Study Effects of Ginkgo Biloba Extract on Endothelial Cell Function and Genetic Effects on the Response to Ginkgo Biloba Extract in Diabetic Patients With Stable Coronary Artery Disease

This study is enrolling participants by invitation only.
Sponsor:
Information provided by:
Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov Identifier:
NCT01038050
First received: December 20, 2009
Last updated: December 22, 2009
Last verified: December 2009
  Purpose

Type 2 diabetes is associated with a markedly increased risk for atherosclerotic coronary arteries and cerebrovascular diseases. The major cause of death in diabetic patients is cardiovascular disease in the world including Taiwan. Atherosclerosis is a progressive disease characterized by the response of the vessel wall to chronic, multifactorial injury, which leads ultimately to the formation of atheromatous or fibrous plaques. Endothelial dysfunction is thought to be the initial stage of atherosclerosis. Endothelial dysfunction leads to impaired control of vascular tone, a decreased in the release of anti-inflammatory factors and reduced availability of nitric oxide. Endothelial dysfunction portends diabetic vasculopathy. The loss of intact endothelial integrity and function sets in motion a cascade of serial events that lead to atherosclerosis and cardiovascular complications.

The standard extracts of G. biloba leaves [G. biloba extract (GBE)] are now demonstrated the cardiovascular, cerebrovascular and neuroprotective effects. The mixture of biologically active ingredients in GBE accounts for the pleiotropic effects, including antioxidant effects, inhibition of platelet aggregation and thromboxane B2 production, vasodilation and modulation of cholesterol metabolism. Clinically, GBE was widely used in management of vertigo、dementia and improving peripheral circulation. In our previous study, ginkgo biloba extract inhibits tumor necrosis factor-alpha-induced reactive oxygen species generation, transcription factor activation, and cell adhesion molecule expression in human aortic endothelial cells. In addition, the similar benefit of prevention atherosclerosis was also found in animal study.

Heme oxygenase-1 (HO-1) is a factor associated with higher risk of developing some vascular disease and also a rate-limiting enzyme in heme degradation, leading to the generation of free iron, biliverdin, and carbon monoxide (CO). CO exerts potent antiproliferative and anti-inflammatory effects in the vascular walls, thereby influencing neointimal formation after vascular injury. In addition, biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Therefore, induction of HO-1 elicits potent anti-inflammatory, antiproliferative, antithrombotic, and antioxidant effects in the circulation via the generation of CO and bilirubin. Interestingly, recent study found that a long guanidine thymidine dinucleotide repeat [(GT) n≧ 30] in the HO-1 promotor, which is linked to impaired inducibility, is associated with a higher frequency of vascular access failure.

In the present study, we will investigate the effect of GBE on recovering endothelial dysfunction and inflammation in diabetic patients with stable coronary artery disease. In particularly, we intend to determine whether the GBE modulates the HO-1 expression and investigate whose genotyping including some candidate gene about atherosclerosis and hypertension will have most therapeutic effect of GBE.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Coronary Artery Disease
Drug: Ginkgo Biloba Extract (GBE)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Taipei Veterans General Hospital, Taiwan:

Primary Outcome Measures:
  • Number of endothelial progenitor cells, endothelial function(FMD) [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Ginkgo Biloba Extract (GBE)
    Ginkgo Biloba Extract 40 mg 1# tid per day for 3 months(90 days)
    Other Name: Cerenin(Ginkgo Biloba Extract) film-coated 40 mg
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Thirty type 2 diabetes mellitus with stable coronary disease
  • Aged 18-80 year-old

Exclusion Criteria:

  • Previous underwent coronary artery bypass surgery or percutaneous angioplasty
  • Under insulin injection patients
  • Renal or hepatic function impairment
  • Pregnant women
  • Poor BP control(BP>175/105 mmHg)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01038050

Locations
Taiwan
Taipei Veterans General Hospital
Taipei, Taiwan, 11217
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
Investigators
Principal Investigator: Jaw-Wen Chen, MD Division of Cardiology, Taipei Veterans General Hospital
Principal Investigator: Chin-Chou Huang, MD Division of Cardiology, Taipei Veterans General Hospital
  More Information

No publications provided

Responsible Party: Liang-Yu, Lin/ Attending phsician, Taipei Veterans General Hospital
ClinicalTrials.gov Identifier: NCT01038050     History of Changes
Other Study ID Numbers: VGHIRB 98-10-02
Study First Received: December 20, 2009
Last Updated: December 22, 2009
Health Authority: Taiwan: Institutional Review Board

Keywords provided by Taipei Veterans General Hospital, Taiwan:
Endothelial progenitor cell
endothelial function(FMD)
Gingko Biloba Extract
Type 2 Diabetes mellitus
Stable coronary artery disease
Endothelial progenitor cells Numbers

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Diabetes Mellitus
Diabetes Mellitus, Type 2
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Heart Diseases
Metabolic Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on October 23, 2014