Clinical trial NCT02866448: Impact of isoQUercetin and Aspirin on Platelet Function
Official title: The Impact of Isoquercetin and Aspirin on Platelet Function
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Cardiovascular Disease
Keywords: Cardiovascular disease
Flavonoid
Isoquercetin
Aspirin
Platelet function
Vascular function
Blood pressure
Lead sponsor: University of Reading
Sponsor class: OTHER
Collaborators: name: Biotechnology and Biological Sciences Research Council
name: Quercegen Pharmaceuticals
First posted: 2016-08-15
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: 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: 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)).

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in platelet aggregation
timeFrame: Acute Study: measured at -60 (baseline), 120, 240 and 360min
Secondary outcomes:
measure: Change from baseline in Closure Time (CT), measured with a Platelet Function Analyzer (PFA)
timeFrame: Acute study: measured at -60 (baseline), 120, 240 and 360min
measure: Change from baseline in blood pressure (systolic pressure, diastolic pressure and pulse pressure)
timeFrame: Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min
measure: Change from baseline in arterial stiffness measured by digital volume pulse - stiffness index
timeFrame: Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min
measure: Change from baseline in arterial stiffness measured by digital volume pulse - reflection index
timeFrame: Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min
measure: Change from baseline in total plasma quercetin concentration (micromolar)
timeFrame: Acute study: measured at -60 (baseline), 0, 30, 60, 90, 120, 180, 240, 300 and 360min
measure: Change from baseline in total urine quercetin concentration (micromolar)
timeFrame: Acute study: measured at 0 (baseline),120, 240 and 360min
Other outcomes:
Locations:
city: Reading
country: United Kingdom
facility: University of Reading
state: Berkshire
Study officials:
affiliation: University of Reading
name: Julie A Lovegrove, BSc PhD RNutr
role: PRINCIPAL_INVESTIGATOR
References: