CClinicalTrials.gg
CompletedNCT03370991Updated Sep 14, 2022

Blueberries for Improving Vascular Endothelial Function in Postmenopausal Women With Elevated Blood Pressure

An interventional study of Blueberry Powder and Placebo Powder in Menopause, Elevated Blood Pressure and Hypertension, sponsored by Colorado State University. Completed at 1 site in United States. Open to female participants aged 45 Years to 65 Years. Per ClinicalTrials.gov, last updated 2022-09-14.

Sponsored by Colorado State University · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
43
Allocation
Randomized
Ages
45 Years to 65 Years
Sex
Female
01

Study summary

Postmenopausal women are at an increased risk of developing cardiovascular disease (CVD) largely due to accelerated aging-related modifications to vascular health following menopause. The vascular endothelium is responsible for producing chemicals that are essential for proper vasodilation and blood flow and therefore is involved in maintaining normal blood pressure. A major modification that occurs during aging and is accelerated during menopause is termed vascular endothelial dysfunction which is characterized by impaired endothelium-dependent dilation. This can lead to increased blood pressure, atherosclerosis, and increased risk of CVD and death. Nitric oxide (NO) is a chemical produced by the endothelium and is essential for normal endothelial function and cardiovascular health. Vascular endothelial dysfunction is primarily caused by reduced NO bioavailability secondary to excessive oxidative stress. Approximately 3/4 of postmenopausal women have elevated blood pressure or hypertension which further worsens endothelial function and increases CVD risk through increased oxidative stress and inflammation. Blueberries are rich in phytochemicals including anthocyanins, phenolic acids, and pterostilbene. These phytochemicals and their metabolites are known to attenuate oxidative stress and inflammation. The overall goal of the current study is to assess the efficacy of blueberries to improve vascular endothelial dysfunction in this high-risk population and to gain insight into underlying mechanisms. 58 postmenopausal women with elevated blood pressure and stage 1-HTN will be asked to consume 22 grams freeze-dried blueberry powder or placebo powder per day for 12 weeks. Vascular endothelial function will be assessed at baseline and 12 weeks. Measurements indicative of vascular nitric oxide production, oxidative stress, inflammation, cardiometabolic health, cognitive function, and blueberry phytochemical metabolism will be measured at baseline and 12 weeks. Blood pressure will be assessed at baseline and 4, 8, and 12 weeks.

02

Conditions studied

  • Menopause
  • Elevated Blood Pressure
  • Hypertension
  • Endothelial Dysfunction

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Keywords

  • Blueberries
  • Polyphenols
  • Cardiovascular Disease
  • Atherosclerosis
  • Oxidative Stress
  • Inflammmation
  • Endothelium
  • Vasodilation
  • Blood Pressure
  • Menopause
  • Women's Health
  • Functional Food
  • Bioactive Compounds
  • Dietary Supplements
  • Aging
03

Who can participate

Ages eligible
45 Years to 65 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Aged 45-65 years
  • Postmenopausal women (≥ 1 years postmenopausal; natural or surgical menopause; confirmed by measurement of estradiol at a level \< 30 pg/mL and follicle-stimulating hormone at a level ≥ 30 mIU/mL)
  • Elevated or stage 1-HTN (confirmed as resting seated systolic blood pressure \< 120 or ≥ 139 mmHg and/or a diastolic blood pressure ≥ 90 mmHg using an average of 3 measurements, on 2 separate occasions - screening and baseline visits)
  • Ability to provide informed consent

Exclusion criteria

Exclusion Criteria:

  • Systolic blood pressure \< 120 or ≥ 139 mm Hg and/or diastolic blood pressure ≥ 90 mmHg
  • Taking > 1 antihypertensive medication and/or taking the antihypertensive medication for \< 3 months
  • Diagnosed cancer, cardiovascular disease, diabetes, or gastrointestinal, kidney, liver, and/or pancreatic disease
  • Triglycerides > 350 mg/dL, low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, and/or taking a lipid-lowering medication
  • Hormone replacement therapy use 6 months prior to study start
  • Taking phosphodiesterase-5 inhibitors
  • Weight change ≥ 3 kg in the past 3 months, actively trying to lose weight, or unwilling to remain weight stable throughout the study
  • Current smokers or history of smoking in the past 12 months
  • Binge and/or heavy drinker (>3 drinks on any given occasion and/or >7 drinks/week for women, and >4 drinks on any given occasion and/or >14 drinks/week for men)
  • Body mass index \< 18.5 or > 40 kg/m2
  • Active infection or antibiotic therapy
  • Allergies or contraindication to study treatments, pharmacological agents, or procedures
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
43 participants (actual)

