The Impact of Inorganic Nitrate-rich Beetroot Juice on Microvascular Blood Flow and Cognitive Function

Study Overview
=================
Brief Summary
-----------------
Cardiovascular disease (CVD) is one of the leading causes of mortality worldwide. Inorganic nitrate found in beetroot and green leafy vegetables has been demonstrated to reduce cardiovascular disease risk factors including reducing blood pressure and the stiffness of blood vessels by increasing levels of a compound called nitric oxide. Much of the research to date has focused on the large blood vessels, and little is known about the impact of inorganic nitrate on smaller blood vessels which could be related to cognitive function. The majority of beneficial effects with inorganic nitrate have been observed within young healthy populations. However, it is known that after the menopause women are at an increased risk of cardiovascular disease and have reduced levels of nitric oxide in their body; this could also contribute to the cognitive decline also observed post-menopause. This trial will investigate the impact of inorganic nitrate from beetroot juice on the blood flow in small blood vessels and on cognitive function in postmenopausal women. The hypothesis of the study is that the nitrate in beetroot juice will increase circulating nitric oxide that will then increase blood flow in small blood vessels and improve cognitive function.

Official Title
-----------------
The Impact of Inorganic Nitrate-rich Beetroot Juice on Microvascular Blood Flow, Cognitive Function and Other Hemodynamic Outcomes in Postmenopausal Women

Conditions
-----------------
Post Menopausal

Intervention / Treatment
-----------------
* Dietary Supplement: Concentrated beetroot juice
* Dietary Supplement: Nitrate depleted beetroot juice + potassium nitrate (KNO3)
* Dietary Supplement: Nitrate depleted beetroot juice


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Apparently healthy post-menopausal women (age over 45) Able to understand information sheet and willing to comply with the study protocol and able to give informed consent Not having menstrual period for 12 months Exclusion Criteria: Blood pressure <90/60 or > 140/90 mmHg Medical history of myocardial infarction, angina, thrombosis, stroke, cancer, high cholesterol, liver, renal, respiratory or bowel diseases or diabetes or other endocrine disorder BMI>30 Any tobacco and/or nicotine users (or quit within the last 6 months) Current use of antihypertensive medication Alcohol intake > 14 units/week Vigorous exercise > 3 times/ week Antihypertensive medication users People who have had hysterectomy Currently taking hormone replacement therapy or selective oestrogen receptor modulator

Ages Eligible for Study
-----------------
Minimum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Concentrated beetroot juice<br> | Dietary Supplement: Concentrated beetroot juice<br>* Subjects will consume 70ml shot (Beet-it Sport nitrate 400 shot, James White Drinks) and this drink contains 0.4g inorganic nitrate<br>|
| Active Comparator: Nitrate depleted beetroot juice + potassium nitrate (KNO3)<br> | Dietary Supplement: Nitrate depleted beetroot juice + potassium nitrate (KNO3)<br>* Nitrate-depleted beetroot juice (70ml) and 0.4g KNO3- will be mixed. (Same appearance and taste with Beet-it sport shot)<br>|
| Placebo Comparator: Nitrate-depleted beetroot juice<br> | Dietary Supplement: Nitrate depleted beetroot juice<br>* Subjects will consume 70ml of (Beet-it Placebo shot, James White Drinks). This drink is the same as the Beet-it Sport nitrate shot but has the nitrate removed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline endothelial dependent microvascular function as laser Doppler imaging (LDI) with iontophoresis | Measurements will be taken by LDI with iontophoresis of endothelium-dependent (acetylcholine (ACh)) | At baseline (t= 0.5 hours) and t= 3 hours | 
| Change from baseline endothelial independent microvascular function as laser Doppler imaging (LDI) with iontophoresis | Measurements will be taken by LDI of endothelium-independent (sodium nitroprusside (SNP)) | At baseline (t= 0.5 hours) and t= 3 hours | 
| Change from baseline cognitive function. Domain: Episodic memory | -Rey Auditory Verbal Learning Test (RAVLT) task Cognitive domains will be assessed by using the Gorilla online research tools. | At baseline (t= 0 hours) and t=2.5 hours | 
| Change from baseline cognitive function. Domain: Executive function 1 | -Digit Span Task | At baseline (t= 0 hours) and t=2.5 hours | 
| Change from baseline cognitive function. Domain: Executive function 2 | -Stroop Task | At baseline (t= 0 hours) and t=2.5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in blood pressure | Systolic and Diastolic Blood pressure measurement by automated device | [Time Frame: At baseline (t= 0 hours) and 15 minute intervals until t= 2.5 hours.] | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Beetroot, NO, Nitrate, Microvascular function, Cognition