Condition category
Circulatory System
Date applied
09/05/2008
Date assigned
19/08/2008
Last edited
19/08/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.mri.bund.de

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

Publication citations

Additional files

Editorial Notes