Impact of isoQUercetin and Aspirin on Platelet Function

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of acute isoquercetin supplementation, aspirin, and isoquercetin/aspirin combination on platelet aggregation, blood pressure and vasculat stiffness (eg digital volume pulse), as well as investigating the plasma accumulation and urine excretion profiles of quercetin.

Detailed Description
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Cardiovascular disease (CVD) is the leading cause of death worldwide. In 2012, approximately 17.5 million people worldwide died from CVD, representing 31% of global death. Flavonoids are a class of plant secondary metabolites, functioning in the plant to aid in growth. These compounds are found in diets worldwide, and many cohort studies have demonstrated the protective effect of diets high in flavonoids against CVD events, with some studies showing flavonoid intake inversely associated with CV event risk, CV non-fatal events and all-cause mortality. One consistent issue with quercetin as a dietary flavonoid is the plasma concentrations it is able to reach are not always sufficient to provide a protective effect. Therefore, supplementation or pharmacological intervention with flavonoids may offer a solution. Supplementation with isoquercetin, the 3-O-glucoside of quercetin, offers the potential for much higher plasma concentrations of quercetin and its metabolites than dietary sources can offer, with associated increased inhibitory, anti-platelet effects. It must therefore be addressed whether isoquercetin supplementation can effectively reduce platelet function ex vivo, measured by aggregation and closure time, as well as improve vascular function, measured through blood pressure (BP) and vascular stiffness (eg digital volume pulse (DVP)).

Official Title
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The Impact of Isoquercetin and Aspirin on Platelet Function

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: Vehicle control
* Drug: Isoquercetin
* Drug: Aspirin
* Drug: Isoquercetin plus Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Plasma TAG (triacylglycerol) < 4.0 mmol/l Body mass index (BMI) between 18-35 kg/m2 Total cholesterol (TC): <7 mmol/l Systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg Consume less than 5 portions of fruit/vegetables per day Male Exclusion Criteria: Suffered a myocardial infarction/stroke in the past 12 months Diabetic (diagnosed as fasting blood glucose >7 mmol/l) or suffer from other endocrine disorders Suffering from renal or bowel disease or have a history of cholestatic liver or pancreatitis On drug treatment for hyperlipidaemia, hypertension, inflammation or hypercoagulation History of alcohol abuse Planning or on a weight reducing regime Undertake vigorous exercise more than 3 times a week Taking nutritional supplements (e.g. fish oil, calcium) Taking flavonoid supplements Suffering from hayfever Taking any, or intolerant to, NSAIDS including aspirin On any medication, prescribed or not prescribed (or willing to abstain from these during period of study as well as prior 2 week washout period) Using any recreational drugs Vegan Intolerant/allergic to nuts, wheat, dairy Intolerant/allergic to aspirin On, or have taken antibiotics in the last 2 months Had surgery in the last 3 months Smokers, or have smoked in the last month Using e-cigarettes Anaemic: haemoglobin <12.5 g/dl History of gastric ulcers Female

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Vehicle control<br>Subjects will consume 4 x 250mg cellulose capsules containing 250mg cellulose, 62mg Ascorbic acid (Vitamin C), 5mg Nicotinic acid (Vitamin B3) and 0.25mg Folic Acid 1 x 75mg cellulose pill | Drug: Vehicle control<br>* Described in arm<br>* Other names: Vehicle;|
| Experimental: Isoquercetin<br>Subjects will consume 4 x 250mg isoquercetin capsules containing 250mg isoquercetin, 62mg Ascorbic acid (Vitamin C), 5mg Nicotinic acid (Vitamin B3) and 0.25mg Folic Acid 1 x 75mg cellulose pill | Drug: Isoquercetin<br>* Described in arm<br>* Other names: IsoQ, IsoQblend;|
| Active Comparator: Aspirin<br>Subjects will consume 1 x 75mg dispersible aspirin 4 x 250mg cellulose capsules containing 250mg cellulose, 62mg Ascorbic acid (Vitamin C), 5mg Nicotinic acid (Vitamin B3) and 0.25mg Folic Acid | Drug: Aspirin<br>* Described in arm<br>* Other names: ASA;|
| Experimental: Isoquercetin plus Aspirin<br>Subjects will consume 4 x 250mg isoquercetin capsules containing 250mg isoquercetin, 62mg Ascorbic acid (Vitamin C), 5mg Nicotinic acid (Vitamin B3) and 0.25mg folic acid 1 x 75mg dispersible aspirin | Drug: Isoquercetin plus Aspirin<br>* Described in arm<br>* Other names: IsoQ + ASA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in platelet aggregation |  | Acute Study: measured at -60 (baseline), 120, 240 and 360min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Closure Time (CT), measured with a Platelet Function Analyzer (PFA) |  | Acute study: measured at -60 (baseline), 120, 240 and 360min | 
| Change from baseline in blood pressure (systolic pressure, diastolic pressure and pulse pressure) |  | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min | 
| Change from baseline in arterial stiffness measured by digital volume pulse - stiffness index |  | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min | 
| Change from baseline in arterial stiffness measured by digital volume pulse - reflection index |  | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min | 
| Change from baseline in total plasma quercetin concentration (micromolar) |  | Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min | 
| Change from baseline in total urine quercetin concentration (micromolar) |  | Acute study: measured at 0 (baseline),120, 240 and 360min | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiovascular disease, Flavonoid, Isoquercetin, Aspirin, Platelet function, Vascular function, Blood pressure