Pioglitazone Influence of triglyceRide Accumulation in the Myocardium In Diabetes

ISRCTN	ISRCTN53177482
DOI	https://doi.org/10.1186/ISRCTN53177482
Secondary identifying numbers	NTR180

Submission date: 20/12/2005
Registration date: 20/12/2005
Last edited: 31/01/2012

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

Dr L J Rijzewijk
Scientific

Diabetes Centre/Department of Endocrinology
VU medisch centrum
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Study information

Study design	Multicentre, randomised, double blinded, active controlled, parallel group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title
Study acronym	The PIRAMID study
Study objectives	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.
Ethics approval(s)	Ethics approval received from the local medical ethics committee
Health condition(s) or problem(s) studied	Diabetes Mellitus type two (DM2), heart disease
Intervention	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.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Metformin or Pioglitazone
Primary outcome measure	Changes in cardiac function and metabolism following treatment with PPARg agonist versus current state of the art therapy, metformin.
Secondary outcome measures	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)
Overall study start date	01/09/2004
Completion date	01/09/2006

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Sex	Male
Target number of participants	90
Key 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
Key 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
Date of first enrolment	01/09/2004
Date of final enrolment	01/09/2006

Locations

Countries of recruitment

Netherlands

Study participating centre

Diabetes Centre/Department of Endocrinology

Amsterdam
1081 HV
Netherlands

Sponsor information

VU University Medical Centre (Netherlands)
University/education

Van der Boechorststraat 7
Amsterdam
1081 BT
Netherlands

Website	http://www.vumc.nl/english/
"ROR"	https://ror.org/00q6h8f30

Funders

Funder type

Industry

Eli Lilly Nederland B.V. (Netherlands)

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	Peer reviewed?	Patient-facing?
Results article	results	21/04/2009	Yes	No
Results article	results	01/07/2010	Yes	No
Results article	results	19/07/2011	Yes	No