Cardiovascular Effects of Salvia Miltiorrhiza Extract (Danshen)

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

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.

Study Overview

• Status: Unknown
• Conditions: Inflammation; Hypertension; Dyslipidemias; Oxidative Stress; Vasodilation
• Intervention / Treatment: Dietary supplement: Salvia miltiorrhiza extract; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands, 6500 HB
    • Recruiting
    • Radboud University Nijmegen Medical Centre
    • Contact: Pauline Breedveld, PhD; Phone Number: +31-243614597; Email: p.breedveld@pharmtox.umcn.nl
    • Contact: Pleun van Poppel, MD; Phone Number: +31-243667211; Email: p.vanpoppel@aig.umcn.nl
    • Principal Investigator: Gerard Rongen, MD, PhD, Professor
    • Sub-Investigator: Cees J. Tack, MD, PhD, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Salvia miltiorrhiza extract (Danshen); p.o. Salvia miltiorrhiza extract, 1.5 g twice daily for four consecutive weeks	Dietary supplement: Salvia miltiorrhiza extract; 3 capsules of 500 mg Salvia miltiorrhiza extract, twice daily for four consecutive weeks; Other Names: Danshen
Placebo Comparator: placebo; p.o. placebo, twice daily	Dietary supplement: Placebo; 3 placebo capsules, twice daily for four consecutive weeks

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Gerard Rongen, MD, PhD, Professor, Radboud University Medical Center

Publications and helpful links

General Publications

• van Poppel PC, Breedveld P, Abbink EJ, Roelofs H, van Heerde W, Smits P, Lin W, Tan AH, Russel FG, Donders R, Tack CJ, Rongen GA. Salvia Miltiorrhiza Root Water-Extract (Danshen) Has No Beneficial Effect on Cardiovascular Risk Factors. A Randomized Double-Blind Cross-Over Trial. PLoS One. 2015 Jul 20;10(7):e0128695. doi: 10.1371/journal.pone.0128695. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): March 1, 2013

Study Registration Dates

• First Submitted: March 23, 2012
• First Submitted That Met QC Criteria: March 26, 2012
• First Posted (Estimate): March 27, 2012

Study Record Updates

• Last Update Posted (Estimate): May 24, 2012
• Last Update Submitted That Met QC Criteria: May 23, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Keywords: Oxidative stress; Inflammation; Hypertension; Hemostasis; Vasodilation; Hyperlipidemia; Cardiovascular diseases; Hemorheology; Therapeutic Uses; Molecular Mechanisms of Pharmacological Action; Cardiovascular agents; Salvia miltiorrhiza; Danshen; Danshen root extract
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hypertension; Inflammation; Dyslipidemias
• Other Study ID Numbers: QPHT-35