Resveratrol-enriched Grape Extract (Stilvid) in Primary and Secondary Prevention of Cardiovascular Disease (FUNGRAPE)

A Randomized, 12 Months Follow-up, Dose-response, Placebo-Controlled, Double-Blind, 6-Arms Parallel Trial to Evaluate the Safety and Efficacy of a Resveratrol-enriched Grape Extract (Stilvid) in Primary and Secondary Patients of Cardiovascular Disease

Resveratrol can exhibit benefits against cardiovascular diseases (CVDs) although the cardioprotective role of resveratrol as part of the human diet is not yet clear.

The aim of this trial is to evaluate the safety and efficacy of a resveratrol-enriched grape extract (Stilvid) in 150 patients from both primary and secondary cardiovascular prevention.

All the patients are gold-standard medicated (statins and others). A number of cardiovascular risk and safety markers will be evaluated after consuming 1 cap/day for 6 months and 2 caps/day for 6 additional months (total 12 months).

Study Overview

• Status: Completed
• Conditions: Cardiovascular Diseases
• Intervention / Treatment: Dietary supplement: Placebo in primary cardiovascular prevention (PP); Dietary supplement: Placebo in secondary prevention; Dietary supplement: Grape extract in primary prevention (PP); Dietary supplement: Grape extract in SP; Dietary supplement: Resveratrol-enriched grape extract in PP; Dietary supplement: Resveratrol-enriched grape extract in SP

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Murcia, Spain, 30008
    • University Hospital Morales Meseguer

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

FOR PRIMARY PREVENTION:

• Lack of known cardiovascular disease (coronary acute syndrome, stable ischemic cardiopathy, peripheric arteriopathy and cerebrovascular diseases).
• Age between 18 and 80 years.

• The above criteria and diabetes mellitus or at least two of the following risk factors:

  1. Active smoking (10 cigarettes or more per day).
  2. Arterial hypertension (>= 140/90 mmHg).
  3. Hypercholesterolemia (LDL-cholesterol >130 mg/dL and/or HDL-cholesterol < 45 mg/dL in women and 50 mg/dL in men).
  4. Obesity (BMI > 30 kg/m2)

FOR SECONDARY PREVENTION:

• Stable patients who coronary syndrome, cerebrovascular accident or peripheric arteriopathy event occurred at least 6 months or more before the recruitment in the study. In addition:

  1. Age between 18 and 80 years.
  2. Ejection fraction of left ventricle >=45%.
  3. Functional status I or II according to the New York Heart Association.
  4. Clinic stability in the recruitment (no symptoms of thoracic pain during the last month).

  5. Lack of residual lesions without vascularization in those patients with catheterism.

     Exclusion Criteria:

     FOR PRIMARY AND SECONDARY PREVENTION:

• Patients who do not satisfy inclusion criteria and:

  1. Known allergy to grapes
  2. Pregnancy or lactation
  3. Intake of nutraceuticals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo in PP; Placebo arm in primary cardiovascular prevention (PP)	Dietary supplement: Placebo in primary cardiovascular prevention (PP); 12 months follow-up: capsule/day of placebo (350 mg maltodextrin) for 6 months; capsules/day of placebo (350 mg + 350 mg maltodextrin) for 6 months; Other Names: Group A-PP
Placebo Comparator: Placebo in SP; Placebo arm in secondary cardiovascular prevention (SP)	Dietary supplement: Placebo in secondary prevention; 12 months follow-up: capsule/day (350 mg maltodextrin) for 6 months; capsules/day (350 mg + 350 mg maltodextrin) for 6 months; Other Names: Group A-SP
Active Comparator: Grape extract in PP; Grape extract obtained without resveratrol in primary cardiovascular prevention	Dietary supplement: Grape extract in primary prevention (PP); 12 months follow-up: capsule/day (350 mg grape extract) for 6 months; capsules/day (350 mg + 350 mg grape extract) for 6 months; Other Names: Group B-PP
Active Comparator: Grape extract in SP; Grape extract without resveratrol in secondary cardiovascular prevention	Dietary supplement: Grape extract in SP; 12 months follow-up: capsule/day (350 mg grape extract) for 6 months; capsules/day (350 mg + 350 mg grape extract) for 6 months; Other Names: Group B-SP
Experimental: Resveratrol-enriched grape extract in PP; Resveratrol-enriched grape extract (Stilvid) in primary cardiovascular prevention	Dietary supplement: Resveratrol-enriched grape extract in PP; Resveratrol-enriched grape extract (Stilvid) is obtained from grapes treated with UVC illumination. Similar polyphenolic content to conventional grape extract used in the arms 'Grape extract in PP' and 'Grape extract in SP' but containing 8 mg resveratrol. 12 months follow-up: capsule/day (350 mg resveratrol-enriched grape extract) for 6 months; capsules/day (350 mg + 350 mg resveratrol-enriched grape extract) for 6 months; Other Names: Group C-PP; Stilvid is the key ingredient of Revidox (Actafarma, Spain)
Experimental: Resveratrol-enriched grape extract in SP; Resveratrol-enriched grape extract (Stilvid) in secondary cardiovascular prevention	Dietary supplement: Resveratrol-enriched grape extract in SP; Resveratrol-enriched grape extract (Stilvid) is obtained from grapes treated with UVC illumination. Similar polyphenolic content to conventional grape extract used in the arms 'Grape extract in PP' and 'Grape extract in SP' but containing 8 mg resveratrol. 12 months follow-up: capsule/day (350 mg resveratrol-enriched grape extract) for 6 months; capsules/day (350 mg + 350 mg resveratrol-enriched grape extract) for 6 months; Other Names: Stilvid is the key ingredient of Revidox (Actafarma, Spain); Group C-SP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Apolipoprotein-B	6 months
oxidized LDL particles	6 months
Plasminogen activator inhibitor type 1 (PAI-1)	6 months and 12 months
Adiponectin	6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C Reactive Protein		6 months 12 months
Interleukin-6		6 months and 12 months
Interleukin-10		6 months and 12 months
Interleukin-18		6 months and 12 months
sICAM-1		6 months and 12 months
sVCAM-1		6 months and 12 months
D-dimer		6 months and 12 months
Fibrinogen		6 months and 12 months
Glycated hemoglobin		6 months and 12 months
Glucose		6 months and 12 months
GGT		6 months and 12 months
AST		6 months and 12 months
Urate		6 months and 12 months
ALT		6 months and 12 months
LDH		6 months and 12 months
TSH		6 months and 12 months
Thyroxine		6 months and 12 months
ALP		6 months and 12 months
CPK		6 months and 12 months
Bilirubin		6 months and 12 months
Creatinin		6 months and 12 months
Albumin		6 months and 12 months
Total cholesterol		6 months and 12 months
LDL-cholesterol		6 months and 12 months
HDL-cholesterol		6 months and 12 months
Triglycerides		6 months and 12 months
Hematocrit		6 months and 12 months
Hemoglobin		6 months and 12 months
Mean corpuscular volume		6 months and 12 months
Leucocytes		6 months and 12 months
Neutrophils		6 months and 12 months
Lymphocytes		6 months and 12 months
Eosinophils		6 months and 12 months
Platelets		6 months and 12 months
Mean platelet volume		6 months and 12 months
Sedimentation rate volume		6 months and 12 months
Gene expression profile in peripheral blood mononuclear cells (PBMNCs)	Transcriptomic study. Evaluation of the gene expression profile in PBMNCs in a diabetic sub-group from Secondary prevention.	6 months and 12 months
Total homocystein levels	Total homocystein levels in plasma evaluated with UPLC-MS-QqQ	6 months and 12 months
Measurement of atheroma plaque and carotid intim thickness		12 months

Collaborators and Investigators

• Sponsor: National Research Council, Spain
• Collaborators: Hospital General Universitario Morales Meseguer
• Investigators: Principal Investigator: Juan Carlos Espín, PhD, National Research Council (CEBAS-CSIC, Murcia, Spain)

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (Estimate): October 7, 2011

Study Record Updates

• Last Update Posted (Estimate): November 16, 2011
• Last Update Submitted That Met QC Criteria: November 15, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: Cardiovascular; Secondary prevention; Primary prevention; Resveratrol; Nutraceutical; Grape; Food complement
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Antioxidants; Resveratrol
• Other Study ID Numbers: CEBAS-CSIC-1