Effects of Pycnogenol on Cardiac Fibrosis and Diastolic Dysfunction in Aged Hypertensive Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00952627
Recruitment Status : Terminated (Not able to recruit qualified patents)
First Posted : August 6, 2009
Last Update Posted : December 17, 2013
Horphag Research
Information provided by (Responsible Party):
Ronald Watson, University of Arizona

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.

Condition or disease Intervention/treatment Phase
Cardiac Fibrosis Diastolic Dysfunction Dietary Supplement: Pycnogenol Dietary Supplement: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : July 2009
Actual Primary Completion Date : July 2011
Actual Study Completion Date : July 2011

Arm Intervention/treatment
Experimental: Pycnogenol
200 mg/day
Dietary Supplement: Pycnogenol
50 mg tablet, 200 mg/day, 4 tablets/day

Placebo Comparator: Control
Dietary Supplement: Placebo

Primary Outcome Measures :
  1. cardiac fibrosis (by measuring the serum markers of myocardial fibrosis and collagen turnover) and diastolic dysfunction (by transthoracic echocardiogram) [ Time Frame: at baseline and at 4 months ]

Secondary Outcome Measures :
  1. liver and kidney function tests [ Time Frame: at baseline and at 4 months ]
  2. Immunological measurements including the cytokine profile in serum (interleukin (IL)-4, IL-10, interferon-gamma, C-reactive protein). [ Time Frame: baseline and at 4 months ]

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Ages Eligible for Study:   50 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00952627

United States, Arizona
University of Arizona, Sarver Heart Center
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
University of Arizona
Horphag Research
Principal Investigator: Ronald R Watson, PhD University of Arizona

Responsible Party: Ronald Watson, Prinicpal Investigator, University of Arizona Identifier: NCT00952627     History of Changes
Other Study ID Numbers: UofAFRS 439130
First Posted: August 6, 2009    Key Record Dates
Last Update Posted: December 17, 2013
Last Verified: December 2013

Keywords provided by Ronald Watson, University of Arizona:
Cardiac fibrosis
Diastolic dysfunction

Additional relevant MeSH terms:
Pathologic Processes
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Platelet Aggregation Inhibitors