Clinical trial NCT04087278: Cardiovascular Health Arterial Stiffness Raspberry and Microbiome (CHARM)
Official title: Cardiovascular Health Arterial Stiffness Raspberry and Microbiome (CHARM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: Cardiovascular system
Polyphenols
Lead sponsor: King's College London
Sponsor class: OTHER
Collaborators: name: Centro de Edafología y Biología Aplicada del Segura
name: Washington Red Raspberry Commission
First posted: 2019-09-12
Enrollment: 79
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blind placebo randomized controlled trial
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in flow-mediated dilation (FMD)
timeFrame: Baseline vs 12 weeks post-consumption
Secondary outcomes:
measure: Change in office blood pressure
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in heart rate
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in blood flow velocity
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in pulse wave velocity (PWV)
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in augmentation Index (AIx)
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in blood lipid concentrations
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in blood inflammatory markers (circulating concentrations)
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in 24-hour heart rate
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in 24-hour ambulatory blood pressure
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in 24-hour AIx and PWV
timeFrame: Baseline vs 12 weeks post-consumption
Other outcomes:
measure: Change in urinary metabolic (poly)phenol metabolite concentrations
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in plasmatic metabolic (poly)phenol metabolite concentrations
timeFrame: Baseline vs 12 weeks post-consumption
measure: Gut microbiome composition
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in verbal-episodic memory performance assessed by AVLT
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in executive function performance assessed by the switching task
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in visual-spatial working memory performance assessed by the Corsi task
timeFrame: Baseline vs 12 weeks post-consumption
measure: Change in mood using the PANAS questionnaire
timeFrame: Baseline vs 12 weeks post-consumption
Locations:
city: London
country: United Kingdom
facility: Department of Nutritional Sciences, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London
Study officials:
affiliation: King's College London
name: Ana Rodriguez-Mateos, PhD
role: PRINCIPAL_INVESTIGATOR
References: