Contact information
Type
Scientific
Primary contact
Prof Jürgen Schrezenmeir
ORCID ID
Contact details
Max Rubner-Institute
Federal Research Institute for Nutrition and Food
Hermann-Weigmann-Str. 1
Kiel
24103
Germany
+49 (0)431 609 2220
juergen.schrezenmeir@mri.bund.de
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Quercetin1
Study hypothesis
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
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).
Study design
A randomised, double-blind, placebo-controlled, cross-over intervention study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
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 names
Quercetin
Primary outcome measures
Endothelial function (PAT-Index) after 56 (±2) days supplementation.
Secondary outcome measures
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.
Overall trial start date
24/05/2007
Overall trial end date
16/05/2008
Reason abandoned
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Male
Target number of participants
50 (apoE 3/3 [n = 20], apoE 4/4 [n = 10], apoE 3/4 [n = 20])
Participant 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
Recruitment start date
24/05/2007
Recruitment end date
16/05/2008
Locations
Countries of recruitment
Germany
Trial participating centre
Max Rubner-Institute
Kiel
24103
Germany
Sponsor information
Organisation
Max Rubner Institute (Germany)
Sponsor details
c/o Prof. Jürgen Schrezenmeir
Federal Research Institute of Nutrition and Food
Haid-und-Neu-Str. 9
Karlsruhe
76131
Germany
pbe.kiel@mri.bund.de
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
German Federal Ministry of Education and Research (Bundesministerium Für Bildung und Forschung [BMBF]) (Germany) (ref: 0313856A)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary