Back to resultsPhysiological Effects of Grape Seed Extract in Diastolic Heart Failure (GRAPEVINE-HF)
Primary Purpose
Diastolic Heart Failure, Hypertensive Heart Disease, Heart Failure With Preserved Ejection Fraction
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
Sponsored by
About this trial
This is an interventional treatment trial for Diastolic Heart Failure focused on measuring Hypertension, Endothelial function, Antioxidants, 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
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)
Sites / Locations
- University of Michigan
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
grape seed extract capsule
maltodextrin capsule
Arm Description
Grape seed extract (MegaNatural BP, Polyphenolics, Inc.) 300 milligram capsules twice daily for six weeks
Maltodextrin capsules (matched for appearance and taste to grape seed extract capsules) twice daily for six weeks
Outcomes
Primary Outcome Measures
Brachial artery flow-mediated dilation (FMD)
Ultrasound measure of conduit artery endothelial function
Brachial artery flow-mediated dilation (FMD)
Ultrasound measure of conduit artery endothelial function
Secondary Outcome Measures
24-hour blood pressure
Mean and diurnal variation
EndoPAT arterial endothelial function
Plethysmographic measure of resistance arterial endothelial function
Carotid-femoral pulse wave velocity
Maximal exercise capacity and oxygen consumption
Resting and post-exercise ventricular systolic and diastolic function
Standard and novel echocardiographic measures including strain/strain rate
Urinary 8-isoprostanes
Measure of oxidative stress
Heart failure related quality of life
Minnesota Living With Heart Failure Questionnaire
24-hour blood pressure
Mean and diurnal variation
EndoPAT arterial endothelial function
Plethysmographic measure of resistance arterial endothelial function
Carotid-femoral pulse wave velocity
Maximal exercise capacity and oxygen consumption
Resting and post-exercise ventricular systolic and diastolic function
Standard and novel echocardiographic measures including strain/strain rate
Urinary 8-isoprostanes
Measure of oxidative stress
Heart failure related quality of life
Minnesota Living With Heart Failure Questionnaire
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01185067
Brief Title
Physiological Effects of Grape Seed Extract in Diastolic Heart Failure
Acronym
GRAPEVINE-HF
Official Title
GRAPe Seed Extract and Ventriculovascular Investigation in Normal Ejection-Fraction Heart Failure
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 2010 (Actual)
Primary Completion Date
November 4, 2013 (Actual)
Study Completion Date
February 24, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Michigan
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diastolic Heart Failure, Hypertensive Heart Disease, Heart Failure With Preserved Ejection Fraction, Hypertension, Oxidative Stress
Keywords
Hypertension, Endothelial function, Antioxidants, 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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
grape seed extract capsule
Arm Type
Active Comparator
Arm Description
Grape seed extract (MegaNatural BP, Polyphenolics, Inc.) 300 milligram capsules twice daily for six weeks
Arm Title
maltodextrin capsule
Arm Type
Placebo Comparator
Arm Description
Maltodextrin capsules (matched for appearance and taste to grape seed extract capsules) twice daily for six weeks
Intervention Type
Drug
Intervention Name(s)
grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
Other Intervention Name(s)
grapes, wine, polyphenols, resveratrol, quercetin, anthocyanins, flavonoids, flavanols, flavonols, antioxidants
Intervention Description
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.
Primary Outcome Measure Information:
Title
Brachial artery flow-mediated dilation (FMD)
Description
Ultrasound measure of conduit artery endothelial function
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
Brachial artery flow-mediated dilation (FMD)
Description
Ultrasound measure of conduit artery endothelial function
Time Frame
Post-six weeks of investigational drug and placebo intervention
Secondary Outcome Measure Information:
Title
24-hour blood pressure
Description
Mean and diurnal variation
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
EndoPAT arterial endothelial function
Description
Plethysmographic measure of resistance arterial endothelial function
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
Carotid-femoral pulse wave velocity
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
Maximal exercise capacity and oxygen consumption
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
Resting and post-exercise ventricular systolic and diastolic function
Description
Standard and novel echocardiographic measures including strain/strain rate
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
Urinary 8-isoprostanes
Description
Measure of oxidative stress
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
Heart failure related quality of life
Description
Minnesota Living With Heart Failure Questionnaire
Time Frame
Pre-six weeks of investigational drug and placebo intervention
Title
24-hour blood pressure
Description
Mean and diurnal variation
Time Frame
Post-six weeks of investigational drug and placebo intervention
Title
EndoPAT arterial endothelial function
Description
Plethysmographic measure of resistance arterial endothelial function
Time Frame
Post-six weeks of investigational drug and placebo intervention
Title
Carotid-femoral pulse wave velocity
Time Frame
Post-six weeks of investigational drug and placebo intervention
Title
Maximal exercise capacity and oxygen consumption
Time Frame
Post-six weeks of investigational drug and placebo intervention
Title
Resting and post-exercise ventricular systolic and diastolic function
Description
Standard and novel echocardiographic measures including strain/strain rate
Time Frame
Post-six weeks of investigational drug and placebo intervention
Title
Urinary 8-isoprostanes
Description
Measure of oxidative stress
Time Frame
Post-six weeks of investigational drug and placebo intervention
Title
Heart failure related quality of life
Description
Minnesota Living With Heart Failure Questionnaire
Time Frame
Post-six weeks of investigational drug and placebo intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott L Hummel, MD, MS
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
18948553
Citation
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.
Results Reference
background
PubMed Identifier
17513948
Citation
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.
Results Reference
background
PubMed Identifier
19608210
Citation
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.
Results Reference
background
PubMed Identifier
19646193
Citation
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.
Results Reference
background
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Physiological Effects of Grape Seed Extract in Diastolic Heart Failure
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