Clinical trial NCT00952627: Effects of Pycnogenol on Cardiac Fibrosis and Diastolic Dysfunction in Aged Hypertensive Subjects
Official title: Mechanism of the Anti-remodeling Activity of the Over-the-counter Dietary Supplement, Pycnogenol, on Age-dependent Process of Cardiac Fibrosis in Aged Hypertensive Subjects With Echocardiographic Evidence of Grade I/II Diastolic Dysfunction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cardiac Fibrosis
Diastolic Dysfunction
Keywords: Cardiac fibrosis
Diastolic dysfunction
Hypertension
Lead sponsor: University of Arizona
Sponsor class: OTHER
Collaborators: name: Horphag Research
First posted: 2009-08-06
Enrollment: 9
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether Pycnogenol, a natural pine bark extract, is effective in modifying the age-dependent process of cardiac fibrosis and diastolic function in aged hypertensive subjects.

Detailed description: Diastolic heart failure without left ventricular systolic dysfunction comprises 30% to 50% of heart failure in clinical practice, and hypertensive heart disease is a major cause of this type of heart failure. The complication of myocardial fibrosis should be avoided in hypertensive heart disease, because increasing ventricular stiffness caused by myocardial fibrosis leads to the development of diastolic dysfunction of the heart. Diastolic dysfunction in patients with prolonged hypertension is often associated with myocardial fibrosis in addition to muscular hypertrophy as a final feature of hypertensive heart disease. The high risk of developing maladaptive cardiac remodeling during hypertension, and failure of pharmacological treatments to limit or even reverse this progressive stiffening of the myocardium, has led to the study of effects of Pycnogenol, a bioflavonoid-rich pine bark extract, with pleiotropic actions on cardiovascular system. Pycnogenol prevents adverse hypertension-induced myocardial remodeling in mice, through modulation of gene expression and activity of enzyme matrix metalloproteinases and their tissue inhibitors, affecting myocardial collagen degradation rate. Despite the mounting evidence suggesting the anti-remodeling effect of Pycnogenol in animal models, the clinical efficacy of Pycnogenol in hypertension-induced diastolic dysfunction is unreported. This leads to our central hypothesis that Pycnogenol reverses the hypertension-induced cardiac fibrosis and diastolic dysfunction in hypertensive patients. Therefore in this clinical investigation, we will investigate the effects of Pycnogenol in modifying hypertension-induced cardiac fibrosis (by measuring the serum markers of myocardial fibrosis and collagen turnover) and diastolic dysfunction (by transthoracic echocardiogram). We expect to improve diastolic function and ameliorate myocardial fibrosis with the nutritional supplement Pycnogenol, by modulation of MMPs and TIMPs enzyme activities.

Eligibility criteria: Inclusion Criteria:

* The subjects will consist of ambulatory males and females, 50-75 years of age, of any race, diagnosed with hypertension (diagnosis made over 6 months), and echocardiographic evidence of grade I or II diastolic dysfunction.
* There is no need for standardization of hypertension treatment, as we select only patients who have diastolic dysfunction during treatment.

Exclusion Criteria:

* Unstable angina or myocardial infarction in the past 3 months.
* Biochemical evidence of renal or hepatic failure.
* Severe anemia: defined as hemoglobin level less than 7 g/dL.
* Current cancer or other major illness not associated with the heart.
* Bleeding disorders.
* Taking anticoagulants including low dose aspirin.
* Diabetes.
* Known allergy to Pycnogenol.
* Being pregnant or breastfeeding.
* Systolic blood pressure over 180 mmHg or less than 100 mmHg, and Diastolic blood pressure over 110 mmHg or less than 50 mmHg.
* Current smoking.
* Having breast implants.
* Taking any of the following: birth control products, Diethylstilbestrol, Ephedra, ephedrine, or pseudoephedrine (except where used in prescription products), hormone replacement products, Isotretinoin, any product containing mercury, Phentermine in combination with fenfluramine (including but not limited to Pondimin) or dexfenfluramine (Redux).

Primary outcomes:
measure: cardiac fibrosis (by measuring the serum markers of myocardial fibrosis and collagen turnover) and diastolic dysfunction (by transthoracic echocardiogram)
timeFrame: at baseline and at 4 months
Secondary outcomes:
measure: liver and kidney function tests
timeFrame: at baseline and at 4 months
measure: Immunological measurements including the cytokine profile in serum (interleukin (IL)-4, IL-10, interferon-gamma, C-reactive protein).
timeFrame: baseline and at 4 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona, Sarver Heart Center
state: Arizona
Study officials:
affiliation: University of Arizona
name: Ronald R Watson, PhD
role: PRINCIPAL_INVESTIGATOR
References: