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

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Active smoking (10 cigarettes or more per day). Arterial hypertension (>= 140/90 mmHg). Hypercholesterolemia (LDL-cholesterol >130 mg/dL and/or HDL-cholesterol < 45 mg/dL in women and 50 mg/dL in men). 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: Age between 18 and 80 years. Ejection fraction of left ventricle >=45%. Functional status I or II according to the New York Heart Association. Clinic stability in the recruitment (no symptoms of thoracic pain during the last month). 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: Known allergy to grapes Pregnancy or lactation Intake of nutraceuticals

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo in PP<br>Placebo arm in primary cardiovascular prevention (PP) | Dietary Supplement: Placebo in primary cardiovascular prevention (PP)<br>* 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<br>* Other names: Group A-PP;|
| Placebo Comparator: Placebo in SP<br>Placebo arm in secondary cardiovascular prevention (SP) | Dietary Supplement: Placebo in secondary prevention<br>* 12 months follow-up: capsule/day (350 mg maltodextrin) for 6 months capsules/day (350 mg + 350 mg maltodextrin) for 6 months<br>* Other names: Group A-SP;|
| Active Comparator: Grape extract in PP<br>Grape extract obtained without resveratrol in primary cardiovascular prevention | Dietary Supplement: Grape extract in primary prevention (PP)<br>* 12 months follow-up: capsule/day (350 mg grape extract) for 6 months capsules/day (350 mg + 350 mg grape extract) for 6 months<br>* Other names: Group B-PP;|
| Active Comparator: Grape extract in SP<br>Grape extract without resveratrol in secondary cardiovascular prevention | Dietary Supplement: Grape extract in SP<br>* 12 months follow-up: capsule/day (350 mg grape extract) for 6 months capsules/day (350 mg + 350 mg grape extract) for 6 months<br>* Other names: Group B-SP;|
| Experimental: Resveratrol-enriched grape extract in PP<br>Resveratrol-enriched grape extract (Stilvid) in primary cardiovascular prevention | Dietary Supplement: Resveratrol-enriched grape extract in PP<br>* 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<br>* Other names: Stilvid is the key ingredient of Revidox (Actafarma, Spain);|
| Experimental: Resveratrol-enriched grape extract in SP<br>Resveratrol-enriched grape extract (Stilvid) in secondary cardiovascular prevention | Dietary Supplement: Resveratrol-enriched grape extract in SP<br>* 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<br>* Other names: Stilvid is the key ingredient of Revidox (Actafarma, Spain);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Primary prevention, Secondary prevention, Resveratrol, Grape, Cardiovascular, Nutraceutical, Food complement