Diastolic Heart FailurePhase 1GRAPEVINE-HFNCT01185067
Physiological Effects of Grape Seed Extract in Diastolic Heart Failure
A Phase 1 study testing grape seed extract (MegaNatural BP, Polyphenolics, Inc.) in people with Diastolic Heart Failure and Hypertensive Heart Disease, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Diastolic Heart Failure, Hypertensive Heart Disease, Heart Failure With Preserved Ejection Fraction
- What is being tested?
- grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to 24 Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: GRAPe Seed Extract and Ventriculovascular Investigation in Normal Ejection-Fraction Heart Failure
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
- Being tested
- grape seed extract (MegaNatural BP, Polyphenolics, Inc.)
- 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
- Medical subject headings
- Heart Failure, Diastolic, Hypertension, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
grape seed extract (MegaNatural BP, Polyphenolics, Inc.)Drug
Also called grapes, wine, polyphenols, resveratrol
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.
| Study group | Role | What they receive |
|---|---|---|
| grape seed extract capsule | Active comparator | Grape seed extract (MegaNatural BP, Polyphenolics, Inc.) 300 milligram capsules twice daily for six weeks Receives: Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.) |
| maltodextrin capsule | Placebo comparator | Maltodextrin capsules (matched for appearance and taste to grape seed extract capsules) twice daily for six weeks Receives: Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial artery flow-mediated dilation (FMD)
Ultrasound measure of conduit artery endothelial function
Measured: Pre-six weeks of investigational drug and placebo intervention
Brachial artery flow-mediated dilation (FMD)
Ultrasound measure of conduit artery endothelial function
Measured: Post-six weeks of investigational drug and placebo intervention
Secondary outcomes (14)
24-hour blood pressure
Mean and diurnal variation
Measured: Pre-six weeks of investigational drug and placebo intervention
EndoPAT arterial endothelial function
Plethysmographic measure of resistance arterial endothelial function
Measured: Pre-six weeks of investigational drug and placebo intervention
Carotid-femoral pulse wave velocity
Measured: Pre-six weeks of investigational drug and placebo intervention
Maximal exercise capacity and oxygen consumption
Measured: Pre-six weeks of investigational drug and placebo intervention
Resting and post-exercise ventricular systolic and diastolic function
Standard and novel echocardiographic measures including strain/strain rate
Measured: Pre-six weeks of investigational drug and placebo intervention
Urinary 8-isoprostanes
Measure of oxidative stress
Measured: Pre-six weeks of investigational drug and placebo intervention
Heart failure related quality of life
Minnesota Living With Heart Failure Questionnaire
Measured: Pre-six weeks of investigational drug and placebo intervention
24-hour blood pressure
Mean and diurnal variation
Measured: Post-six weeks of investigational drug and placebo intervention
EndoPAT arterial endothelial function
Plethysmographic measure of resistance arterial endothelial function
Measured: Post-six weeks of investigational drug and placebo intervention
Carotid-femoral pulse wave velocity
Measured: Post-six weeks of investigational drug and placebo intervention
Maximal exercise capacity and oxygen consumption
Measured: Post-six weeks of investigational drug and placebo intervention
Resting and post-exercise ventricular systolic and diastolic function
Standard and novel echocardiographic measures including strain/strain rate
Measured: Post-six weeks of investigational drug and placebo intervention
Urinary 8-isoprostanes
Measure of oxidative stress
Measured: Post-six weeks of investigational drug and placebo intervention
Heart failure related quality of life
Minnesota Living With Heart Failure Questionnaire
Measured: Post-six weeks of investigational drug and placebo intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2010 (estimated)
- Study startOct 2010
- Primary completion4 Nov 2013
- Study completion24 Feb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Diastolic Heart FailureStudies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Scott L. Hummel, University of Michigan
- Investigators
- Scott L Hummel, MD, MS, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01185067
- Sponsor's protocol ID
- HUM00029626
- Acronym
- GRAPEVINE-HF
- Status last verified
- Jun 2017
- First submitted
- 2 Aug 2010
- Last updated
- 6 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 18948553Ma 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.
PubMed 17513948Sivaprakasapillai 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.
PubMed 19608210Kar 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.
PubMed 19646193
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRAPe Seed Extract and Ventriculovascular Investigation in Normal Ejection-Fraction Heart Failure
- ClinicalTrials.gov ID
- NCT01185067
- Acronym / sponsor ID
- GRAPEVINE-HF / HUM00029626
- Conditions
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Study start
- Oct 2010 (actual)
- Primary completion
- 4 Nov 2013 (actual)
- Study completion
- 24 Feb 2014 (actual)
- First posted
- 19 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| grape seed extract capsule | Active comparator | Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.)Grape seed extract (MegaNatural BP, Polyphenolics, Inc.) 300 milligram capsules twice daily for six weeks |
| maltodextrin capsule | Placebo comparator | Drug: grape seed extract (MegaNatural BP, Polyphenolics, Inc.)Maltodextrin capsules (matched for appearance and taste to grape seed extract capsules) twice daily for six weeks |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (16 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| grape seed extract (MegaNatural BP, Polyphenolics, Inc.)Also: grapes, wine, polyphenols, resveratrolSubjects 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. | Drug | grape seed extract capsule, maltodextrin capsule |
Primary outcome
Brachial artery flow-mediated dilation (FMD)
Time frame: Pre-six weeks of investigational drug and placebo intervention
Ultrasound measure of conduit artery endothelial function
Brachial artery flow-mediated dilation (FMD)
Time frame: Post-six weeks of investigational drug and placebo intervention
Ultrasound measure of conduit artery endothelial function
14 secondary outcomes
24-hour blood pressure
Time frame: Pre-six weeks of investigational drug and placebo intervention
EndoPAT arterial endothelial function
Time frame: Pre-six weeks of investigational drug and placebo intervention
Carotid-femoral pulse wave velocity
Time frame: Pre-six weeks of investigational drug and placebo intervention
Maximal exercise capacity and oxygen consumption
Time frame: Pre-six weeks of investigational drug and placebo intervention
Resting and post-exercise ventricular systolic and diastolic function
Time frame: Pre-six weeks of investigational drug and placebo intervention
Urinary 8-isoprostanes
Time frame: Pre-six weeks of investigational drug and placebo intervention
Heart failure related quality of life
Time frame: Pre-six weeks of investigational drug and placebo intervention
24-hour blood pressure
Time frame: Post-six weeks of investigational drug and placebo intervention
EndoPAT arterial endothelial function
Time frame: Post-six weeks of investigational drug and placebo intervention
Carotid-femoral pulse wave velocity
Time frame: Post-six weeks of investigational drug and placebo intervention
Maximal exercise capacity and oxygen consumption
Time frame: Post-six weeks of investigational drug and placebo intervention
Resting and post-exercise ventricular systolic and diastolic function
Time frame: Post-six weeks of investigational drug and placebo intervention
Urinary 8-isoprostanes
Time frame: Post-six weeks of investigational drug and placebo intervention
Heart failure related quality of life
Time frame: Post-six weeks of investigational drug and placebo intervention
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2017.
- Background: PubMed 18948553Seymour 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.
- Background: PubMed 17513948Ma 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.
- Background: PubMed 19608210Sivaprakasapillai 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.
- Background: PubMed 19646193Kar 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott L Hummel, MD, MS principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing grape seed extract (MegaNatural BP, Polyphenolics, Inc.) in people with Diastolic Heart Failure and Hypertensive Heart Disease, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brachial artery flow-mediated dilation (FMD) (time frame: Pre-six weeks of investigational drug and placebo intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01185067, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2017.