Clinical trial NCT03826147: Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease
Official title: Nitrite-boosting Therapy for Improving Physiological Function in Patients With Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Kidney Disease
Lead sponsor: University of Colorado, Boulder
Sponsor class: OTHER
First posted: 2019-02-01
Enrollment: 92
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in vascular endothelial function
timeFrame: Baseline, 3 months
measure: Change in aortic stiffness
timeFrame: Baseline, 3 months
Secondary outcomes:
measure: Change in oxidative stress-associated suppression of endothelial function assessed as the increase in brachial artery flow-mediated dilation following an ascorbic acid infusion
timeFrame: Baseline, 3 months
measure: Change in endothelial cell markers of oxidative stress
timeFrame: Baseline, 3 months
Other outcomes:
measure: Motor function composite score
timeFrame: Baseline, 3 months
measure: Fluid cognition composite score
timeFrame: Baseline, 3 months
Locations:
city: Boulder
country: United States
facility: Integrative Physiology of Aging Laboratory
state: Colorado
Study officials:
affiliation: University of Colorado, Boulder
name: Matthew J Rossman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.