Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease

NCT03826147 | Active Not Recruiting Phase 4 DMC

• 1 other identifier: 18-0364
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• Change in vascular endothelial function

  as measured by brachial artery flow-mediated dilation

  Baseline, 3 months

• Change in aortic stiffness

  as measured by carotid-femoral pulse wave velocity

  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

  Baseline, 3 months

• Change in endothelial cell markers of oxidative stress

  Baseline, 3 months

Other Outcomes (2)

• Motor function composite score

  Baseline, 3 months

• Fluid cognition composite score

  Baseline, 3 months

Study Arms (2)

Nitrate-rich beetroot juice

ACTIVE COMPARATOR

Daily dose of nitrate-rich beetroot juice (70 mL) for 3 months.

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.

Dietary Supplement: Nitrate-depleted beetroot juice

Interventions

Nitrate-rich beetroot juice DIETARY_SUPPLEMENT

Daily supplementation with \~100 kcal of nitrate-rich beetroot juice containing 400 mg of dietary nitrate (James White Drinks, UK).

Nitrate-rich beetroot juice

Nitrate-depleted beetroot juice DIETARY_SUPPLEMENT

Daily supplementation with \~100 kcal of nitrate-depleted beetroot juice (James White Drinks, UK).

Nitrate-depleted beetroot juice

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Colorado, Boulder: lead

Study Sites (1)

Integrative Physiology of Aging Laboratory

Boulder, Colorado, 80309, United States

Location

Related Publications (2)

• 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.

  PMID: 41264372 DERIVED

• Jones 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.

  PMID: 32735111 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

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

Study Officials

• Matthew J Rossman, PhD

  University of Colorado, Boulder

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: February 1, 2019
• Study Start: May 1, 2019
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)