Effects of Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
Trial Snapshot
- Phase
- Early Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Change in Carotid Augmentation Index
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 50 Years to 79 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
Beetroot juice
10-grams of nitrate-containing beetroot concentrate diluted in 120-180 milliliters of water.
Intervention: Experimental: Nitrate-containing (Drug)
Placebo Beetroot juice
10 grams of nitrate-depleted beetroot concentrate balanced for anti-oxidant content diluted in 120-180 milliliters of water.
Intervention: Placebo: Nitrate-depleted (Drug)
Outcomes
Primary Outcomes
Change in Carotid Augmentation Index
Time Frame: Baseline and 2 hours following nitrate-depleted beetroot juice or nitrate-containing beetroot juice
Carotid Augmentation Index is calculated as the augmentation pressure divided by the pulse pressure, and expressed as a percentage. Higher augmentation index percentage is a worse outcome than lower percentage.
Change in Carotid Artery Compliance in mm/mmHg x 10-1
Time Frame: Baseline and 2 hours following nitrate-depleted placebo beetroot juice or nitrate-containing beetroot juice
Common carotid artery compliance measured by ultrasonography and applanation tonometry. Carotid compliance is the change in carotid diameter per change in carotid pulse pressure.
Change in Carotid Pulse Pressure in mmHg
Time Frame: Baseline and 2 hours following nitrate-depleted beetroot juice or nitrate-containing beetroot juice
Carotid pulse pressure measured by carotid tonometry calibrated to brachial mean and diastolic pressure. Carotid pulse pressure is the difference between carotid systolic blood pressure and diastolic blood pressure.
Secondary Outcomes
No secondary outcomes reported
Investigators
Gary L. Pierce, PhD
Principle Investigator
University of Iowa