Physiological Effects of Grape Seed Extract in Diastolic Heart Failure

NCT ID: NCT01185067

Last Updated: 2017-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2014-02-24

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.

Conditions

Diastolic Heart Failure; Hypertensive Heart Disease; Heart Failure With Preserved Ejection Fraction; Hypertension; Oxidative Stress

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

grape seed extract capsule

Grape seed extract (MegaNatural BP, Polyphenolics, Inc.) 300 milligram capsules twice daily for six weeks

Group Type: ACTIVE_COMPARATOR

grape seed extract (MegaNatural BP, Polyphenolics, Inc.)

Intervention Type: DRUG

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.

maltodextrin capsule

Maltodextrin capsules (matched for appearance and taste to grape seed extract capsules) twice daily for six weeks

Group Type: PLACEBO_COMPARATOR

grape seed extract (MegaNatural BP, Polyphenolics, Inc.)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

grapes; wine; polyphenols; resveratrol; quercetin; anthocyanins; flavonoids; flavanols; flavonols; antioxidants

Eligibility 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)

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Scott L. Hummel

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Scott L Hummel, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18948553 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 17513948 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19608210 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19646193 (View on PubMed)

Other Identifiers

HUM00029626

Identifier Type: -

Identifier Source: org_study_id