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Early Phase 1 N=16 Randomized Double-blind Treatment

Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study

Aging · Arterial Stiffness · Endothelial Dysfunction · Hypertension · Cognitive Decline

Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Mar 2026
Primary outcome: Primary: Change in Carotid Artery Compliance in mm/mmHg x 10-1 — 0.88; 0.87; 0.90; 0.79 mm/mmHg x 10-1

Study Design & Population

Study type
Interventional
Phase
Early Phase 1
Interventions
Experimental: Nitrate-containing (Drug); Placebo: Nitrate-depleted (Drug)
Age
Adult, Older Adult · 50+ yrs
Sex
All
Sponsor
Gary L. Pierce, PhD
Primary completion
Dec 2022

Outcome Measures

OutcomeResultp-value
PRIMARY
Change in Carotid Artery Compliance in mm/mmHg x 10-1
0.88; 0.87; 0.90; 0.79
PRIMARY
Change in Carotid Augmentation Index
11; 10; 19; 17
PRIMARY
Change in Carotid Pulse Pressure in mmHg
45; 44; 48; 51

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.

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03617302). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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