Primary Objective: The primary objective is to assess the effects of the oral administration of a daily dose of 1000 mg polyphenol extract for 3 weeks on biochemical markers of leucocyte recruitment in patients with documented CAD. Secondary…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint:
Assessment of biochemical markers of leucocyte recruitment in patients with CAD
(MCP-1 (CCL2), CCL5, MIF, SDF-1).
Secondary outcome
Secondary endpoints:
- Flow mediated dilatation (FMD): vasoreactivity of the brachial artery
(measured as % change in diameter) at baseline and 3 weeks
- Laser doppler perfusion imaging (LDPI) and iontophoresis: vasoreactivity of
the cutaneous microvasculature at baseline and 3 weeks
- Assessment of coronary endothelial (dys)function by an endothelial-dependent
vasomotion test with acetylcholine (AC). The number of patients with a
paradoxical vasoconstriction to AC is recorded in each study group.
- Blood sampling at baseline and 3 weeks:
Biochemical markers of inflammation (hs-CRP, IL1ß, IL6, IL10, PIGF,
TNF* and VEGFa).
Monocyte chemokine and adhesion molecule profile (CCL2-5, CCR1-2,
CXCR4, LFA1): flowcytometry
Monocyte/macrophage polarization: cell culture, qPCR)
Background summary
Endothelial dysfunction presents as an early culprit during the initiation and
development of atherosclerosis and is manifest in subsequent stages of
progressive coronary artery disease (CAD). Polyphenol supplementation has been
shown to enhance endothelial function in vitro and reduce the inflammatory
status in animal models of atherosclerosis and in patients at high
cardiovascular risk. However, the direct effects of polyphenol supplementation
on the inflammatory status and the relationship with coronary endothelial
function in patients with CAD have not been elucidated.
Study objective
Primary Objective:
The primary objective is to assess the effects of the oral administration of a
daily dose of 1000 mg polyphenol extract for 3 weeks on biochemical markers of
leucocyte recruitment in patients with documented CAD.
Secondary Objectives:
The secondary objectives are to assess the effects of dietary supplementation
with a daily dose for 3 weeks of 1000 mg polyphenol extract on:
- vasoreactivity of the brachial artery (FMD) and the cutaneous
microvasculature (laser doppler)
- coronary endothelial function during angiography (vasomotion test)
- biochemical markers of inflammation
- monocyte chemokine and adhesion molecule profile (flowcytometry) and
monocyte/macrophage polarization (CAC cell culture, qPCR)
in patients with documented CAD.
Study design
Randomized double-blind placebo-controlled pilot study
Intervention
The intervention group will be treated with a dietary supplement Polyphenols
(Vinitrox), while the other group receives a placebo. In addition to the
dietary supplement/placebo, all patients undergo at 3 weeks a clinically
indicated coronary angiography, including additional invasive measurements
Study burden and risks
The RWPC is believed to restore dysfunctional endothelial function by several
possible mechanisms, e.g. anti-inflammatory action, reducing monocyte
recruitment into atheroslerotic lesions, reducing endothelial cell adhesion of
inflammatory cells, and induce macrophage polarization towards an
anti-inflammatory phenotype. In this way the RWPC will give additional
protection to the study subjects. No serious adverse events are expected from
the oral administration of the compound in its proposed dose.
All subjects undergo invasive evaluation and/or treatment for coronary artery
disease. This investigation generally is not different from the current common
practice in cardiology and supported by the guidelines of the ACC/AHA/ESC. The
only difference is that patients will undergo vasomotion testing of a
non-culprit coronary artery after treatment of the coronary culprit lesion. The
risk attributed to the AC test is minimal.
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
18 years or older
& scheduled for CAG/PCI for stable angina pectoris
& with documentation of an abnormal peripheral FMD-measurement
& with signed informed consent.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded from participation in this study:
Patients with unstable angina, vasospastic angina pectoris, recent myocardial infarction, valvular heart disease, clinical evidence of heart failure, left ventricular hypertrophy, uncontrolled hypertension, peripheral vascular disease, LVEF <50%, and/or significant endocrine, hepatic, renal, or inflammatory disease are excluded.
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 | NL49183.078.14 |