Physiological Effects of Grape Seed Extract in Diastolic Heart Failure (GRAPEVINE-HF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Michigan
Sponsor:
Information provided by (Responsible Party):
Scott L. Hummel, University of Michigan
ClinicalTrials.gov Identifier:
NCT01185067
First received: August 2, 2010
Last updated: December 9, 2013
Last verified: December 2013
  Purpose

Diastolic heart failure (also known as "heart failure with normal ejection fraction" or "heart failure with preserved ejection fraction") occurs even though the heart muscle's pumping function is normal. In many cases diastolic heart failure is related to stiffening of the heart and blood vessels in people who have high blood pressure. Current guidelines suggest that patients should limit the salt content of their diet, as too much salty food can cause fluid retention and other problems in diastolic heart failure. Studies in animals with diastolic heart failure suggest that antioxidant chemicals found in grapes can block some of the harmful effects of salty diets. Because it is often difficult for patients with diastolic heart failure to maintain a low salt diet, the investigators are researching the effects of the antioxidant properties of grape seed extract, a natural supplement made from grape seeds. The investigators hypothesize that supplementing the diet with grape seed extract (GSE) can decrease the levels of harmful chemicals and improve heart and blood vessel function in patients with diastolic heart failure and a history of high blood pressure.

The University of Michigan research group plans to enroll 25 patients with a history of high blood pressure and diastolic heart failure in a research study. The study will assess the effects of GSE on hormones and other chemicals that can cause heart and blood vessel damage. The investigators will also study the effects of GSE on the ability of the blood vessels and heart muscles to relax at the proper time and speed. Finally, the investigators will observe how GSE affects participants' overall ability to exercise, quality of life, and blood pressure control. Study participants will be randomly assigned to take either GSE or placebo (looks like but does not contain GSE) capsules twice a day for six weeks. After a two-week break, all subjects will cross over to the opposite group of capsules for an additional six-week period. At the start of the study and at the end of each six-week time period study participants will have non-invasive heart and blood vessel testing, blood work and urine tests, and blood pressure monitoring.


Condition Intervention Phase
Diastolic Heart Failure
Hypertensive Heart Disease
Heart Failure With Preserved Ejection Fraction
Hypertension
Oxidative Stress
Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: GRAPe Seed Extract and Ventriculovascular Investigation in Normal Ejection-Fraction Heart Failure

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Primary Outcome Measures:
  • Brachial artery flow-mediated dilation (FMD) [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Ultrasound measure of conduit artery endothelial function

  • Brachial artery flow-mediated dilation (FMD) [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Ultrasound measure of conduit artery endothelial function


Secondary Outcome Measures:
  • 24-hour blood pressure [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Mean and diurnal variation

  • EndoPAT arterial endothelial function [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Plethysmographic measure of resistance arterial endothelial function

  • Carotid-femoral pulse wave velocity [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
  • Maximal exercise capacity and oxygen consumption [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
  • Resting and post-exercise ventricular systolic and diastolic function [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Standard and novel echocardiographic measures including strain/strain rate

  • Urinary 8-isoprostanes [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Measure of oxidative stress

  • Heart failure related quality of life [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Minnesota Living With Heart Failure Questionnaire

  • 24-hour blood pressure [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Mean and diurnal variation

  • EndoPAT arterial endothelial function [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Plethysmographic measure of resistance arterial endothelial function

  • Carotid-femoral pulse wave velocity [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
  • Maximal exercise capacity and oxygen consumption [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
  • Resting and post-exercise ventricular systolic and diastolic function [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Standard and novel echocardiographic measures including strain/strain rate

  • Urinary 8-isoprostanes [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Measure of oxidative stress

  • Heart failure related quality of life [ Time Frame: Post-six weeks of investigational drug and placebo intervention ] [ Designated as safety issue: No ]
    Minnesota Living With Heart Failure Questionnaire


Estimated Enrollment: 25
Study Start Date: August 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: grape seed extract capsule
Grape seed extract (MegaNatural BP, Polyphenolics, Inc.) 300 milligram capsules twice daily for six weeks
Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
Subjects will be randomized in double-blind fashion to either grape seed extract (GSE) or maltodextrin placebo capsules for for 6 weeks. Patient will take 300 mg GSE/placebo twice a day for 6 weeks. Patient will have a 2 week washout period and then cross over to the opposite group for an additional 6 weeks.
Other Names:
  • grapes
  • wine
  • polyphenols
  • resveratrol
  • quercetin
  • anthocyanins
  • flavonoids
  • flavanols
  • flavonols
  • antioxidants
Placebo Comparator: maltodextrin capsule
Maltodextrin capsules (matched for appearance and taste to grape seed extract capsules) twice daily for six weeks
Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
Subjects will be randomized in double-blind fashion to either grape seed extract (GSE) or maltodextrin placebo capsules for for 6 weeks. Patient will take 300 mg GSE/placebo twice a day for 6 weeks. Patient will have a 2 week washout period and then cross over to the opposite group for an additional 6 weeks.
Other Names:
  • grapes
  • wine
  • polyphenols
  • resveratrol
  • quercetin
  • anthocyanins
  • flavonoids
  • flavanols
  • flavonols
  • antioxidants

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion:

  • Signs and symptoms of heart failure
  • Left ventricular ejection fraction ≥ 50% (contrast ventriculography, echocardiography, nuclear scintigraphy, MRI or CT imaging)
  • Diastolic dysfunction on previous echocardiogram/catheterization, or indeterminate diastolic function with supporting evidence of heart failure (HF) (as per European Society of Cardiology guidelines)
  • History of systemic hypertension
  • Age ≥ 50 years
  • Willing to adhere to prescribed course of supplementation
  • Informed consent

Exclusion Criteria:

  • Daily intake of antioxidant supplements or vitamins beyond that provided in a standard daily multivitamin (e.g. high-dose vitamin E or vitamin C)
  • NYHA Class IV heart failure symptoms (except during previous hospitalization)
  • Hospitalization for decompensated heart failure within past one month
  • Severely uncontrolled hypertension (SBP ≥ 180 and.or DBP ≥ 100 at rest, on current antihypertensive regimen
  • Uncontrolled diabetes mellitus (hemoglobin A1C > 9%)
  • Severe renal (estimated GFR < 30 ml/min) or hepatic disease/failure
  • Severe anemia (Hgb < 9)
  • Primary exercise limitation due to severe pulmonary disease
  • Unacceptably poor echocardiographic images for analysis
  • Worse than moderate mitral or aortic stenosis or insufficiency.
  • Non-hypertensive cause of HFpEF (e.g. valvular disease, congenital heart disease, amyloidosis, sarcoidosis, constrictive pericardial syndromes)
  • Myocardial infarction or unstable angina, including new or worsening anginal syndrome, within the past three months
  • Uncontrolled arrhythmia (including non rate-controlled atrial fibrillation)
  • Terminal illness expected to result in death within six months or active solid-organ cancer
  • Psychiatric disorder (or dementia) with potential to compromise adherence
  • Changes in medical regimen for heart disease or hypertension within past 1 month (except diuretic dose adjustment)
  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: NCT01185067

Contacts
Contact: Joanna Wells 734-232-6383 joannamw@umich.edu

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Scott L Hummel, MD MS    734-936-5265    scothumm@med.umich.edu   
Contact: Joanna M Wells    734 232 6383    joannamw@umich.edu   
Principal Investigator: Scott L Hummel, MD MS         
Sponsors and Collaborators
University of Michigan
Investigators
Principal Investigator: Scott L Hummel, MD, MS University of Michigan
  More Information

Publications:
Responsible Party: Scott L. Hummel, Assistant Professor, University of Michigan
ClinicalTrials.gov Identifier: NCT01185067     History of Changes
Other Study ID Numbers: HUM00029626
Study First Received: August 2, 2010
Last Updated: December 9, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Michigan:
Antioxidants
Hypertension
Endothelial function
Oxidative stress
Grapes
Polyphenols
Resveratrol
Quercetin
Anthocyanins
Flavanols
Flavonols
Congestive heart failure
Heart failure with normal ejection fraction
Heart failure with preserved systolic function
HFNEF
HFPSF
HFPEF
DHF

Additional relevant MeSH terms:
Antioxidants
Heart Diseases
Heart Failure
Hypertension
Heart Failure, Diastolic
Cardiovascular Diseases
Vascular Diseases
Quercetin
Resveratrol
Grape Seed Extract
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Hematologic Agents
Antimutagenic Agents
Anticarcinogenic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 31, 2014