Intervention study on the effect of quercetin on biomarkers for cardiovascular syndrome in patients with different apolipoprotein E (ApoE) isoforms

ISRCTN	ISRCTN70547688
DOI	https://doi.org/10.1186/ISRCTN70547688
Protocol serial number	N/A
Sponsor	Max Rubner Institute (Germany)
Funder	German Federal Ministry of Education and Research (Bundesministerium Für Bildung und Forschung [BMBF]) (Germany) (ref: 0313856A)

Submission date: 09/05/2008
Registration date: 19/08/2008
Last edited: 14/06/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Jürgen Schrezenmeir
Scientific

Max Rubner-Institute
Federal Research Institute for Nutrition and Food
Hermann-Weigmann-Str. 1
Kiel
24103
Germany

Phone	+49 (0)431 609 2220
Email	juergen.schrezenmeir@mri.bund.de

Study information

Primary study design	Interventional
Study design	A randomised, double-blind, placebo-controlled, cross-over intervention study
Secondary study design	Randomised controlled trial
Scientific title	Intervention study on the effect of quercetin on biomarkers for cardiovascular syndrome in patients with different apolipoprotein E (ApoE) isoforms
Study acronym	Quercetin1
Study objectives	Quercetin is a flavonoid naturally occurring in all plant foods, mainly in onions, broccoli, green cabbage, apples and in lower concentrations in black tea and red wine. Ingestion of flavonoids was inversely correlated with the incidence of cardiovascular diseases, like atherosclerosis and stroke and risk factors like hypertension. The polyphenol quercetin is a potent antioxidant but may also regulate gene expression and might act through anti-inflammatory effects, e.g. regulation of the expression of cellular adhesion molecules (inter-cellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], E-selectin) and of the secretion of pro-inflammatory cytokines (tumour necrotising factor alpha [TNFa]) and chemokines (monocyte chemoattractant protein-1 [MCP-1]), modulation of enzyme acivities and vascular tonus. Only few human intervention studies with quercetin have been performed so far. In this human trial the effect of quercetin in carriers of the apolipoprotein E (ApoE) type 4 with a high risk for development of atherosclerosis and potentially less protected against oxidative damage due to fewer -SH groups will be studied in comparison to ApoE 3 homozygote. In a cross-over design quercetin and placebo will be applied in random order for eight weeks each, intermitted by a three-week wash-out phase. As dietary fats may change endothelial function, this parameter is tested both in the fasting state and following a fat-rich meal. Metabolic and inflammation parameters will be determined in the fasting and in part postprandial state in blood and urine. Low density lipoprotein (LDL) and chylomicron (CM)/remnants will be isolated and tested for adhesion molecules expression on endothelial cells.
Ethics approval(s)	Ethics approval received from the Ethics Committee of the Medical Faculty of the Christian-Albrechts-University of Kiel (Germany) on the 18th May 2007 (ref: A 120/07).
Health condition(s) or problem(s) studied	Cardiovascular disease
Intervention	Patients are randomised to: 1. Quercetin 150 mg 2. Placebo Patients will receive two capsules of one of the above three times a day during principal meals (breakfast, lunch and dinner) for a total of 6 capsules (150 mg) total dose per day. Patients will receive this for eight weeks for each intervention (verum and placebo), interrupted by a wash-out period of three weeks.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Quercetin
Primary outcome measure(s)	Endothelial function (PAT-Index) after 56 (±2) days supplementation.
Key secondary outcome measure(s)	1. Body mass index (BMI) 2. Waist circumference (WC) 3. Waist to hip ratio (WHR) 4. Blood pressure, pulse Changes in: 5. Fasting and postprandial triglycerides (AUC) 6. Fasting and postprandial insulin (AUC) 7. Fasting and postprandial glucose (AUC) 8. Homeostasis model assessment of insulin resistance (HOMA-IR) (insulin-glucose-product) 9. HOMA B-cell function 10. Metabolic regulatory parameters, namely: cholesteryl ester transfer protein (CETP), glutathione (GSH) 11. Lipids and apolipoproteins, namely total triglycerides and in very low density lipoprotein (VLDL)/triglyceride-rich lipoprotein (TRL), apoliprotein B100, total, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol, free fatty acids, lipoprotein A (LpA) 12. Oxidative modification of lipids and oxidative stress, namely: oxidised LDL, isoprostanes 13. LDL- and CM/remnant-induced adhesion molecule expression on endothelial cells (human umbilical vein endothelial cells [HUVEC]) 14. Inflammatory parameters, namely: C-reactive protein (CRP), soluble VCAM (sVCAM), soluble ICAM (sICAM), soluble E-selectin, interleukin-6 (IL-6), TNFa, MCP-1 15. Gene expression profile in monocytes (fasting monocyte isolation), expression of genes which may affect antioxidative status, metabolism and inflammatory responses (arteriosclerosis) Measurements for the secondary outcome will be made after each intervention period.
Completion date	16/05/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target sample size at registration	50
Total final enrolment	49
Key inclusion criteria	1. Healthy male volunteers 2. Aged 45 - 69 years 3. Member of the Metabolic Intervention Cohort Kiel (MICK) 4. Homozygous for ApoE 3 or ApoE 4, or ApoE 3/4 heterozygous 5. Written informed consent
Key exclusion criteria	1. Participation in a clinical study with a medicament or a medicinal product within the last 30 days or simultaneous participation in another clinical examination 2. Inability to understand and to comply with the study protocol 3. Known metabolic or gastro-intestinal diseases, which affect the absorption, metabolism or excretion of food or food components 4. Condition after surgery of the gastro-intestinal tract, which affect gastro-intestinal motility 5. Haemoglobin less than 12 g/dL 6. Ferritin less than 35 µg/L 7. Latex allergy 8. Diabetes (fasting glucose levels greater than 125 mg/dl after repeated determination) 9. Surgery within the last three months, which still affects the current state of health 10. Deformation of finger tips, which inhibits correct recording of the EndoPAT device (measures a Peripheral Arterial Tone [PAT™] signal for assessment of endothelial dysfunction) 11. Illness of thyroid gland, which has metabolic and/or cardiovascular effect 12. Known hepatitis B, hepatitis C, human immunodeficiency virus (HIV) infection or chronic liver disease 13. Kidney malfunction 14. Psychiatric disorders, epilepsy, risk of suicide 15. Drug or alcohol abuse 16. Intake of nitrate and/or calcium antagonists, which affect the blood pressure 17. Intake of drugs affecting the absorption, metabolism or excretion of food components or the gastro-intestinal motility 18. Intake of hormone preparations, particularly cortisone 19. Eating disorders, anorexia, bulimia, unusual outsider dietary habits 20. Legal incapacity
Date of first enrolment	24/05/2007
Date of final enrolment	16/05/2008

Locations

Countries of recruitment

Germany

Study participating centre

Max Rubner-Institute

Kiel
24103
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/05/2013	14/06/2019	Yes	No

Editorial Notes

14/06/2019: Publication reference and total final enrolment added.