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

This study has been terminated.
(Not able to recruit qualified patents)
Sponsor:
Collaborator:
Horphag Research
Information provided by (Responsible Party):
Ronald Watson, University of Arizona
ClinicalTrials.gov Identifier:
NCT00952627
First received: August 3, 2009
Last updated: December 14, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Cardiac Fibrosis
Diastolic Dysfunction
Dietary Supplement: Pycnogenol
Dietary Supplement: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • liver and kidney function tests [ Time Frame: at baseline and at 4 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: July 2009
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pycnogenol
200 mg/day
Dietary Supplement: Pycnogenol
50 mg tablet, 200 mg/day, 4 tablets/day
Placebo Comparator: Control
placebo
Dietary Supplement: Placebo

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

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00952627

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

Additional Information:
No publications provided

Responsible Party: Ronald Watson, Prinicpal Investigator, University of Arizona
ClinicalTrials.gov Identifier: NCT00952627     History of Changes
Other Study ID Numbers: UofAFRS 439130
Study First Received: August 3, 2009
Last Updated: December 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Arizona:
Cardiac fibrosis
Diastolic dysfunction
Hypertension

Additional relevant MeSH terms:
Fibrosis
Pathologic Processes
Pycnogenols
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 21, 2014