Clinical trial NCT03617302: Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
Official title: Effects of Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Aging
Arterial Stiffness
Endothelial Dysfunction
Hypertension
Cognitive Decline
Keywords: Carotid artery stiffness
Cerebrovascular function
Cerebral blood flow
Pulsatility
Beetroot juice
Dietary Inorganic Nitrate Supplementation
Cerebral Small Vessel Disease
Cerebrovascular Reserve
Neurovascular Coupling
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: University of Wisconsin, Madison
First posted: 2018-08-06
Enrollment: 53
Sex: ALL
Minimum age (years): 50
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Acute change in carotid artery stiffness
timeFrame: 2-hours
measure: Acute change in cerebral blood flow
timeFrame: 2-hours
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
Study officials:
affiliation: University of Iowa
name: Gary Pierce, PhD
role: PRINCIPAL_INVESTIGATOR
References: