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

Primary Purpose

Chronic Kidney Disease

Status

Recruiting

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Nitrate-rich beetroot juice

Nitrate-depleted beetroot juice

About this trial

This is an interventional other trial for Chronic Kidney Disease

Eligibility Criteria

30 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Integrative Physiology of Aging LaboratoryRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Nitrate-rich beetroot juice

Nitrate-depleted beetroot juice

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Change in vascular endothelial function

as measured by brachial artery flow-mediated dilation

Change in aortic stiffness

as measured by carotid-femoral pulse wave velocity

Secondary Outcome Measures

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

Change in endothelial cell markers of oxidative stress

Endothelial cell nitrotyrosine levels will be determined

Full Information

NCT ID

NCT03826147

First Posted

January 28, 2019

Last Updated

May 15, 2023

Sponsor

University of Colorado, Boulder

1. Study Identification

Unique Protocol Identification Number

NCT03826147

Brief Title

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

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 1, 2019 (Actual)

Primary Completion Date

July 2023 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Colorado, Boulder

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Disease

7. Study Design

Primary Purpose

Other

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Double-blind

Allocation

Randomized

Enrollment

92 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nitrate-rich beetroot juice

Arm Type

Active Comparator

Arm Description

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

Arm Title

Nitrate-depleted beetroot juice

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

Nitrate-rich beetroot juice

Intervention Description

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

Intervention Type

Dietary Supplement

Intervention Name(s)

Nitrate-depleted beetroot juice

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in vascular endothelial function

Description

as measured by brachial artery flow-mediated dilation

Time Frame

Baseline, 3 months

Title

Change in aortic stiffness

Description

as measured by carotid-femoral pulse wave velocity

Time Frame

Baseline, 3 months

Secondary Outcome Measure Information:

Title

Change in oxidative stress-associated suppression of endothelial function assessed as the increase in brachial artery flow-mediated dilation following an ascorbic acid infusion

Description

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

Time Frame

Baseline, 3 months

Title

Change in endothelial cell markers of oxidative stress

Description

Endothelial cell nitrotyrosine levels will be determined

Time Frame

Baseline, 3 months

Other Pre-specified Outcome Measures:

Title

Motor function composite score

Description

Multiple domains of motor function (including endurance, strength, dexterity) assessed using the NIH Toolbox Motor Battery (aggregated into one reported value)

Time Frame

Baseline, 3 months

Title

Fluid cognition composite score

Description

Multiple domains of cognitive function (including executive function, memory, processing speed) assessed using the NIH Toolbox Cognitive Battery (aggregated into one reported value)

Time Frame

Baseline, 3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hannah Lally

Phone

303-735-6410

beetrootstudy@colorado.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthew J Rossman, PhD

Organizational Affiliation

University of Colorado, Boulder

Official's Role

Principal Investigator

Facility Information:

Facility Name

Integrative Physiology of Aging Laboratory

City

Boulder

State/Province

Colorado

ZIP/Postal Code

80309

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Melanie R Zigler, M.S.

Phone

303-492-2485

melanie.connell@colorado.edu

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32735111

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.

Results Reference

derived

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

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