Aging, Arterial Stiffness, Cognitive Decline, Endothelial Dysfunction, Hypertension
Conditions
Keywords
Carotid artery stiffness, Cerebrovascular function, Cerebral blood flow, Pulsatility, Beetroot juice, Dietary Inorganic Nitrate Supplementation, Cerebral Small Vessel Disease, Cerebrovascular Reserve, Neurovascular Coupling
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.
Interventions
DRUGExperimental: Nitrate-containing
Experimental
DRUGPlacebo: Nitrate-depleted
Placebo
Sponsors
Gary L. Pierce, PhD
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 79 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Carotid Artery Compliance in mm/mmHg x 10-1 | 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 Augmentation Index | 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 Pulse Pressure in mmHg | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGary Pierce, PhD
University of Iowa
Participant flow
Pre-assignment details
Participants were randomly assigned to receive beetroot juice or placebo on visit one and then crossed-over to receive the other treatment on visit 2.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants |
| Age, Continuous | 63 years STANDARD_DEVIATION 6.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
None listed