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

• ClinicalTrials.gov Identifier: NCT01185067
• Recruitment Status: Completed
• First Posted: August 19, 2010
• Last Update Posted: June 6, 2017
• Sponsor: University of Michigan
• Information provided by (Responsible Party): Scott L. Hummel, University of Michigan

Study Description

Brief Summary:

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 or disease	Intervention/treatment	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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: GRAPe Seed Extract and Ventriculovascular Investigation in Normal Ejection-Fraction Heart Failure
• Actual Study Start Date: October 2010
• Actual Primary Completion Date: November 4, 2013
• Actual Study Completion Date: February 24, 2014

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Brachial artery flow-mediated dilation (FMD) [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
   Ultrasound measure of conduit artery endothelial function
2. Brachial artery flow-mediated dilation (FMD) [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
   Ultrasound measure of conduit artery endothelial function

Secondary Outcome Measures :

1. 24-hour blood pressure [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
   Mean and diurnal variation
2. EndoPAT arterial endothelial function [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
   Plethysmographic measure of resistance arterial endothelial function
3. Carotid-femoral pulse wave velocity [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
4. Maximal exercise capacity and oxygen consumption [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
5. Resting and post-exercise ventricular systolic and diastolic function [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
   Standard and novel echocardiographic measures including strain/strain rate
6. Urinary 8-isoprostanes [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
   Measure of oxidative stress
7. Heart failure related quality of life [ Time Frame: Pre-six weeks of investigational drug and placebo intervention ]
   Minnesota Living With Heart Failure Questionnaire
8. 24-hour blood pressure [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
   Mean and diurnal variation
9. EndoPAT arterial endothelial function [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
   Plethysmographic measure of resistance arterial endothelial function
10. Carotid-femoral pulse wave velocity [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
11. Maximal exercise capacity and oxygen consumption [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
12. Resting and post-exercise ventricular systolic and diastolic function [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
    Standard and novel echocardiographic measures including strain/strain rate
13. Urinary 8-isoprostanes [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
    Measure of oxidative stress
14. Heart failure related quality of life [ Time Frame: Post-six weeks of investigational drug and placebo intervention ]
    Minnesota Living With Heart Failure Questionnaire

Eligibility Criteria

• Ages Eligible for Study: 50 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

Sponsors and Collaborators

University of Michigan

Investigators

• Principal Investigator: Scott L Hummel, MD, MS; University of Michigan

More Information

Publications:

Seymour EM, Singer AA, Bennink MR, Parikh RV, Kirakosyan A, Kaufman PB, Bolling SF. Chronic intake of a phytochemical-enriched diet reduces cardiac fibrosis and diastolic dysfunction caused by prolonged salt-sensitive hypertension. J Gerontol A Biol Sci Med Sci. 2008 Oct;63(10):1034-42. doi: 10.1093/gerona/63.10.1034.

Ma L, Gao HQ, Li BY, Ma YB, You BA, Zhang FL. Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule expression induced by advanced glycation end products through activation of peroxisome proliferators-activated receptor gamma. J Cardiovasc Pharmacol. 2007 May;49(5):293-8. doi: 10.1097/FJC.0b013e31803c5616.

Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009 Dec;58(12):1743-6. doi: 10.1016/j.metabol.2009.05.030. Epub 2009 Jul 15.

Kar P, Laight D, Rooprai HK, Shaw KM, Cummings M. Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. Diabet Med. 2009 May;26(5):526-31. doi: 10.1111/j.1464-5491.2009.02727.x.

• Responsible Party: Scott L. Hummel, Assistant Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT01185067
• Other Study ID Numbers: HUM00029626
• First Posted: August 19, 2010
• Last Update Posted: June 6, 2017
• Last Verified: June 2017

Keywords provided by Scott L. Hummel, University of Michigan:

Grapes; Hypertension; Endothelial function; Antioxidants; Oxidative stress; 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:

Grape Seed Extract; Hypertension; Heart Failure; Heart Diseases; Heart Failure, Diastolic; Vascular Diseases; Cardiovascular Diseases; Resveratrol; Antioxidants; Quercetin; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Antineoplastic Agents, Phytogenic; Antineoplastic Agents