Cardiovascular Health Arterial Stiffness Raspberry and Microbiome (CHARM)

Study Overview
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Brief Summary
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In this study, the investigators aim to determine the health benefits of red raspberry ellagitannin consumption on cardiovascular health. The study population is stratified according to the urolithin metabotypes (gut-microbial metabolic profile): UM-0, UM-A and UM-B. The investigators will evaluate changes in blood pressure, endothelial function, arterial stiffness, lipid profile, cognitive performance and gut microbiome composition.

Detailed Description
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Red raspberries are a good source of polyphenols including ellagitannins. Previous work suggests that urolithins, gut microbial metabolites derived from ellagitannins contained in raspberries, can improve vascular health. It has also been observed that the capacity of the gut microbiome to metabolize urolithins can influence the cardiometabolic response to ellagitannin consumption. In this work the investigators aim to investigate whether urolithin metabotypes (UM-A, B and 0) can influence the vascular response to a (poly)phenol-rich breakfast containing red raspberry ellagitannins in a healthy UK population. You will be stratified by metabotype in a first phase (NCT03573414) and are then randomly allocated to treatment or placebo. Outcomes are measured at baseline and after 12 weeks consumption of the study product.

Official Title
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Cardiovascular Health Arterial Stiffness Raspberry and Microbiome (CHARM)

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Dietary Supplement: Red Raspberry Ellagitannin Extract
* Dietary Supplement: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men or women aged 20-70 years old BMI between 18.5-35 kg/m² Normotensive: SBP lower than 140 mmHg or DBP lower than 90 mmHg Willing to maintain their normal eating/drinking habits and exercise habits to avoid changes in body weight over the duration of the study Able to understand the nature of the study Able to give signed written informed consent Exclusion Criteria: Have required treatment for hypertension at any time (e.g. statins, aspirin, blood pressure lowering drugs) BMI outside range Manifest cardiovascular disease including coronary artery disease, cerebrovascular disease and peripheral artery disease Currently treated with a diet Chronic-acute disease Unstable psychological condition Diabetes mellitus, metabolic syndrome, acute inflammation, terminal renal failure, malignancies or abnormal heart rhythm (lower or higher than 60-100 bpm) History of cancer, myocardial infarction, cerebrovascular incident or kidney abnormality Allergies to berries, flax seeds and soy milk or other significant food allergy Requiring chronic antimicrobial or antiviral treatment Reported having taken food supplements, dietary supplement or herbal remedies within 1 month of study start Weight loss of more than 10% body weight in the previous 6 months Reported participant in another study within one month before the study start Smoke an irregular amount of cigarettes per day or planning to quit smoking in the next 3 months Unable to tolerate breakfast ingestion Pregnant woman/ lactating woman/ woman planning to become pregnant/ premenopausal women who do not have a regular menstrual cycle/ premenopausal women who do not have adequate method of contraception Any reason or condition that in the judgment of the clinical investigator(s) may put the subject at unacceptable risk or that may preclude the subject from understanding or complying with the study's requirements Unable to swallow the capsule.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind placebo randomized controlled trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metabotype A<br>Taking treatment | Dietary Supplement: Red Raspberry Ellagitannin Extract<br>* Purified red raspberries ellagitannins extract 560 mg (4 capsules/day)<br>|
| Active Comparator: Metabotype B<br>Taking treatment | Dietary Supplement: Red Raspberry Ellagitannin Extract<br>* Purified red raspberries ellagitannins extract 560 mg (4 capsules/day)<br>|
| Active Comparator: Metabotype 0<br>Taking treatment | Dietary Supplement: Red Raspberry Ellagitannin Extract<br>* Purified red raspberries ellagitannins extract 560 mg (4 capsules/day)<br>|
| Placebo Comparator: Placebo<br>Taking matching placebo | Dietary Supplement: Matching Placebo<br>* Placebo treatment matching intervention (no ellagitannin) 560 mg (4 capsules/day)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in flow-mediated dilation (FMD) | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on flow-mediated dilation at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in office blood pressure | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on office systolic and diastolic blood pressure, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in heart rate | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on heart rate, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in blood flow velocity | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on blood flow velocity at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in pulse wave velocity (PWV) | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on pulse wave velocity (PWV) using a Sphygmocor device, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in augmentation Index (AIx) | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on augmentation Index (AIx) using a Sphygmocor device, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in blood lipid concentrations | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on blood lipids (Total, HDL and LDL cholesterol, triglycerides), at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in blood inflammatory markers (circulating concentrations) | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on blood inflammatory markers (CRP, IL-6), at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in 24-hour heart rate | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on 24-hour heart rate, using a monitor, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in 24-hour ambulatory blood pressure | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on 24-hour ambulatory blood pressure (SBP and DBP), using a monitor, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 
| Change in 24-hour AIx and PWV | Determine the effect of the Red raspberry ellagitannin extract vs Placebo on 24-hour arterial stiffness (AIx and PWV), using a monitor, at 12 weeks post consumption | Baseline vs 12 weeks post-consumption | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular system, Polyphenols