Study arms

  • Experimental
    Blueberry

    22 g/day freeze-dried blueberry powder for 12 weeks

    Dietary Supplement: Blueberry Powder

  • Placebo comparator
    Control

    22 g/day placebo powder for 12 weeks

    Dietary Supplement: Placebo Powder

Interventions

  • Dietary supplementBlueberry Powder

    22 g/day freeze-dried blueberry powder for 12 weeks

  • Dietary supplementPlacebo Powder

    22 g/day placebo powder for 12 weeks

05

What researchers measure

Primary outcomes

  1. Endothelium-dependent dilation

    Assessed as brachial artery flow-mediated dilation in a study subset of participants

    Time frame: Baseline to 12 Weeks

  2. Blood pressure

    Assessed using an automated blood pressure monitor (SphgmoCor)

    Time frame: Baseline to 12 weeks

Secondary outcomes

  1. Vascular oxidative stress

    Change in brachial artery flow-mediated dilation following acute infusion of ascorbic acid (a dose known to scavenge superoxide) as an index of vascular oxidative stress in a study subset of participants

    Time frame: Baseline and 12 weeks

  2. Endothelial cell nitric oxide production, oxidative stress, and inflammation

    Protein expression markers will be measured by quantitative immunofluorescence in biopsied venous endothelial cells in a study subset of participants

    Time frame: Baseline and 12 weeks

  3. Systemic markers of cardiometabolic health

    Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation

    Time frame: Baseline and 12 weeks

  4. Plasma blueberry polyphenol metabolites

    Targeted analysis of plasma metabolites by GC-MS and LC-MS

    Time frame: Baseline and 12 weeks

  5. Endothelium-independent dilation

    Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants

    Time frame: Baseline to 12 weeks

  6. Augmentation index

    Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL

    Time frame: Baseline to 12 weeks

  7. Pulse wave velocity

    Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL

    Time frame: Baseline to 12 weeks

  8. Gut microbiota

    Determine the effects on stool sample microbial populations

    Time frame: Baseline to 12 weeks

Other outcomes

  1. Processing speed

    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

    Time frame: Baseline and 12 weeks

  2. Language

    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

    Time frame: Baseline and 12 weeks

  3. Working memory

    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

    Time frame: Baseline and 12 weeks

  4. Executive function and attention

    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

    Time frame: Baseline and 12 weeks

  5. Episodic memory

    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

    Time frame: Baseline and 12 weeks

  6. Peripheral blood mononuclear cell inflammation and oxidative stress

    Exploratory measures analyzed by gene expression

    Time frame: Baseline and 12 weeks

06

Study locations

1 site
  • Department of Food Science and Human Nutrition, Colorado State University
    Fort Collins, Colorado 80523-1571, United States
07

References and documents

Publications

  • Johnson SA, Figueroa A, Navaei N, Wong A, Kalfon R, Ormsbee LT, Feresin RG, Elam ML, Hooshmand S, Payton ME, Arjmandi BH. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial. J Acad Nutr Diet. 2015 Mar;115(3):369-377. doi: 10.1016/j.jand.2014.11.001. Epub 2015 Jan 8. PubMed 25578927 ↗

Related links

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03370991
Lead sponsor
Colorado State University
Collaborators
U.S. Highbush Blueberry Council
Responsible party
Sarah Johnson (Assistant Professor, Colorado State University) — Principal investigator
First posted
Dec 13, 2017
Start date
Dec 2, 2017
Primary completion
Sep 30, 2021
Completion
Sep 30, 2021
Last update
Sep 14, 2022

Study contacts

Sarah A. Johnson, PhD, RDN
principal investigator · Department of Food Science and Human Nutrition, Colorado State University

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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