Carotid Atherosclerotic Disease Clinical Trial
— SOLANUMOfficial title:
Supplementation of Lycopene on Carotid Atheroma: Neovascularisation and Morphology (SOLANUM) Study
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:
1. It decreases lipid oxidation
2. It decreases DNA damage
3. 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.
| Status | Withdrawn |
| Enrollment | 0 |
| Est. completion date | April 2018 |
| Est. primary completion date | December 2017 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 40 Years to 90 Years |
| Eligibility |
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: 1. Amaurosis fugax 2. Transient ischemic attack (TIA) 3. 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 |
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science
| Country | Name | City | State |
|---|---|---|---|
| United Kingdom | Addenbrooke's Hospital | Cambridge | Cambridgeshire |
| Lead Sponsor | Collaborator |
|---|---|
| Cambridge University Hospitals NHS Foundation Trust |
United Kingdom,
Carpenter KL, Hardwick SJ, Albarani V, Mitchinson MJ. Carotenoids inhibit DNA synthesis in human aortic smooth muscle cells. FEBS Lett. 1999 Mar 19;447(1):17-20. — View Citation
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Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Smith D, Weinberger J, Wentzel J, Mizsei G, Mercuri M, Badimon JJ. Lipid lowering by simvastatin induces regression of human atherosclerotic lesions: two years' follow-up by high-resolution noninvasive magnetic resonance imaging. Circulation. 2002 Dec 3;106(23):2884-7. — View Citation
Das S, Otani H, Maulik N, Das DK. Lycopene, tomatoes, and coronary heart disease. Free Radic Res. 2005 Apr;39(4):449-55. — View Citation
Holvoet P, Collen D. Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis. 1998 Apr;137 Suppl:S33-8. Review. — View Citation
Tang TY, Howarth SP, Miller SR, Graves MJ, Patterson AJ, U-King-Im JM, Li ZY, Walsh SR, Brown AP, Kirkpatrick PJ, Warburton EA, Hayes PD, Varty K, Boyle JR, Gaunt ME, Zalewski A, Gillard JH. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009 Jun 2;53(22):2039-50. doi: 10.1016/j.jacc.2009.03.018. — View Citation
Underhill HR, Yuan C, Zhao XQ, Kraiss LW, Parker DL, Saam T, Chu B, Takaya N, Liu F, Polissar NL, Neradilek B, Raichlen JS, Cain VA, Waterton JC, Hamar W, Hatsukami TS. Effect of rosuvastatin therapy on carotid plaque morphology and composition in moderately hypercholesterolemic patients: a high-resolution magnetic resonance imaging trial. Am Heart J. 2008 Mar;155(3):584.e1-8. doi: 10.1016/j.ahj.2007.11.018. Epub 2008 Jan 18. Erratum in: Am Heart J. 2008 Jun;155(6):1127. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | No |
| Primary | 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 | No |
| Primary | 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 | No |
| Secondary | 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 | No |
| Secondary | 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 | No |
| Secondary | 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 | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02017756 -
Chinese Atherosclerosis Risk Evaluation- Phase II
|
N/A |