Clinical trial NCT03370991: Blueberries for Improving Vascular Endothelial Function in Postmenopausal Women With Elevated Blood Pressure
Official title: Blueberry Consumption for Improving Vascular Endothelial Dysfunction in Postmenopausal Women With Elevated Blood Pressure and Stage 1-Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Menopause
Elevated Blood Pressure
Hypertension
Endothelial Dysfunction
Keywords: Blueberries
Polyphenols
Cardiovascular Disease
Atherosclerosis
Oxidative Stress
Inflammmation
Endothelium
Vasodilation
Blood Pressure
Menopause
Women's Health
Functional Food
Bioactive Compounds
Dietary Supplements
Aging
Lead sponsor: Colorado State University
Sponsor class: OTHER
Collaborators: name: U.S. Highbush Blueberry Council
First posted: 2017-12-13
Enrollment: 43
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.


Eligibility 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)
* 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

Primary outcomes:
measure: Endothelium-dependent dilation
timeFrame: Baseline to 12 Weeks
measure: Blood pressure
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Vascular oxidative stress
timeFrame: Baseline and 12 weeks
measure: Endothelial cell nitric oxide production, oxidative stress, and inflammation
timeFrame: Baseline and 12 weeks
measure: Systemic markers of cardiometabolic health
timeFrame: Baseline and 12 weeks
measure: Plasma blueberry polyphenol metabolites
timeFrame: Baseline and 12 weeks
measure: Endothelium-independent dilation
timeFrame: Baseline to 12 weeks
measure: Augmentation index
timeFrame: Baseline to 12 weeks
measure: Pulse wave velocity
timeFrame: Baseline to 12 weeks
measure: Gut microbiota
timeFrame: Baseline to 12 weeks
Other outcomes:
measure: Processing speed
timeFrame: Baseline and 12 weeks
measure: Language
timeFrame: Baseline and 12 weeks
measure: Working memory
timeFrame: Baseline and 12 weeks
measure: Executive function and attention
timeFrame: Baseline and 12 weeks
measure: Episodic memory
timeFrame: Baseline and 12 weeks
measure: Peripheral blood mononuclear cell inflammation and oxidative stress
timeFrame: Baseline and 12 weeks
Locations:
city: Fort Collins
country: United States
facility: Department of Food Science and Human Nutrition, Colorado State University
state: Colorado
Study officials:
affiliation: Department of Food Science and Human Nutrition, Colorado State University
name: Sarah A. Johnson, PhD, RDN
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.