Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study (INCA)

• ClinicalTrials.gov Identifier: NCT03617302
• Recruitment Status: Recruiting
• First Posted: August 6, 2018
• Last Update Posted: April 30, 2021
• Sponsor: Gary L. Pierce
• Collaborator: University of Wisconsin, Madison
• Information provided by (Responsible Party): Gary L. Pierce, University of Iowa

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Aging; Arterial Stiffness; Endothelial Dysfunction; Hypertension; Cognitive Decline	Drug: Experimental: Nitrate-containing; Drug: Placebo: Nitrate-depleted	Early Phase 1

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 (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
• Actual Study Start Date: November 1, 2018
• Estimated Primary Completion Date: June 30, 2022
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Beetroot juice; 10-grams of nitrate-containing beetroot concentrate diluted in 120-180 milliliters of water.	Drug: Experimental: Nitrate-containing; Experimental
Placebo Comparator: Placebo Beetroot juice; 10 grams of nitrate-depleted beetroot concentrate balanced for anti-oxidant content diluted in 120-180 milliliters of water.	Drug: Placebo: Nitrate-depleted; Placebo

Outcome Measures

Primary Outcome Measures :

1. Acute change in carotid artery stiffness [ Time Frame: 2-hours ]
   Common carotid artery stiffness measured by ultrasonography and applanation tonometry.
2. Acute change in cerebral blood flow [ Time Frame: 2-hours ]
   Large cerebral artery blood flow will be measured using 4-Dimensional (4D) phase contrast vastly undersampled isotropic projection imaging (pcVIPR) magnetic resonance imaging (MRI).

Secondary Outcome Measures :

1. Internal carotid artery endothelium-dependent dilation [ Time Frame: 2-hours ]
   Endothelium-dependent dilation of the internal carotid artery in response to hypercapnia will be measured using ultrasonography.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Contacts

Contact: Gary L Pierce, PhD; (319)335-9487; gary-pierce@uiowa.edu

Contact: Amy Stroud, RN; (319)356-2710 ext 3193562710; amy-stroud@uiowa.edu

Locations

United States, Iowa

University of Iowa; Recruiting

Iowa City, Iowa, United States, 52242

Contact: Gary L Pierce, PhD gary-pierce@uiowa.edu

Contact: Amy Stroud, RN 3193562710 amy-stroud@uiowa.edu

Sponsors and Collaborators

Gary L. Pierce

University of Wisconsin, Madison

Investigators

• Principal Investigator: Gary Pierce, PhD; University of Iowa

More Information

• Responsible Party: Gary L. Pierce, Principle Investigator, University of Iowa
• ClinicalTrials.gov Identifier: NCT03617302
• Other Study ID Numbers: 201805720
• First Posted: August 6, 2018
• Last Update Posted: April 30, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Gary L. Pierce, University of Iowa:

Carotid artery stiffness; Cerebrovascular function; Cerebral blood flow; Pulsatility; Beetroot juice; Dietary Inorganic Nitrate Supplementation; Cerebral Small Vessel Disease; Cerebrovascular Reserve; Neurovascular Coupling

Additional relevant MeSH terms:

Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders