Cardiovascular-Protective Effects of Herbal Medicine Danshen-Gegen

A Novel Randomized Double-Blind Placebo-Control Clinical Trial in High-Risk Hypertensive Subjects

Atherosclerosis (in particular stroke and heart attack) is the most important health issue in modernized society and high blood pressure is an important predisposing factor. Hypertensive subjects with other chronic disease such as diabetes mellitus or impaired renal function are particularly vulnerable to these atherosclerotic complications in spite of standard antihypertensive therapies.

Danshen and Gegen are commonly used in Chinese materia medica as treatment for cardiac symptoms and atherosclerosis-related disorders.

The objective of this study is to test Danshen and Gegen as an cardiovascular-protective adjunctive regimen to prevent high-risk hypertensive cohort from primary atherosclerosis.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Placebo; Drug: D&G 1g; Drug: D&G 2g

Detailed Description

Danshen and Gegen (D&G) are two traditional herbal medicines used for cardiac symptoms in ancient Chinese medicinal literature. Recent studies suggest their therapeutic effects in blood pressure and lipid-lowering, anti-oxidation, microcirculation-promoting, foam cells-modulation and have beneficial effects on atherogenic process in coronary patients.

To evaluate the potential of D&G in primary atherosclerosis prevention in high risk hypertension. Patients with high risk hypertension associated with left ventricular hypertrophy, diabetes mellitus and renal insufficiency were randomized to receive D&G herbal capsules (2gm/day), or (1gm/day) or identical placebo capsules in double-blind and parallel fashion for 12 months on top of their anti-hypertensive treatments. Flow-mediated dilation (endothelium-dependent dilation, FMD) and nitroglycerin-induced dilation (endothelium-independent dilation, NTG) of brachial artery, and carotid intima-media thickness (surrogate atherosclerosis marker, IMT) were measured by high resolution B-mode ultrasound.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong
    • Alice Ho Miu Ling Nethersole Hospital
  • Hong Kong, Hong Kong
    • Yan Chai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• High-risk hypertension: Asymptomatic hypertensive (pretreatment BP>160/95mmHg) subjects, currently blood pressure under control (BP<140/90mmHg),
• Aged 35-70 years
• With either (i)left ventricular hypertrophy on ECG or echocardiographic criteria, (ii) diabetes mellitus, or (iii) mild renal impairment (plasma creatinine 120-250µmol/l)

Exclusion Criteria:

• Known intolerance to D&G due to adverse effect, patients with bleeding, disorders or on long-term anticoagulation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Image-matched placebo of active treatment	Drug: Placebo; Image-matched placebo, made with starch.
Active Comparator: D&G 1g; Randomly allocated into three groups, D&G capsule 1g/day	Drug: D&G 1g; Danshen consists of the dried root and rhizome of the perennial herb Salvia miltiorrhiza Bge. Gegen is the dried roots of Pueraria lobata (willd.). The combination in the ratio of 7:3 of the raw herbs. Capsule form, Orally taken 1g per Day; Other Names: Danshen Gegen
Active Comparator: D&G 2g; Randomly allocated into three groups, D&G capsule 2g/day	Drug: D&G 2g; Danshen consists of the dried root and rhizome of the perennial herb Salvia miltiorrhiza Bge. Gegen is the dried roots of Pueraria lobata (willd.). The combination in the ratio of 7:3 of the raw herbs. Capsule form, Orally taken 2g per Day; Other Names: Danshen Gegen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ultrasound study for measuring carotid intima-media thickening (IMT)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood tests: lipids, creatinine, glucose, fibrinogen, hs-CRP and haemoglobin A1-C Physical examination: Blood pressure, weight, height, body mass index, hip waist ratio	1 year

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Thomas YK Chan, Prof., Department of Medicine & Therapeutics, Prince of Wales Hospital

Publications and helpful links

General Publications

• Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997 Sep 2;96(5):1432-7. doi: 10.1161/01.cir.96.5.1432.
• O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med. 1999 Jan 7;340(1):14-22. doi: 10.1056/NEJM199901073400103.
• Woo KS, Chook P, Raitakari OT, McQuillan B, Feng JZ, Celermajer DS. Westernization of Chinese adults and increased subclinical atherosclerosis. Arterioscler Thromb Vasc Biol. 1999 Oct;19(10):2487-93. doi: 10.1161/01.atv.19.10.2487.
• Sieveking DP, Woo KS, Fung KP, Lundman P, Nakhla S, Celermajer DS. Chinese herbs Danshen and Gegen modulate key early atherogenic events in vitro. Int J Cardiol. 2005 Oct 20;105(1):40-5. doi: 10.1016/j.ijcard.2004.10.052.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: December 15, 2009
• First Submitted That Met QC Criteria: December 15, 2009
• First Posted (Estimate): December 16, 2009

Study Record Updates

• Last Update Posted (Estimate): December 16, 2009
• Last Update Submitted That Met QC Criteria: December 15, 2009
• Last Verified: January 1, 2006

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: CRE2005123T