Condition category
Circulatory System
Date applied
03/03/2006
Date assigned
29/03/2006
Last edited
21/09/2011
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Jonathan Gillard

ORCID ID

Contact details

University Department of Radiology
Box 219
Level 5
Cambridge University Hospitals Foundation Trust
Hills Road
Cambridge
CB2 2QQ
United Kingdom
+44 (0)1223 336896
jhg21@cam.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

Acronym

ATHEROMA

Study hypothesis

This study will test the hypothesis that the treatment with atorvastatin 80 mg will demonstrate measurable changes in USPIO-enhanced MRI within the first three months of therapy. If this hypothesis is confirmed, this will provide additional clinical validation of USPIO-enhanced MRI methodology for the screening and the assessment of therapeutic response to anti-inflammatory interventions in patients with high-risk atherosclerotic lesions.

Ethics approval

This study was approved by the Local Regional Ethics Committee, Cambridge, UK on 3/02/2006, reference number: 05/Q0108/441

Study design

Double blind randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

Carotid atherosclerosis

Intervention

Patients with USPIO positive carotid plaques on MRI will be randomised into a high-dose or low-dose atorvastatin group. The high-dose statin group will receive 80 mg atorvastatin daily for 12 weeks and the low dose group will receive 10 mg atorvastatin. High resolution MRI will be performed at baseline, 6 weeks and at 12 weeks.

Intervention type

Drug

Phase

Not Specified

Drug names

Atorvastatin

Primary outcome measures

To establish whether inflammatory activity of the atherosclerotic plaque, as measured by USPIO-enhanced MRI, can be modified after the administration of high- or low-dose atorvastatin

Secondary outcome measures

1. To investigate MRI-derived tensile stress in carotid plaques following the administration of high- or low-dose atorvastatin
2. To quantify changes in cerebral micro-embolisation occurring in patients with carotid plaques treated with high- and low-dose atorvastatin
3. To investigate the effects of high- and low-dose atorvastatin on selected soluble plasma biomarkers
4. To compare macrophage content as determined by USPIO/MRI with histology in carotid atheroma plaques following the administration of high or low dose atorvastatin
5. To assess appearance of new lesions on brain MRI and correlate these with USPIO uptake in the carotid plaque and micro-embolic burden
6. To assess the pharmacokinetic parameters of atorvastatin

Overall trial start date

01/04/2006

Overall trial end date

01/04/2009

Reason abandoned

Eligibility

Participant inclusion criteria

A subject will be eligible for inclusion in this study only if all of the following criteria are met:
1. Signed written informed consent prior to beginning study-related procedures (subject must understand the aims, investigational procedures and possible consequences of the study)
2. Male or female aged 18 to 80 years of age at screening. Female subjects must be of non-childbearing potential (post-menopausal females who have been amenorrheic >1 year, or pre-menopausal females with a documented hysterectomy or bilateral oophorectomy).
3. Positive USPIO-enhanced MRI of carotid plaque confirmed by a consultant neuroradiologist. This will be pre-defined.
4. Must either be statin naive or have been on a stable dose of a statin for ≥4 weeks prior to screening, with no evidence of statin intolerability

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40

Participant exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Required continued use of non-statin lipid modifying therapies
2. History of statin intolerance
3. History of chronic viral hepatitis or other chronic hepatic disorders
4. Renal impairment
5. History of myopathy or inflammatory muscle disease
6. Doppler assessment of less than 40% stenosis during screening assessment
7. Contraindication to MRI scanning
8. Planned carotid surgery or endovascular intervention earlier than 10 weeks within the study period
9. Serum triglycerides >400 mg/dl (4.52 mmol/l) at screening
10. Patients with poorly controlled diabetes mellitus and hypertension
11. History of malignancy
12. Evidence of recent severe infection
13. Current life-threatening condition other than vascular disease
14. Alcohol or drug abuse within the past six months
15. Concomitant use of potent CYP450 3A4 inhibitors
16. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) and oral steroids therapy
17. Chronic use of immunosuppressants
18. Use of an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication
19. Any other subject the investigator deems unsuitable for the study (e.g. due to either medical reasons, laboratory abnormalities, expected study medication non-compliance, or subject’s unwillingness to comply with all study-related procedures)
20. Inability to give informed consent

Recruitment start date

01/04/2006

Recruitment end date

01/04/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University Department of Radiology
Cambridge
CB2 2QQ
United Kingdom

Sponsor information

Organisation

GlaxoSmithKline (UK)

Sponsor details

Greenford Road
Greenford
Middlesex
UB6 OHE
United Kingdom
+44 (0)208 9047500
Andrew.P.Brown@gsk.com

Sponsor type

Industry

Website

Funders

Funder type

Industry

Funder name

GlaxoSmithKline (GSK)

Alternative name(s)

GlaxoSmithKline Plc., GSK

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21483158

Publication citations

  1. Results

    Li ZY, Tang TY, Jiang F, Zhang Y, Gillard JH, Reduction in arterial wall strain with aggressive lipid-lowering therapy in patients with carotid artery disease., Circ. J., 2011, 75, 6, 1486-1492.

Additional files

Editorial Notes