Impact of isoQUercetin and Aspirin on Platelet Function (QUAP)

The Impact of Isoquercetin and Aspirin on Platelet Function

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.

Study Overview

• Status: Withdrawn
• Conditions: Cardiovascular Disease
• Intervention / Treatment: Drug: Vehicle control; Drug: Isoquercetin; Drug: Aspirin; Drug: Isoquercetin plus Aspirin

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)).

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Berkshire
    • Reading, Berkshire, United Kingdom, RG6 6AP
      • University of Reading

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Vehicle control; 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; Described in arm; Other Names: Vehicle
Experimental: Isoquercetin; 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; Described in arm; Other Names: IsoQ, IsoQblend
Active Comparator: Aspirin; 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; Described in arm; Other Names: ASA
Experimental: Isoquercetin plus Aspirin; 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; Described in arm; Other Names: IsoQ + ASA

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Reading
• Collaborators: Biotechnology and Biological Sciences Research Council; Quercegen Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: August 2, 2016
• First Submitted That Met QC Criteria: August 10, 2016
• First Posted (Estimate): August 15, 2016

Study Record Updates

• Last Update Posted (Estimate): November 29, 2016
• Last Update Submitted That Met QC Criteria: November 28, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Aspirin; Cardiovascular disease; Blood pressure; Platelet function; Vascular function; Flavonoid; Isoquercetin
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 16/38

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will be averaged (some will also be normalized) before publishing, IPD (Individual Participant Data) will not be made available