AgingEarly Phase 1INCANCT03617302
Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
A Early Phase 1 study testing Experimental: Nitrate-containing in people with Aging and Arterial Stiffness, run by Gary L. Pierce, PhD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging, Arterial Stiffness, Endothelial Dysfunction
- What is being tested?
- Experimental: Nitrate-containing
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2018to 30 Jun 2024
- Phase
- Early Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
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.
Read the 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.
- Being tested
- Experimental: Nitrate-containing, Placebo: Nitrate-depleted
- Keywords
- Carotid artery stiffness, Cerebrovascular function, Cerebral blood flow, Pulsatility, Beetroot juice, Dietary Inorganic Nitrate Supplementation, Cerebral Small Vessel Disease, Cerebrovascular Reserve, Neurovascular Coupling
- Medical subject headings
- Hypertension, Cognitive Dysfunction, Cerebral Small Vessel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental: Nitrate-containingDrug
Experimental
Placebo: Nitrate-depletedDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Beetroot juice | Active comparator | 10-grams of nitrate-containing beetroot concentrate diluted in 120-180 milliliters of water. Receives: 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. Receives: Drug: Placebo: Nitrate-depleted |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline and 2 hours following nitrate-depleted beetroot juice or nitrate-containing beetroot juice
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2018
- Study start1 Nov 2018
- Primary completion30 Dec 2022
- Study completion30 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AgingStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gary L. Pierce, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- University of Wisconsin, Madison
- Responsible party
- Sponsor-investigator, Gary L. Pierce, PhD, University of Iowa
- Investigators
- Gary Pierce, PhD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03617302
- Sponsor's protocol ID
- 201805720
- Acronym
- INCA
- Status last verified
- Feb 2026
- First submitted
- 30 Jul 2018
- Last updated
- 4 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No