Pycnogenol and Endothelial Function in Coronary Artery Disease

Study Overview
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Brief Summary
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Pycnogenol® is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica). Pycnogenol® has prevented pathologic symptoms such as chronic inflammation and increased platelet aggregation, a risk factor for cardiovascular diseases. The endothelium is increasingly recognized not only a target (with vascular remodelling occurring in response to an injury and resulting in atherosclerosis), but also a mediator in the pathogenesis of atherosclerosis. Indeed, endothelial cells play an important regulatory role in the cardiovascular system by the expression of numerous molecules and release of mediators such as nitric oxide (NO), superoxide and endothelin-1 (ET-1). Data from animal studies, as well as human studies indicate that Pycnogenol may improve endothelial function, which is a powerful surrogate for clinical prognosis.

Official Title
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A Double-blind, Randomized, Placebo-controlled, Cross - Over Design, Single Center Study to Evaluate the Effects of Treatment With Pycnogenol® on Endothelial Function in Subjects With Stable Coronary Artery Disease (Pycno2007-003)

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Drug: Pycnogenol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of coronary artery disease (documented by coronary angiogram, nuclear imaging, positive stress test) Stable cardiovascular medication for at least 1 month Age ≥ 18 years of age at time of signing the informed consent Informed consent for participation in the study Exclusion Criteria: Myocardial infarction, unstable angina, stroke (within 3 months before randomization) Thoracic or cardiac surgery and/or coronary intervention/revascularisation procedure (within 3 months before randomization) Uncontrolled symptomatic congestive heart failure (NHYA> II) in the last 4 weeks prior to study Renal insufficiency (Creatinine Clearance < 50ml/min) Ventricular tachyarrhythmias Poorly controlled hypertension, defined as resting blood pressure ≥ 160/100 mmHg Symptomatic hypotension Obstructive cardiomyopathy, active myocarditis, constrictive pericarditis, untreated hypothyroidism or hyperthyroidism and adrenal insufficiency Severe uncorrected valvular disease or left ventricular outflow obstruction, which, in the opinion of the investigator, requires surgery Long acting nitrates Oral or intravenous steroids therapy Insulin - dependent diabetes mellitus Recipient of any major organ transplant (eg, lung, liver, heart) or renal replacement therapy Malignancy (unless healed or remission > 5 years) Anaemia (Hb< 10g/dl) Known to be human immunodeficiency virus (HIV) positive or active virus - hepatitis Alanine transaminase (ALT) or aspartate transaminase (AST) > 3 times the upper limit of the normal range Known hypersensitivity to Pycnogenol® Alcohol, nicotine abuse or illicit drug abuse Pregnancy or breast-feeding, women with child - bearing potential without adequate contraception Disease with systemic inflammation (e.g. rheumatoid arthritis, M. Crohn) Participation in another study within the last month

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo 100mg twice daily<br>|
| Active Comparator: Pycnogenol<br> | Drug: Pycnogenol<br>* Pycnogenol 100mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this study is to evaluate the effects of treatment with Pycnogenol® on endothelial function in subjects with stable coronary artery disease. |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary objectives are to evaluate the effect of 8 weeks treatment with Pycnogenol® on inflammation markers, oxidative stress parameters, endothelial progenitor cells, platelet function, 24 hours blood pressure and baroreflex function. |  | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Disease, endothelial dysfunction, Nitric oxide