A 6 Month Randomised, Double-Blind, Placebo-Controlled, Magnetic Resonance Spectroscopy (MRS) and Imaging Study to Evaluate the Effect of Rosiglitazone on the Intrahepatic and Intramyocellular Lipid content in Subjects with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease
| ISRCTN | ISRCTN51254253 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN51254253 |
| Secondary identifying numbers | N/A |
- Submission date
- 18/08/2005
- Registration date
- 01/09/2005
- Last edited
- 18/01/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Desmond Johnston
Scientific
Scientific
Metabolic Medicine Department
2nd Floor, Mint Wing
St Mary's Hospital
Winsland Street
London
W2 1NY
United Kingdom
| Phone | +44 (0)207 886 1209 |
|---|---|
| d.johnston@imperial.ac.uk |
Study information
| Study design | Randomised, Double-Blind, Placebo-Controlled |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study acronym | RAFL |
| Study objectives | 1. Changes in fat deposition in the liver are reflected by metabolite abnormalities that can be detected non-invasively by in vivo hepatic 1H MRS 2. Multinuclear in vivo MRS may determine differences in the type of fat deposited in the liver with differing aetiology and allow the progression of steatosis to fibrosis to be followed non-invasively 3. Non-Alcoholic Steatohepatitis (NASH) in Type 2 Diabetic Patients may improve with treatment with Rosiglitazone 4. Dyslipidaemia in non-alcoholic steatohepatitis may be reversed by Rosiglitazone |
| Ethics approval(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | Type 2 Diabetic Patients with Non-Alcoholic Fatty Liver Disease |
| Intervention | Rosiglitazone (4-8 mg/day) vs placebo |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Rosiglitazone |
| Primary outcome measure | The primary aim is to evaluate, using magnetic resonance imaging and spectroscopy (MRI and MRS), the effect of 26 weeks oral treatment with rosiglitazone in comparison to placebo on the change from baseline of intra-abdominal and sub-cutaneous adipose tissue volume, in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease or steatohepatitis and liver fat content as assessed by MRS. |
| Secondary outcome measures | Secondary objectives are to evaluate the effects of rosiglitazone on the following: glycaemic control, lipids and lipoproteins; insulin sensitivity and secretion using homeostatic model assessment (HOMA); circulating lipoprotein lipase, hepatic lipase, cholesterol ester transferase (CETP) and lecithin cholesterol acyl transferase activity (LCAT) activities; the composition of circulating high density lipoprotein (HDL) and its apolipoprotein A-I (apoA-1) isoforms; biomarkers of systemic inflammation and plaque stability; very low density apolipoprotein B100 (VLDL apoB100) and HDL apoA-I kinetics. |
| Overall study start date | 12/08/2003 |
| Completion date | 31/08/2004 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 20 |
| Key inclusion criteria | 1. Patients with type 2 diabetes 2. Male or female patient who is 30 to 75 years of age, inclusive, at screening 3. Patients who have initiated statin and fibrate therapy at least 6 months prior to screening, and have been receiving a stable dose for at least 3 months prior to screening. Patients not receiving statin or fibrate therapy may enter the study providing that this method of treatment is not required as active treatment for their medical condition at the time of screening. If any of these patients develop the need for statin or fibrate therapy during the course of the study, therapy will be started without the need to withdraw the patient from the study. 4. Female patients must be post-menopausal (i.e. >6 months without menstrual period) or using contraceptive measures 5. Patients with an HbAlc value <10% at screening visit 6. Patients have an elevated alanine aminotransferase activity (ALT) or aspartate aminotransferase activity (AST) or ultrasound appearances of fatty liver |
| Key exclusion criteria | 1. Patients who have taken >2 concomitant oral anti-hyperglycaemic agents (i.e. oral combination) within the 3 months prior to the screening visit (visit 1) 2. Patients who have required the chronic use of insulin for glycaemic control 3. Use of any investigational drug or previous exposure to a thiazolidinedione (TZD) or other PPAR-gamma; agonist (e.g. rosiglitazone, troglitazone, pioglitazone, GI262570) within 30 days or 5 half-lives (whichever is longer) preceding the first dose of medication at the start of the study 4. Systolic blood pressure >170 mmHg or diastolic blood pressure >100 mmHg 5. Patients with unstable or severe angina or congestive heart failure. Presence of clinically significant hepatic disease (i.e. patients with ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of the normal laboratory range). 6. Any pre-existing condition or clinically significant abnormality identified on the Screening (visit 1) physical examination, electrocardiogram, ultrasound examination or laboratory tests which, in the judgement of the investigator, would preclude safe completion of the study 7. Clinically significant anaemia defined by haemoglobin concentration <11 g/dl for males or <10 g/dl for females 8. Patients with creatinine >150 umol/l 9. Women who are lactating, pregnant or planning to become pregnant during the course of the study 10. Alcohol or drug abuse within the last 6 months 11. Patients with chronic liver disease such as viral or autoimmune hepatitis and haemochromatosis 12. Patients with a history of claustrophobia (inability to tolerate MR procedure) 13. Pacemakers, cerebral aneurysm clips, claustrophobia or any implantable ferro-magnetic device incompatible with magnetic resonance imaging |
| Date of first enrolment | 12/08/2003 |
| Date of final enrolment | 31/08/2004 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Metabolic Medicine Department
London
W2 1NY
United Kingdom
W2 1NY
United Kingdom
Sponsor information
Imperial College London (UK)
University/education
University/education
Clinical Research Office
South Kensington campus
London
SW7 2AZ
England
United Kingdom
| clinical.researchoffice@imperial.ac.uk | |
| Website | http://www.imperial.ac.uk |
"ROR" |
https://ror.org/041kmwe10 |
Funders
Funder type
Research council
MRC Career Establishment Grant DMEHEPRO2929 (UK)
No information available
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 | 27/07/2009 | Yes | No |
