The objective of this study is to evaluate the effects of resveratrol on apo A-I concentrations in subjects with low serum HDL-cholesterol (HDL-c) concentrations at baseline. Minor objectives are to study the effects of resveratrol in the same…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the change in serum apoA-I concentrations and serum
HDL-C.
Secondary outcome
-flow-mediated dilation
-pulse wave velocity
-glucose- en insulineconcentration
-ApoB
-Total cholesterol
-LDL-C
-Triglycerides
-hdCRP
-IL-6
-sICAM-1
-VCAM-1
-MCP-1
-sE Selectin
- Blood chemistry: phosphorus, sodium, potassium, chloride, calcium,
creatinine, blood urea nitrogen (BUN), protein, albumin, gammaGT,
aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), alkaline
phosphatase (ALP), bilirubin
- Haematology: White cell count, red cell count, platelet count, hemoglobin,
hematocrit, mean cell volume, and mean cell hemoglobin concentration, red cell
distribution
- Blood coagulation: Prothrombin time (PT) and aPT
Background summary
Although much effort has been done to lower LDL-cholesterol concentrations,
there is still a substantial risk for cardiovascular disease (CVD). Another
strategy to lower the risk for CVD is elevating the HDL-cholesterol (HDL-C).
Both in vitro and in vivo studies showed that elevating HDL-C or apolipoprotein
A-I (Apo A-I) levels protect against CVD. However, despite many initiatives, no
new widely applicable intervention strategies with proven efficacy have been
developed.
Epidemiologic studies have shown that a higher polyphenol intake is associated
with a lower risk for CVD. Resveratrol, a polyphenol, could, through several
beneficial mechanisms, exert a positive effect on formation of atherosclerotic
plaques and thus on developing CVD. It has been shown in animals that
resveratrol elevates PPAR-alpha activity. This may lead to elevated apo A-I and
HDL-C levels in the blood. However, these effects are not shown in human
intervention studies.
Study objective
The objective of this study is to evaluate the effects of resveratrol on apo
A-I concentrations in subjects with low serum HDL-cholesterol (HDL-c)
concentrations at baseline. Minor objectives are to study the effects of
resveratrol in the same subjects on (1) endothelial function an arterial
stiffness as measured by flow-mediated dilation (FMD) and pulse wave velocity
(PWV) during the fasting and postprandial phase (2) endothelial function of the
retinal microvasculature during the fasting phase (3) lipid and glucose
metabolism during the fasting and postprandial phase, and (4) biomarkers for
low-grade systemic inflammation (interleukin-6 (IL-6), C-reactive protein
(CRP), and endothelial function (monocyte chemotactic protein-1 (MCP-1),
sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble
vascular cell adhesion molecule-1 (sVCAM-1)).
Study design
A randomized, double-blind, placebo controlled cross-over design. The total
study duration will be 12 weeks, consisting of a 4 weeks experimental period, 4
weeks wash-out, and a weeks control period.
Intervention
During the experimental period, subjects will receive one capsule at lunch and
one at dinner daily. Each capsule will provide 75 mg resveratrol. During the
control period, subjects will receive two placebo capsules daily, each
containing 58 mg cellulose.
Study burden and risks
Before the start of the study, subjects will be screened to determine
elegibility during two visits of respectively 15 and 10 minutes. During these
visits, body weight, height and blood pressure will be measured. In addition, a
blood sample (5.5 mL at each occasion) is drawn by venapunction. During the
study, all subjects will receive the control and resveratrol capsules in random
order. At days 1 and 25 of each 4 wk experimental period, a fasting blood
sample will be drawn (2 x 34.5 mL, 2 x 24.5 mL). In addition, a 4hr
postprandial test will be performed at day 28 of each experimental period. For
this, subjects will receive two muffins and 300 mL low-fat milk, and 8 blood
samples will be taken (in total 91 mL). Thus, in total 311 mL blood will be
drawn. During each postprandial test, two FMD and two PWV measurements will be
performed. Both measurements will be performed before and after the
postprandial test. After each 4 wk intervention period a retinal image will be
taken. Before this image is taken, the retina will be widened by tropicamide.
Therefore, it is not allowed to drive a car for up to 3 hours afterwards.
Furthermore, subjects will be asked to fill out a food frequency questionnaire
two times and to keep a study-diary throughout 12 weeks. On rare occasions,
blood sampling might cause bruises or hematoma. Total time investment for each
subject will be approximately 16 hours.
Universiteitsingel 50
6229 ER, Maastricht
NL
Universiteitsingel 50
6229 ER, Maastricht
NL
Listed location countries
Age
Inclusion criteria
• aged between 45 and 70 years
• HDL-C <1.21 mmol/L (men)
• HDL-C <1.53 mmol/L (women)
• serum total cholesterol <8.0 mmol/L
• plasma glucose <7.0 mmol/L
• BMI between 25 - 35 kg/m2
• non-smoking
• willingness to abstain from resveratrol rich products from two weeks prior to the study and the duration of the study:
o grapes
o wine (red and white)
o all berries
o peanuts
o peanut butter
o soy (products)
o pomegranate
Exclusion criteria
• unstable body weight (weight gain or loss >3 kg in the past 3 months)
• indication for treatment with cholesterol-lowering drugs according to the Dutch Cholesterol Consensus
• use of medication or a medically-prescribed diet known to affect serum lipid or glucose metabolism. Oral anti-contraceptives and paracetamol are allowed.
• Active cardiovascular disease (for instance congestive heart failure) or recent (<6 months) event, such as acute myocardial infarction or cerebro-vascular accident
• not willing to stop the consumption of vitamin supplements, fish oil capsules or products rich in plant stanol or sterol esters 3 weeks before the start of the study
• men: consumption of >21 glasses of alcohol-containing drinks per week
women: consumption of >14 glasses of alcohol-containing drinks per week
• abuse of drugs
• pregnant or breastfeeding women
• participation in another biomedical study within 1 month prior to the screening visit
• having donated blood (as blood donor) within 1 month prior to the screening visit or planning to do so during the study
• impossible or difficult to puncture as evidenced during the screening visits
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL32793.068.10 |