Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study

NCT ID: NCT03617302

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-01
• Study Completion Date: 2024-06-30

Brief Summary

This study investigates the effect of dietary inorganic nitrate supplementation on 1) large elastic artery stiffness and hemodynamics and 2) cerebrovascular function in middle-aged and older adults. Participants will be randomized to consume either nitrate-containing or nitrate-depleted beetroot juice.

Detailed Description

Reduced nitric oxide bioavailability with aging contributes in part to increased large central artery stiffness and cerebrovascular dysfunction. Large central artery stiffness is a risk factor for cognitive decline mediated in part by the development of cerebrovascular dysfunction. This study will investigate the degree to which improving nitric oxide bioavailability using dietary inorganic nitrate supplementation improves cerebrovascular function through reductions in large central artery stiffness in middle-aged and older adults.

Conditions

Aging; Arterial Stiffness; Endothelial Dysfunction; Hypertension; Cognitive Decline

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Beetroot juice

10-grams of nitrate-containing beetroot concentrate diluted in 120-180 milliliters of water.

Group Type: EXPERIMENTAL

Experimental: Nitrate-containing

Intervention Type: DRUG

Experimental

Placebo Beetroot juice

10 grams of nitrate-depleted beetroot concentrate balanced for anti-oxidant content diluted in 120-180 milliliters of water.

Group Type: PLACEBO_COMPARATOR

Placebo: Nitrate-depleted

Intervention Type: DRUG

Placebo

Interventions

Experimental: Nitrate-containing

Experimental

Intervention Type: DRUG

Placebo: Nitrate-depleted

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age 50-79 years
• Cognitively healthy, having mild cognitive impairment
• Able to undergo cardiovascular testing procedures including fasting overnight and holding selected morning medication doses.
• Ability to understand and willingness to sign a written informed consent document.
• Ability to lie comfortably for up to 90 minutes
• Women only: Post-menopausal

Exclusion Criteria

• Current or history of cardiovascular disease disease (heart attack, stroke, heart failure, cardiomyopathy or peripheral artery disease, heart angioplasty/stent or bypass surgery, valve replacement, carotid endarterectomy, heart transplant.
• Medical history of stroke or other neurological disorder or systemic illness that could potentially affect cognition or brain function (outside of a diagnosis of Mild Cognitive impairment, Alzheimer's Disease) or could affect their safety or comfort while undergoing the imaging or cardiovascular studies.
• Subjects with evidence of cardiovascular disease at baseline or during the exercise test (evidence of myocardial infarction, abnormal cardiac arrhythmia, myocardial ischemia, conduction delays, >1mm S-T segment depression or elevation; >3 beat ventricular tachycardia; atrial fibrillation) will be excluded from the study.
• Wilson's disease, hemochromatosis
• Individuals taking clonidine or other short-acting beta blocker
• Resting blood pressure > 200/ 110 mmHg or systolic <90 mmHg
• Medical history of chronic major psychiatric or current diagnosis of major psychiatric disease (other than dementia).
• Systemic illness or neurological disorder potentially affecting cognition or cerebral blood flow other than mild cognitive impairment
• Unable to provide informed consent due to cognitive impairment
• Currently taking medications that may affect cerebral blood flow (e.g. papaverine, indomethacin, acetazolamide, etc) or efficacy of beetroot juice (proton pump inhibitors)
• Current clinically abnormal thyroid function not adequately regulated by thyroid hormone supplementation or medication.
• Allergic to beets
• Current tobacco user or history of tobacco use within the past 3 months (cigarettes, cigars, chewing tobacco, hookah, electronic cigarettes) or living with someone who smokes/has smoked in the past 3 months.
• Current diagnosis of insulin-dependent diabetes (Type I or insulin dependent Type II)
• Current diagnosis of chronic obstructive lung disease, cystic fibrosis, emphysema, chronic bronchitis
• History of renal failure, dialysis or kidney transplant
• Current diagnosis or history of liver disease or HIV/AIDS, or cancer (other than non-melanoma skin cancers).
• Current diagnosis or history of rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis
• Vulnerable populations (prisoners, etc) will not be eligible.
• Unwillingness to wash out from a vitamin or dietary supplement regime prior to enrollment and maintain throughout the duration of the study.
• Inability to comply with experimental instructions.
• Uncontrolled intercurrent illness that would limit compliance with study requirements per investigator.
• Inability to fast or hold morning medications doses until after testing is complete.
• Hormone replacement use within the past 6 months
• Currently enrolled in another study using an study medication, supplement, device or intervention.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Wisconsin, Madison

OTHER

Sponsor Role: collaborator

Gary L. Pierce

OTHER

Sponsor Role: lead

Responsible Party

Gary L. Pierce

Principle Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Gary Pierce, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

Other Identifiers

201805720

Identifier Type: -

Identifier Source: org_study_id