Cardiovascular Effects of Salvia Miltiorrhiza Extract (Danshen)

Study Overview
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Brief Summary
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Rationale: Extracts of the plant Salvia miltiorrhiza (Danshen) have been used as traditional Chinese medicine in the treatment of cardiovascular diseases, such as angina pectoris and myocardial infarction. Several preclinical studies point towards promising effects of Danshen on risk factors of atherosclerotic cardiovascular diseases, such as hyperlipidemia and hypertension. Objective: Our primary objective is to determine the effect of Salvia miltiorrhiza extract (Danshen) on hyperlipidemia. Secondary objective is to investigate the effect of Danshen on hypertension. Further objectives are to determine its effect on endothelial function, oxidative stress, inflammation, hemostasis and hemorheology, and on insulin sensitivity.

Official Title
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A Double Blind, Randomized Placebo-controlled Cross-over Study on the Cardiovascular Effects of Salvia Miltiorrhiza Extract (Danshen) in Patients With Hypertension and Hyperlipidemia.

Conditions
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Dyslipidemias, Hypertension, Vasodilation, Oxidative Stress, Inflammation

Intervention / Treatment
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* Dietary Supplement: Salvia miltiorrhiza extract
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 40-70 Women: postmenopausal, or use of contraceptive pill Hyperlipidemia: elevated level of triglycerides: > 1.7 mmol/L, or elevated level of LDL-cholesterol: > 3.5 mmol/L Hypertension: systolic pressure > 140 mm Hg, or diastolic pressure > 90 mm Hg Signed informed consent Exclusion Criteria: Alcohol or drug abuse History of cardiovascular disease (myocard infarct, angina pectoris, CVA) Diabetes mellitus, when treated with insulin Pregnancy Hyperlipidemia which needs conventional treatment elevated level of triglycerides: > 8 mmol/L elevated level of LDL-cholesterol: > 5 mmol/L Hypertension which needs conventional treatment: systolic pressure > 180 mm Hg diastolic pressure > 110 mm Hg Clinically significant liver disease (3 times the upper normal limit of ALAT,ASAT) Clinically significant anemia (male Hb < 6,9 mmol/L, female < 6,25 mmol/L) Renal disease defined as MDRD < 60 ml/min/1.73m2 Participation to any drug-investigation during the previous 90 days Use of any herbal product during the previous 30 days Concomitant (chronic) use of: Medicinal products: ACE-inhibitors, including a.o. captopril, enalapril, ramipril AT1-antagonists, including a.o. losartan, valsartan, irbesartan Statins, including a.o. simvastatin, rosuvastatin Anticoagulant drugs, including a.o. aspirin Calciumantagonists (including a.o. amlodipine, nifedipine, verapamil) Use of more than 1 antihypertensive drug High-dose antihypertensive medication (above defined daily dose) Drugs which are exclusively metabolised by CYP3A4 (Flockhart DA; P450 drug interaction table, including a.o. erythromycin, midazolam, cyclosporine, HIV antivirals) Food products: (Antioxidant) vitamin supplements Other herbs, including a.o. St John's wort Grapefruit juice

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salvia miltiorrhiza extract (Danshen)<br>p.o. Salvia miltiorrhiza extract, 1.5 g twice daily for four consecutive weeks | Dietary Supplement: Salvia miltiorrhiza extract<br>* 3 capsules of 500 mg Salvia miltiorrhiza extract, twice daily for four consecutive weeks<br>* Other names: Danshen;|
| Placebo Comparator: placebo<br>p.o. placebo, twice daily | Dietary Supplement: Placebo<br>* 3 placebo capsules, twice daily for four consecutive weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hyperlipidemia | Blood tests: lipids, in particular LDL-cholesterol. | after 4 weeks of treatment with Danshen | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hypertension |  | after 4 weeks of treatment with Danshen | 
| Endothelial function |  | after 4 weeks of treatment with Danshen | 
| Plasma markers of oxidative stress |  | after 4 weeks of treatment with Danshen | 
| Vascular inflammation and inflammatory activation of adipose tissue |  | after 4 weeks of treatment with danshen | 
| Hemostasis and hemorheological parameters |  | after 4 weeks of treatment with Danshen | 
| Insulin sensitivity |  | after 4 weeks of treatment with Danshen | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperlipidemia, Hypertension, Vasodilation, Oxidative stress, Inflammation, Hemostasis, Hemorheology, Cardiovascular diseases, Cardiovascular agents, Salvia miltiorrhiza, Danshen, Danshen root extract, Molecular Mechanisms of Pharmacological Action, Therapeutic Uses