A 52 week double blind randomised controlled trial comparing the effect of rosiglitazone versus placebo on the prevention of progression of atherosclerosis in high risk patients without diabetes

ISRCTN	ISRCTN54951661
DOI	https://doi.org/10.1186/ISRCTN54951661
Protocol serial number	P04.232; NTR307
Sponsor	Leiden University Medical Centre (LUMC) (Netherlands)
Funder	GlaxoSmithKline (Netherlands)

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 05/04/2012

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 R. Alizadeh Dehnavi
Scientific

Leiden University Medical Centre (LUMC)
P.O. Box 9600
Leiden
2300 RC
Netherlands

Email	R.Alizadehdehnavi@lumc.nl

Study information

Primary study design	Interventional
Study design	Randomised double blind placebo controlled parallel group trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title
Study acronym	RUBENS
Study objectives	The metabolic syndrome and its visceral adiposity may well be beneficially influenced by peroxisome proliferator-activated receptor (PPAR)-alpha agonist, by redistributing fat mass from central to peripheral stores and improving insulin resistance. The inflammatory atherosclerotic response, as monitored by C-reactive protein (CRP), may also directly be beneficially influenced by PPAR-alpha agonists in human subjects. In addition, we hypothesise that thiazolidinediones will beneficially influence intima-media thickness (IMT) in subjects with the metabolic syndrome as defined by the inclusion criteria.
Ethics approval(s)	Received from the local medical ethics committee
Health condition(s) or problem(s) studied	Metabolic syndrome, atherosclerosis
Intervention	1. Lifestyle intervention 2. Rosiglitazone 8 mg (4 mg twice daily [bd]) versus placebo
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Rosiglitazone
Primary outcome measure(s)	1. Magnetic resonance (MR) assessment of the carotid artery wall 2. MR-measured hepatic, intra-abdominal and peripheral subcutaneous fat stores
Key secondary outcome measure(s)	1. Assessment of the changes in selected inflammatory and metabolic parameters amongst which changes in insulin resistance and inducible nitric oxide synthase (iNOS) 2. Cross-sectional assessment of the relation between the characteristics of the magnetic resonance image of the carotid arterial wall and circulating endothelial progenitor cells 3. The effect of rosiglitazone on CEPs after one year of treatment in subjects with high cardiovascular risk without diabetes mellitus 4. Optimalisation of MR assessment of (complex) atherosclerotic plaques and other cardiovascular risk markers
Completion date	01/04/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target sample size at registration	116
Key inclusion criteria	1. Males 2. Age: males greater than or equal to 50 years 3. Visceral obesity as determined by Wcr: males: greater than 94 cm 4. Two other metabolic syndrome criteria (According to IDF criteria 2005) and/or a positive family history for cardiovascular disease (coronary heart disease [CHD] and/or peripheral arterial disease [PAD] in first degree family member: males less than 55 years; females less than 60 years) 5. CRP greater than 1.8 mg/L 6. Subject who is willing and is able to provide a signed and dated written informed consent
Key exclusion criteria	1. Severe obesity (body mass index [BMI] greater than 35 kg/m^2) 2. Diabetes type 2 defined as fasting venous plasma glucose greater than 70 mmol/L, or HbA1c greater than 65% 3. Primary dyslipidaemia 4. A previous cardiovascular event, including Q-wave infarction on electrocardiography (ECG) 5. QTc time interval on baseline ECG greater than 450 ms 6. Heart failure New York Heart Association (NYHA) class I or higher 7. Hypoglycaemia 8. Presence of clinically significant hepatic disease (i.e., subjects with alanine aminotransferase [ALT], total bilirubin, or alkaline phosphatase greater than 25 times the upper limit of the normal laboratory range) 9. Subjects with creatinine clearance less than 40 mL/min calculated using the Cockcroft-Gault equation adjusted for ideal body weight 10. Contraindication for magnetic resonance imaging (MRI)-assessments 11. Risk of non-compliance
Date of first enrolment	26/09/2005
Date of final enrolment	01/04/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Centre (LUMC)

Leiden
2300 RC
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	28/10/2011		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes