Our primary objective is to determine the effect of Salvia miltiorrhiza extract (Danshen) on hyperlipidemia, in particular LDL-cholesterol. Secondary objective is to investigate the effect of Danshen on hypertension. Further objectives are to…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Outcome parameters will be assessed in the 4th week of each treatment period.
To study the effect of Danshen on hyperlipidemia, in particular
LDL-cholesterol, but also HDL-cholesterol, total cholesterol, total
triglycerides, apolipoprotein B plasma levels and LDL oxidation will be
measured.
Secondary outcome
Blood pressure will be quantified by 24-h Ambulatory Blood Pressure Monitoring
and office blood pressure monitoring (during 20 min. period). Endothelial
function will be assessed by both the forearm vasodilator response to infusion
of acetylcholine and nitroprusside into the brachial artery, quantified by
venous occlusion strain gauge plethysmography, and by measuring flow-mediated
dilatation of the brachial artery by ultrasound. Ischemia-reperfusion injury
will be determined by measuring flow-mediated dilatation of the brachial artery
after applying increasing periods of forearm ischemia. Furthermore, plasma
biomarkers of oxidative stress (e.g. TBARS) and vascular inflammation (e.g.
hsCRP) will be sampled. In addition, markers of hemostasis (e.g. von Willebrand
factor), and hemorheological parameters, such as blood viscosity, will be
determined. Insulin sensitivity will be assessed by use of the QUICKI index.
Background summary
Cardiovascular Disease (CVD) is the leading cause of death worldwide. Mortality
due to CVD has declined as a result of both primary (general population without
a history of CVD) and secondary prevention (patients with a history of CVD)
initiatives. The best approach to the problem is the treatment and prevention
of risk factors for CVD. Hypertension and hyperlipidemia belong to the main
risk factors of the development of atherosclerotic cardiovascular disease.
Extracts of the plant Salvia miltiorrhiza (Chinese name *Danshen*) have been
used as traditional Chinese medicine in the treatment of cardiovascular
diseases, such as angina pectoris and myocardial infarction. In China, Danshen
has been extensively studied in clinical trials over the last decades. However,
the methodological quality of these studies was poor, and reliable conclusions
from these studies could not be drawn. Several preclinical studies point
towards promising effects of Danshen on risk factors of atherosclerotic
cardiovascular diseases, such as hyperlipidemia and hypertension. Danshen has
potent antioxidant properties and is shown to have promising effects on
endothelial dysfunction and ischemia-reperfusion injury. Therefore, we want to
investigate the cardiovascular effects of Salvia miltiorrhiza extract (Danshen)
in a well-controlled clinical study.
Study objective
Our primary objective is to determine the effect of Salvia miltiorrhiza extract
(Danshen) on hyperlipidemia, in particular LDL-cholesterol. Secondary objective
is to investigate the effect of Danshen on hypertension. Further objectives are
to determine its effect on endothelial dysfunction and ischemia-reperfusion
injury, and to explore its effect on markers for oxidative stress and vascular
inflammation, and on hemorheological parameters and hemostasis, and on insulin
sensitivity.
Study design
This is a single-centre, placebo-controlled, randomized, double-blind,
cross-over study.
Intervention
The study will consist of two treatment periods of four weeks with a washout
period of four weeks. Total duration 12 weeks. In one treatment period, Danshen
(3 capsules, orally administered twice daily) will be given, in the other
treatment period, a similar dosing schedule with placebo capsules will be used.
Study burden and risks
Salvia miltiorrhiza extract (Danshen) has been used for hundreds of years by
large populations. No serious side effects have been described. The cannulation
of the brachial artery (under local anaesthesia), and the venous blood samples
will give some local discomfort. Both flow-mediated dilatation and
plethysmography will cause temporary and completely reversible numbness and
discomfort in both hands due to inflation of the wrist-cuffs. The subjects may
benefit from participating in this study when Danshen appears to improve
vascular function and risk factors. A subject fee is to be provided.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
* Age: 40-70 (50% men / 50% women)
* Women:
- postmenopausal, or
- use of contraceptive pill
* Hyperlipidemia
- elevated level of triglycerides: > 1.7 mmol/L
- elevated level of LDL-cholesterol: > 3.5 mmol/L
- reduced level of HDL-cholesterol: < 1.03 mmol/L
* Hypertension:
- systolic pressure > 90 mm Hg
- diastolic pressure > 140 mm Hg
* Signed informed consent
Exclusion criteria
* Smoking
* Alcohol or drug abuse
* History of cardiovascular disease (myocard infarct, angina pectoris, CVA, CI)
* Diabetes mellitus
* Pregnancy
* Concomitant (chronic) use of:
- ACE-inhibitors
- Statins
- Anticoagulant drugs
- > 1 antihypertensive drug
- High-dose antihypertensive medication (above defined daily dose)
- (Antioxidant) vitamin supplements
* Clinically significant liver disease (3 times the upper normal limit of ALAT,ASAT,AF, *GT or LDH)
* Clinically significant anemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L)
* Abnormal creatinine clearance (adjusted for age of subject)
* Participation to any drug-investigation during the previous 90 days
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 | NL37508.091.11 |