate-rich beetroot juice | Active comparator | Dietary Supplement: Nitrate-rich beetroot juiceDaily dose of nitrate-rich beetroot juice (70 mL) for 3 months. |
| Nitrate-depleted beetroot juice | Placebo comparator | Dietary Supplement: Nitrate-depleted beetroot juiceDaily dose of nitrate-depleted beetroot juice (70 mL) for 3 months. The nitrate-depleted beetroot juice is identical in appearance, taste and caloric content to nitrate-rich beetroot juice, but with nitrate removed. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- CKD stage II-IV (eGFR using the Modification of Diet in Renal Disease (MDRD) prediction equation 20-90 mL/min/1.73m2; stable renal function in the past 3 months)
- Ability to give informed consent
- Albumin > 3.0 g/dL
- Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 6 min, climb 10 stairs)
- Free from alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders (DSM-V)
Key exclusion criteria (12 listed)
- Life expectancy <1 year
- Uncontrolled hypertension, defined as blood pressure > 160/100 mmHg in the past 3 months
- History of severe liver disease
- History of severe congestive heart failure (i.e., ejection fraction < 35%)
- History of hospitalizations within the last 3 months
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 |
|---|---|---|
| Nitrate-rich beetroot juiceDaily supplementation with ~100 kcal of nitrate-rich beetroot juice containing 400 mg of dietary nitrate (James White Drinks, UK). | Dietary supplement | Nitrate-rich beetroot juice |
| Nitrate-depleted beetroot juiceDaily supplementation with ~100 kcal of nitrate-depleted beetroot juice (James White Drinks, UK). | Dietary supplement | Nitrate-depleted beetroot juice |
Primary outcome
Change in vascular endothelial function
Time frame: Baseline, 3 months
as measured by brachial artery flow-mediated dilation
Change in aortic stiffness
Time frame: Baseline, 3 months
as measured by carotid-femoral pulse wave velocity
2 secondary outcomes
Change in oxidative stress-associated suppression of endothelial function assessed as the increase in brachial artery flow-mediated dilation following an ascorbic acid infusion
Time frame: Baseline, 3 months
Change in endothelial cell markers of oxidative stress
Time frame: Baseline, 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2026.
- Derived from this study: PubMed 41264372Oh ES, Opoku G, Darvish S, Craighead DH, Ostrow A, Rossman MJ, Steele CN, Struemph T, You Z, Seals DR, Chonchol M, Nowak KL. Sex Differences in Dementia and Mild Cognitive Impairment in Nondialysis CKD. Clin J Am Soc Nephrol. 2026 Mar 1;21(3):389-400. doi: 10.2215/CJN.0000000922. Epub 2025 Nov 20.
- Derived from this study: PubMed 32735111Jones AM, Vanhatalo A, Seals DR, Rossman MJ, Piknova B, Jonvik KL. Dietary Nitrate and Nitric Oxide Metabolism: Mouth, Circulation, Skeletal Muscle, and Exercise Performance. Med Sci Sports Exerc. 2021 Feb 1;53(2):280-294. doi: 10.1249/MSS.0000000000002470.
- Individual participant dataSharing planned: No
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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.
Matthew J Rossman, PhD principal investigator
University of Colorado, Boulder
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nitrate-rich beetroot juice and Nitrate-depleted beetroot juice in people with Chronic Kidney Disease, run by University of Colorado, Boulder 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 9 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 31 Mar 2026. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Change in vascular endothelial function (time frame: Baseline, 3 months). The study lists 2 primary outcomes in all. 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 NCT03826147, 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 31 Mar 2026.