Supplementation of Lycopene in Carotid Atheroma

NCT01102504 | Withdrawn DMC

• 1 other identifier: SOLANUM 2.0.0
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.It decreases lipid oxidation
2. 2.It decreases DNA damage
3. 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).

Conditions

Carotid Atherosclerotic Disease

Keywords

carotid atheroma; plaque vulnerability; stroke risk

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

• Biochemistry

  12 months

• Levels of blood circulating endothelial cells and endothelial progenitor cells

  12 months

• Plaque neovascularisation

  12 months

Study Arms (2)

Tomato extract (Ateronon)

EXPERIMENTAL

Supplementation of tomato extract containing 28 mg/day for 12 months in addition to routine treatment.

Dietary Supplement: Ateronon

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Placebo

Placebo

Ateronon DIETARY_SUPPLEMENT

Tomato extract containing 28 mg lycopene/ day

Tomato extract (Ateronon)

Eligibility Criteria

• Age: 40 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead

Study Sites (1)

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Related Publications (7)

• 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. doi: 10.1161/01.cir.0000041255.88750.f0.

  PMID: 12460866 BACKGROUND

• 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. doi: 10.1016/j.jacc.2005.03.054.

  PMID: 15992643 BACKGROUND

• 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.

  PMID: 19477353 BACKGROUND

• 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.

  PMID: 18294500 BACKGROUND

• 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. doi: 10.1016/s0014-5793(99)00252-5.

  PMID: 10218573 BACKGROUND

• Das S, Otani H, Maulik N, Das DK. Lycopene, tomatoes, and coronary heart disease. Free Radic Res. 2005 Apr;39(4):449-55. doi: 10.1080/10715760500053685.

  PMID: 16032783 BACKGROUND

• Holvoet P, Collen D. Oxidation of low density lipoproteins in the pathogenesis of atherosclerosis. Atherosclerosis. 1998 Apr;137 Suppl:S33-8. doi: 10.1016/s0021-9150(97)00305-5.

  PMID: 9694539 BACKGROUND

MeSH Terms

Conditions

Carotid Artery Diseases

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jonathan H Gillard, FRCR

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident in Neurosurgery

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 13, 2010
• Study Start: August 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: April 1, 2018
• Last Updated: April 6, 2015

Record last verified: 2015-04

Locations

GB (1)