QUAP: Impact of isoQUercetin and Aspirin on Platelet Function

Sponsor

University of Reading (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02866448

Collaborator

Biotechnology and Biological Sciences Research Council (Other), Quercegen Pharmaceuticals (Industry)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Drug: Vehicle control Drug: Isoquercetin Drug: Aspirin Drug: Isoquercetin plus Aspirin	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

The Impact of Isoquercetin and Aspirin on Platelet Function

Study Start Date :

Aug 1, 2016

Actual Primary Completion Date :

Oct 1, 2016

Actual Study Completion Date :

Oct 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Change from baseline in platelet aggregation [Acute Study: measured at -60 (baseline), 120, 240 and 360min]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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