A 12-week, randomised, double-blind study evaluating the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on macrophage activity and carotid plaque inflammation as determined by ultra small super-paramagnetic iron oxide (USPIO) enhanced carotid magnetic resonance imaging (MRI)
| ISRCTN | ISRCTN64894118 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64894118 |
| ClinicalTrials.gov number | NCT00368589 |
| Secondary identifying numbers | N/A |
- Submission date
- 03/03/2006
- Registration date
- 29/03/2006
- Last edited
- 10/09/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Jonathan Gillard
Scientific
Scientific
University Department of Radiology
Box 219
Level 5
Cambridge University Hospitals Foundation Trust
Hills Road
Cambridge
CB2 2QQ
United Kingdom
| Phone | +44 (0)1223 336896 |
|---|---|
| jhg21@cam.ac.uk |
Study information
| Study design | Double blind randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | A 12-week, randomised, double-blind study evaluating the effects of low-dose (10 mg) and high-dose (80 mg) atorvastatin on macrophage activity and carotid plaque inflammation as determined by ultra small super-paramagnetic iron oxide (USPIO) enhanced carotid magnetic resonance imaging (MRI) |
| Study acronym | ATHEROMA |
| Study objectives | 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(s) | This study was approved by the Local Regional Ethics Committee, Cambridge, UK on 3/02/2006, reference number: 05/Q0108/441 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Atorvastatin |
| Primary outcome measure | 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 study start date | 01/04/2006 |
| Completion date | 01/04/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 |
| Total final enrolment | 40 |
| Key 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 |
| Key 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 subjects unwillingness to comply with all study-related procedures) 20. Inability to give informed consent |
| Date of first enrolment | 01/04/2006 |
| Date of final enrolment | 01/04/2009 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University Department of Radiology
Cambridge
CB2 2QQ
United Kingdom
CB2 2QQ
United Kingdom
Sponsor information
GlaxoSmithKline (UK)
Industry
Industry
Greenford Road
Greenford
Middlesex
UB6 OHE
United Kingdom
| Phone | +44 (0)208 9047500 |
|---|---|
| Andrew.P.Brown@gsk.com | |
"ROR" |
https://ror.org/01xsqw823 |
Funders
Funder type
Industry
GlaxoSmithKline (GSK)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- GlaxoSmithKline plc., GSK plc., GSK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/06/2011 | Yes | No | |
| Results article | results | 02/06/2009 | 10/09/2019 | Yes | No |
Editorial Notes
10/09/2019: ClinicalTrials.gov number, publication reference and total final enrolment number added.
