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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03370991
Recruitment Status : Active, not recruiting
First Posted : December 13, 2017
Last Update Posted : April 19, 2021
Sponsor:
Collaborator:
U.S. Highbush Blueberry Council
Information provided by (Responsible Party):
Sarah Johnson, Colorado State University

Tracking Information
First Submitted Date  ICMJE December 2, 2017
First Posted Date  ICMJE December 13, 2017
Last Update Posted Date April 19, 2021
Actual Study Start Date  ICMJE December 2, 2017
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2020)
  • Endothelium-dependent dilation [ Time Frame: Baseline to 12 Weeks ]
    Assessed as brachial artery flow-mediated dilation in a study subset of participants
  • Blood pressure [ Time Frame: Baseline to 12 weeks ]
    Assessed using an automated blood pressure monitor (SphgmoCor)
Original Primary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • Endothelium-dependent dilation [ Time Frame: Baseline ]
    Assessed as brachial artery flow-mediated dilation
  • Endothelium-dependent dilation [ Time Frame: 12 weeks ]
    Assessed as brachial artery flow-mediated dilation
  • Endothelium-independent dilation [ Time Frame: Baseline ]
    Assessed as brachial artery diameter responses to sublingual nitroglycerin
  • Endothelium-independent dilation [ Time Frame: 12 weeks ]
    Assessed as brachial artery diameter responses to sublingual nitroglycerin
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 26, 2020)
  • 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
  • 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
  • Systemic markers of cardiometabolic health [ Time Frame: Baseline and 12 weeks ]
    Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation
  • Plasma blueberry polyphenol metabolites [ Time Frame: Baseline and 12 weeks ]
    Targeted analysis of plasma metabolites by GC-MS and LC-MS
  • Endothelium-independent dilation [ Time Frame: Baseline to 12 weeks ]
    Assessed as brachial artery diameter responses to sublingual nitroglycerin in a study subset of participants
  • Augmentation index [ Time Frame: Baseline to 12 weeks ]
    Arterial stiffness assessed as augmentation index using the SphygmoCor XCEL
  • Pulse wave velocity [ Time Frame: Baseline to 12 weeks ]
    Arterial stiffness assessed as carotid-femoral pulse wave velocity using the SphygmoCor XCEL
  • Gut microbiota [ Time Frame: Baseline to 12 weeks ]
    Determine the effects on stool sample microbial populations
Original Secondary Outcome Measures  ICMJE
 (submitted: December 7, 2017)
  • 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
  • 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
  • Systemic markers of cardiometabolic health [ Time Frame: Baseline and 12 weeks ]
    Circulating markers of lipid and glucose metabolism, nitric oxide, and inflammation
  • Plasma blueberry polyphenol metabolites [ Time Frame: Baseline and 12 weeks ]
    Targeted analysis of plasma metabolites by GC-MS and LC-MS
  • Peripheral blood mononuclear cell inflammation and oxidative stress [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures analyzed by flow cytometry
  • Episodic memory [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Executive function and attention [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Working memory [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Language [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Processing speed [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
Current Other Pre-specified Outcome Measures
 (submitted: January 26, 2020)
  • Processing speed [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Language [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Working memory [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Executive function and attention [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Episodic memory [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures assessed using the NIH Cognitive Toolbox iPad app
  • Peripheral blood mononuclear cell inflammation and oxidative stress [ Time Frame: Baseline and 12 weeks ]
    Exploratory measures analyzed by gene expression
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Blueberries for Improving Vascular Endothelial Function in Postmenopausal Women With Elevated Blood Pressure
Official Title  ICMJE Blueberry Consumption for Improving Vascular Endothelial Dysfunction in Postmenopausal Women With Elevated Blood Pressure and Stage 1-Hypertension
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Menopause
  • Elevated Blood Pressure
  • Hypertension
  • Endothelial Dysfunction
Intervention  ICMJE
  • Dietary Supplement: Blueberry Powder
    22 g/day freeze-dried blueberry powder for 12 weeks
  • Dietary Supplement: Placebo Powder
    22 g/day placebo powder for 12 weeks
Study Arms  ICMJE
  • Experimental: Blueberry
    22 g/day freeze-dried blueberry powder for 12 weeks
    Intervention: Dietary Supplement: Blueberry Powder
  • Placebo Comparator: Control
    22 g/day placebo powder for 12 weeks
    Intervention: Dietary Supplement: Placebo Powder
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 7, 2017)
58
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2021
Estimated Primary Completion Date September 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Postmenopausal women
Ages  ICMJE 45 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03370991
Other Study ID Numbers  ICMJE 1255927
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sarah Johnson, Colorado State University
Study Sponsor  ICMJE Colorado State University
Collaborators  ICMJE U.S. Highbush Blueberry Council
Investigators  ICMJE
Principal Investigator: Sarah A. Johnson, PhD, RDN Department of Food Science and Human Nutrition, Colorado State University
PRS Account Colorado State University
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP