Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study

NCT03617302 | Completed Early Phase 1 Results DMC FDA Drug

• 1 other identifier: 201805720
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Aging; Endothelial Dysfunction; Arterial Stiffness; 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

Outcome Measures

Primary Outcomes (3)

• Change in Carotid Artery Compliance in mm/mmHg x 10-1

  Common carotid artery compliance measured by ultrasonography and applanation tonometry. Carotid compliance is the change in carotid diameter per change in carotid pulse pressure.

  Baseline and 2 hours following nitrate-depleted placebo beetroot juice or nitrate-containing beetroot juice

• Change in Carotid Augmentation Index

  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.

  Baseline and 2 hours following nitrate-depleted beetroot juice or nitrate-containing beetroot juice

• Change in Carotid Pulse Pressure in mmHg

  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.

  Baseline and 2 hours following nitrate-depleted beetroot juice or nitrate-containing beetroot juice

Study Arms (2)

Beetroot juice

ACTIVE COMPARATOR

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

Drug: Experimental: Nitrate-containing

Placebo Beetroot juice

PLACEBO COMPARATOR

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

Drug: Placebo: Nitrate-depleted

Interventions

Placebo: Nitrate-depleted DRUG

Placebo

Placebo Beetroot juice

Experimental: Nitrate-containing DRUG

Experimental

Beetroot juice

Eligibility Criteria

• Age: 50 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gary L. Pierce, PhD: lead
• University of Wisconsin, Madison: collaborator

Study Sites (1)

University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Hypertension; Cognitive Dysfunction; Cerebral Small Vessel Diseases

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Dr. Gary Pierce
• Organization: University of Iowa

gary-pierce@uiowa.edu

319-335-9487

Study Officials

• Gary Pierce, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: July 30, 2018
• First Posted: August 6, 2018
• Study Start: November 1, 2018
• Primary Completion: December 30, 2022
• Study Completion: June 30, 2024
• Last Updated: March 4, 2026
• Results First Posted: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)