Supplementation of Lycopene in Carotid Atheroma - Full Text View

Purpose

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.

Condition	Intervention
Carotid Atherosclerotic Disease	Drug: Placebo Dietary Supplement: Ateronon

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Basic Science
Official Title:	Supplementation of Lycopene on Carotid Atheroma: Neovascularisation and Morphology (SOLANUM) Study

Resource links provided by NLM:

Drug Information available for: Lycopene

U.S. FDA Resources

Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:

Plaque morphology and biomechanics on magnetic resonance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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.
Serum levels of lycopene - a component of the tomato extract [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Serum levels of lycopene obtained through long-time supplementation with a tomato extract containing lycopene.
Microemboli on transcranial Doppler (TCD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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

Secondary Outcome Measures:

Biochemistry [ Time Frame: 12 months ] [ Designated as safety issue: No ]
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
Levels of blood circulating endothelial cells and endothelial progenitor cells [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Levels of blood circulating endothelial cells and endothelial progenitor cells will be measured as markers for endothelial injury
Plaque neovascularisation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
Plaque enhancement on dynamic contrast-enhanced MRI perfusion imaging using gadolinium-based contrast agent as a surrogate marker for plaque inflammation and neovascularisation.

Estimated Enrollment:	80
Study Start Date:	August 2010
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tomato extract (Ateronon) Supplementation of tomato extract containing 28 mg/day for 12 months in addition to routine treatment.	Dietary Supplement: Ateronon Tomato extract containing 28 mg lycopene/ day
Placebo Comparator: Placebo Placebo	Drug: Placebo Placebo

Eligibility

Ages Eligible for Study:	40 Years to 90 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01102504

Contacts

Contact: Karol P Budohoski, MD

(0044)1223331763 ext 72831763

kpb26@cam.ac.uk

Locations

United Kingdom
Addenbrooke's Hospital	Not yet recruiting
Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
Contact: Jonathan H Gillard, FRCR (0044)1223 336890 jhg21@cam.ac.uk
Contact: Karol P Budohoski, MD (0044)1223 331763 kpb26@cam.ac.uk
Principal Investigator: Jonathan H Gillard, FRCR

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

Cambridge Theranostics Ltd

Investigators

Principal Investigator:

Jonathan H Gillard, FRCR

University Department of Radiology, University of Cambridge, Addenbrooke's Hospital, Hills Road, CB2 0QQ Cambridge, UK

More Information

Publications:

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.

Corti R, Fuster V, Fayad ZA, Worthley SG, Helft G, Chaplin WF, Muntwyler J, Viles-Gonzalez JF, Weinberger J, Smith DA, Mizsei G, Badimon JJ. Effects of aggressive versus conventional lipid-lowering therapy by simvastatin on human atherosclerotic lesions: a prospective, randomized, double-blind trial with high-resolution magnetic resonance imaging. J Am Coll Cardiol. 2005 Jul 5;46(1):106-12.

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.

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. Epub 2008 Jan 18. Erratum in: Am Heart J. 2008 Jun;155(6):1127.

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.

Das S, Otani H, Maulik N, Das DK. Lycopene, tomatoes, and coronary heart disease. Free Radic Res. 2005 Apr;39(4):449-55.

Holvoet P, Collen D. Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis. 1998 Apr;137 Suppl:S33-8. Review.

Responsible Party:	Dr Jonathan H Gillard, Honorary Consultant Professor in Neuroradiology, University of Cambridge
ClinicalTrials.gov Identifier:	NCT01102504 History of Changes
Other Study ID Numbers:	SOLANUM 2.0.0
Study First Received:	April 12, 2010
Last Updated:	August 17, 2010
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:

carotid atheroma
plaque vulnerability
stroke risk

Additional relevant MeSH terms:

Plaque, Atherosclerotic
Carotid Artery Diseases
Pathological Conditions, Anatomical
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Lycopene

Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Radiation-Protective Agents
Anticarcinogenic Agents
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 16, 2013

Supplementation of Lycopene in Carotid Atheroma (SOLANUM)