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

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03826147
• Other study ID #: 18-0364
• Status: Recruiting
• Phase: Phase 4
• Start date: May 1, 2019
• Est. completion date: July 2024

Study information

• Verified date: May 2023
• Source: University of Colorado, Boulder
• Contact: Hannah Lally
• Phone: 303-735-6410
• Email: beetrootstudy[@]colorado.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: July 2024
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Nitrate-rich beetroot juice
Daily supplementation with ~100 kcal of nitrate-rich beetroot juice containing 400 mg of dietary nitrate (James White Drinks, UK).
• Nitrate-depleted beetroot juice
Daily supplementation with ~100 kcal of nitrate-depleted beetroot juice (James White Drinks, UK).

Locations

Country	Name	City	State
United States	Integrative Physiology of Aging Laboratory	Boulder	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
University of Colorado, Boulder

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Motor function composite score	Multiple domains of motor function (including endurance, strength, dexterity) assessed using the NIH Toolbox Motor Battery (aggregated into one reported value)	Baseline, 3 months
Other	Fluid cognition composite score	Multiple domains of cognitive function (including executive function, memory, processing speed) assessed using the NIH Toolbox Cognitive Battery (aggregated into one reported value)	Baseline, 3 months
Primary	Change in vascular endothelial function	as measured by brachial artery flow-mediated dilation	Baseline, 3 months
Primary	Change in aortic stiffness	as measured by carotid-femoral pulse wave velocity	Baseline, 3 months
Secondary	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	Baseline, 3 months
Secondary	Change in endothelial cell markers of oxidative stress	Endothelial cell nitrotyrosine levels will be determined	Baseline, 3 months