Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03370991
Recruitment Status : Recruiting
First Posted : December 13, 2017
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
U.S. Highbush Blueberry Council
Information provided by (Responsible Party):
Sarah Johnson, Colorado State University

Brief 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 and vascular endothelial dysfunction at the screening visit 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.

Condition or disease Intervention/treatment Phase
Menopause Elevated Blood Pressure Hypertension Endothelial Dysfunction Dietary Supplement: Blueberry Powder Dietary Supplement: Placebo Powder Phase 2 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Blueberry Consumption for Improving Vascular Endothelial Dysfunction in Postmenopausal Women With Elevated Blood Pressure and Stage 1-Hypertension
Actual Study Start Date : December 2, 2017
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Blueberry
22 g/day freeze-dried blueberry powder for 12 weeks
Dietary Supplement: Blueberry Powder
22 g/day freeze-dried blueberry powder for 12 weeks

Placebo Comparator: Control
22 g/day placebo powder for 12 weeks
Dietary Supplement: Placebo Powder
22 g/day placebo powder for 12 weeks




Primary Outcome Measures :
  1. Endothelium-dependent dilation [ Time Frame: Baseline to 12 Weeks ]
    Assessed as brachial artery flow-mediated dilation in a study subset of participants

  2. Blood pressure [ Time Frame: Baseline to 12 weeks ]
    Assessed using an automated blood pressure monitor (SphgmoCor)


Secondary Outcome Measures :
  1. Vascular oxidative stress [ Time Frame: Baseline and 12 weeks ]
    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

  2. Endothelial cell nitric oxide production, oxidative stress, and inflammation [ Time Frame: Baseline and 12 weeks ]
    Protein expression markers will be measured by quantitative immunofluorescence in biopsied venous endothelial cells in a study subset of participants

  3. Systemic markers of cardiometabolic health [ Time Frame: Baseline and 12 weeks ]
    Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation

  4. Plasma blueberry polyphenol metabolites [ Time Frame: Baseline and 12 weeks ]
    Targeted analysis of plasma metabolites by GC-MS and LC-MS

  5. Endothelium-independent dilation [ Time Frame: Baseline to 12 weeks ]
    Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants

  6. Augmentation index [ Time Frame: Baseline to 12 weeks ]
    Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL

  7. Pulse wave velocity [ Time Frame: Baseline to 12 weeks ]
    Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL

  8. Gut microbiota [ Time Frame: Baseline to 12 weeks ]
    Determine the effects on stool sample microbial populations


Other Outcome Measures:
  1. Processing speed [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

  2. Language [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

  3. Working memory [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

  4. Executive function and attention [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

  5. Episodic memory [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app

  6. Peripheral blood mononuclear cell inflammation and oxidative stress [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures analyzed by gene expression



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   45 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Postmenopausal women
Accepts Healthy Volunteers:   No
Criteria

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)
  • Baseline vascular endothelial dysfunction defined as brachial artery flow-mediated vasodilation < 7%
  • Ability to provide informed consent

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03370991


Contacts
Layout table for location contacts
Contact: Sarah A Johnson, PhD, RDN 970-491-3807 sarah.johnson@colostate.edu

Locations
Layout table for location information
United States, Colorado
Department of Food Science and Human Nutrition, Colorado State University Recruiting
Fort Collins, Colorado, United States, 80523-1571
Contact: Sarah A Johnson, PhD, RDN    970-491-3807    sarah.johnson@colostate.edu   
Sponsors and Collaborators
Colorado State University
U.S. Highbush Blueberry Council
Investigators
Layout table for investigator information
Principal Investigator: Sarah A. Johnson, PhD, RDN Department of Food Science and Human Nutrition, Colorado State University
Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Sarah Johnson, Assistant Professor, Colorado State University
ClinicalTrials.gov Identifier: NCT03370991    
Other Study ID Numbers: 1255927
First Posted: December 13, 2017    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sarah Johnson, Colorado State University:
Blueberries
Polyphenols
Cardiovascular Disease
Atherosclerosis
Oxidative Stress
Inflammmation
Endothelium
Vasodilation
Blood Pressure
Menopause
Women's Health
Functional Food
Bioactive Compounds
Dietary Supplements
Aging
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertension
Vascular Diseases
Cardiovascular Diseases