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

Primary Purpose

Aging, Arterial Stiffness, Endothelial Dysfunction

Status
Active
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Experimental: Nitrate-containing
Placebo: Nitrate-depleted
Sponsored by
Gary L. Pierce
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aging focused on measuring Carotid artery stiffness, Cerebrovascular function, Cerebral blood flow, Pulsatility, Beetroot juice, Dietary Inorganic Nitrate Supplementation, Cerebral Small Vessel Disease, Cerebrovascular Reserve, Neurovascular Coupling

Eligibility Criteria

50 Years - 79 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University of Iowa

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Beetroot juice

Placebo Beetroot juice

Arm Description

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

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

Outcomes

Primary Outcome Measures

Acute change in carotid artery stiffness
Common carotid artery stiffness measured by ultrasonography and applanation tonometry.
Acute change in cerebral blood flow
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

Full Information

First Posted
July 30, 2018
Last Updated
May 22, 2023
Sponsor
Gary L. Pierce
Collaborators
University of Wisconsin, Madison
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1. Study Identification

Unique Protocol Identification Number
NCT03617302
Brief Title
Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
Acronym
INCA
Official Title
Effects of Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 1, 2018 (Actual)
Primary Completion Date
December 30, 2022 (Actual)
Study Completion Date
June 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Gary L. Pierce
Collaborators
University of Wisconsin, Madison

4. Oversight

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
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Beetroot juice
Arm Type
Experimental
Arm Description
10-grams of nitrate-containing beetroot concentrate diluted in 120-180 milliliters of water.
Arm Title
Placebo Beetroot juice
Arm Type
Placebo Comparator
Arm Description
10 grams of nitrate-depleted beetroot concentrate balanced for anti-oxidant content diluted in 120-180 milliliters of water.
Intervention Type
Drug
Intervention Name(s)
Experimental: Nitrate-containing
Intervention Description
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo: Nitrate-depleted
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Acute change in carotid artery stiffness
Description
Common carotid artery stiffness measured by ultrasonography and applanation tonometry.
Time Frame
2-hours
Title
Acute change in cerebral blood flow
Description
Large cerebral artery blood flow will be measured using 4-Dimensional (4D) phase contrast vastly undersampled isotropic projection imaging (pcVIPR) magnetic resonance imaging (MRI).
Time Frame
2-hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gary Pierce, PhD
Organizational Affiliation
University of Iowa
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Inorganic Nitrate Supplementation on Cerebrovascular Aging and Arterial Stiffness Study

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