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Pioglitazone Influence of triglyceRide Accumulation in the Myocardium In Diabetes
ISRCTN ISRCTN53177482
DOI 10.1186/ISRCTN53177482
ClinicalTrials.gov identifier
EudraCT number
Public title Pioglitazone Influence of triglyceRide Accumulation in the Myocardium In Diabetes
Scientific title
Acronym The PIRAMID study
Serial number at source NTR180
Study hypothesis Patients with type two Diabetes Mellitus (DM2) have a considerably higher risk to develop cardiac disease with a poorer outcome. Ectopic Triglyceride (TG) accumulation underlies diabetic cardiomyopathy. These cardiac abnormalities can be reversed by lowering myocardial TG using a Peroxisome Proliferator-Activated Receptor-g (PPARg) agonist. Metformin, the present gold standard treatment for type two diabetes, might also have cardioprotective properties due to its recently proposed mechanism of action.

Hypothesis:
Lipotoxicity-related cardiac abnormalities can be reversed by PPAR g agonist therapy in type two diabetes patients.
Lay summary Not provided at time of registration
Ethics approval Ethics approval received from the local medical ethics committee
Study design Multicentre, randomised, double blinded, active controlled, parallel group trial
Countries of recruitment Netherlands
Disease/condition/study domain Diabetes Mellitus type two (DM2), heart disease
Participants - inclusion criteria Type two diabetes patients:
1. Type two diabetes diagnosed male patients aged 45 to 65 years (diagnosed according to World Health Organisation [WHO] criteria)
2. Treated by monotherapy of sulfanylurea (i.e. unchanged during more than 30 days prior to inclusion)
3. At least three months stable HbA1c (less than 8.5%) under this therapy
4. Sitting blood pressure less than 150/85 mmHg with or without anti-hypertensive drugs
5. Body Mass Index (BMI) less than 32 kg/m^2

Healthy volunteers:
1. Healthy male subjects, 45 to 65 years
2. Normal sitting blood pressure less than 150/85 mmHg
3. BMI less than 32 kg/m^2
4. Normal glucose tolerance as assessed by 75 g oral glucose tolerance test
Participants - exclusion criteria Type two diabetes patients:
1. Coronary Artery Disease (CAD)
2. Active malignant disease
3. Impaired renal function (serum creatinine more than 176 mmol/l)
4. Weight greater than or equal to 45 kg (because of 11C-palmitate tracer)
5. Anti-coagulant therapy
6. Severe obstructive lung disease
7. Hereditary lipoprotein disease
8. Impaired hepatic function (defined as Alanine aminotransferase [ALT] more than three Upper Limit of Normal [ULN]) or a history of liver disease
9. Inability to understand study information
10. Inability/unwillingness to sign informed consent
11. Substance abuse
12. Familial polyposis coli
13. Less than three months after participation in other clinical trials or other research projects, whereby radiation is used
14. Haemoglobin less than 8 mmol/l
15. Metal implants and claustrophobia
16. Incompatible with Cardiovascular Magnetic Resonance (CMR)
17. Congestive heart failure (New York Heart Association [NYHA] functional score more than one)
18. Atrial fibrillation or history of sustained ventricular tachycardia
19. Stroke within six months prior to enrolment
20. Microvascular complications including:
a. diabetic nephropathy
b. proliferative retinopathy
c. symptomatic macrovascular complications, and/or
d. (autonomic) neuropathy, except for background diabetic retinopathy, leg ulcers, gangrene, hypersensibility to study medication, current use of Thiazolidinediones (TZD)/fibrates

Healthy volunteers:
1. History or current cardiovascular disease
2. Dyslipidemia, requiring pharmacological treatment according to the Dutch Cholesterol Consensus 1998
Anticipated start date 01/09/2004
Anticipated end date 01/09/2006
Status of trial Completed
Patient information material Not available in web format, please use the contact details below to request a patient information sheet
Target number of participants 90
Interventions 80 subjects on monotherapy sulfanylurea for at least ten weeks will be enrolled. Following this, participants will be randomised to metformin or pioglitazone for 24 weeks. Ten healthy subject will only undergo baseline measurements

Please note that the anticipated end date of this trial has been extended to the 15th January 2007.
Primary outcome measure(s) Changes in cardiac function and metabolism following treatment with PPARg agonist versus current state of the art therapy, metformin.
Secondary outcome measure(s) 1. Glucose and Free Fatty Acid (FFA) uptake by adipose tissue and skeletal muscle
2. Cardiac High-Energy-Phosphate (HEP) metabolism
3. Haemodynamic and vascular parameters body composition (Body Mass Index [BMI], waist, adipose tissue distribution, including liver fat content, body fat percentage and fluid retention)
4. Plasma parameters of glycemic control and lipoprotein metabolism
5. Circulating levels of markers of inflammation, coagulation activation, fibrinolysis and endothelial functions
6. Whole-body insulin sensitivity (by clamp)
Sources of funding Eli Lilly Nederland B.V. (Netherlands)
Trial website
Publications 1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19349323
2. 2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20150294
3. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21771299
Contact name Dr  L J  Rijzewijk
  Address Diabetes Centre/Department of Endocrinology
VU medisch centrum
De Boelelaan 1117
  City/town Amsterdam
  Zip/Postcode 1081 HV
  Country Netherlands
Sponsor VU University Medical Centre (Netherlands)
  Address Van der Boechorststraat 7
  City/town Amsterdam
  Zip/Postcode 1081 BT
  Country Netherlands
  Sponsor website: http://www.vumc.nl/english/
Date applied 20/12/2005
Last edited 31/01/2012
Date ISRCTN assigned 20/12/2005
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