Supplementation of Lycopene in Carotid Atheroma

Study Overview
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Brief Summary
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Stroke is the second leading cause of death worldwide. One of the causes of stroke which can be treated is narrowing of the carotid artery. Currently the only definite treatment option is surgery or endovascular treatment. All patients not qualified for or awaiting surgery are, therefore, left with best medical therapy and with a yearly risk of stroke anywhere between 1% - 35% depending on the severity of the disease. The study will use the properties of a tomato extract containing lycopene. Previously studies have demonstrated beneficial properties of tomato extracts: It decreases lipid oxidation It decreases DNA damage It has properties that reduce the speed and amount of cell divisions that inflammatory and smooth muscle cells undergo (both of these cell types contribute to atheroma formation). The investigators wish to assess whether long-term food supplementation with a tomato extract containing lycopene could influence atherosclerotic plaque characteristics. The investigators will assess this using Magnetic Resonance Imaging of the plaque and transcranial Doppler ultrasonography for counting the number of blood clots that go to the brain's arteries. Furthermore the investigators wish to examine the effect of long-term food supplementation with a tomato extract containing lycopene on blood cholesterol levels and lipid oxidation and blood markers of inflammation and injury of the inner lining of the arteries. This will be a single center, double blind, randomised, placebo controlled study.

Official Title
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Supplementation of Lycopene on Carotid Atheroma: Neovascularisation and Morphology (SOLANUM) Study

Conditions
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Carotid Atherosclerotic Disease

Intervention / Treatment
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* Drug: Placebo
* Dietary Supplement: Ateronon


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 40 - 90 years old, Clinically documented carotid symptomatic atherosclerotic disease (symptomatic disease will be considered if one of the following has occurred within 2 months prior to symptoms: Amaurosis fugax Transient ischemic attack (TIA) Stroke (ipsilaterally to the stenotic artery) >30% stenosis on initial B-mode ultrasonography imaging, Written, informed consent. Exclusion Criteria: Age <40 years old or >90 years old, Time from symptom to recruitment > 2 months <30% stenosis on B-mode ultrasonography imaging, Scheduled for surgical/endovascular intervention within 3 months, High-dose statin therapy (>80 mg/day fluvastatin; >40 mg/day simvastatin; >40 mg/day pravastatin; >10 mg/day atorvastatin; >10 mg/day rosuvastatin 21), Other lipid-lowering therapy (fibric acid derivatives, niacin ≥250 mg/day, resins, ezetimibe, fish-oil supplements), Chronic use of high dose aspirin >325 mg/day, Allergy or hypersensitivity to tomatoes and tomato products, gadolinium and history of any other significant atopy/allergy (e.g. soy, whey, lutein, lecithin), Contraindications for MRI studies including claustrophobia, any MRI non-compatible devices implanted (vascular clips, metal sutures, craniofix, cardiac pacers, endovascular stents/coils, etc.), Known renal impairment with creatinine clearance <50 ml/min (as per departmental policy), Women of childbearing potential, Inability to consent

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tomato extract (Ateronon)<br>Supplementation of tomato extract containing 28 mg/day for 12 months in addition to routine treatment. | Dietary Supplement: Ateronon<br>* Tomato extract containing 28 mg lycopene/ day<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plaque morphology and biomechanics on magnetic resonance | Magnetic resonance imiging (MRI) of the plaques will be performed with detailed assessment of plaque morphological parameters: fibrous cap, lipid rich necrotic core, intraplaque hemorrhage. Sheer stress and wall stress will be calculated using magnetic resonance data. | 12 months | 
| Serum levels of lycopene - a component of the tomato extract | Serum levels of lycopene obtained through long-time supplementation with a tomato extract containing lycopene. | 12 months | 
| Microemboli on transcranial Doppler (TCD) | Amount of microeboli detected using bilateral middle cerebral artery (MCA) TCD monitoring (DWL, Germany, 2-MHz probe). TCD will be performed by a single investigator (KPB) for 1 hour | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemistry | Serum levels of total cholesterol, low-denisty lipoproteins (LDL), oxidized-LDL (oxy-LDL), high-density lipoproteins (HDL), C-reactive protein (CRP) as biomarkers of atherosclerosis | 12 months | 
| Levels of blood circulating endothelial cells and endothelial progenitor cells | Levels of blood circulating endothelial cells and endothelial progenitor cells will be measured as markers for endothelial injury | 12 months | 
| Plaque neovascularisation | Plaque enhancement on dynamic contrast-enhanced MRI perfusion imaging using gadolinium-based contrast agent as a surrogate marker for plaque inflammation and neovascularisation. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carotid atheroma, plaque vulnerability, stroke risk