|- candidate number||1309|
|- NTR Number||NTR180|
|- Date ISRCTN created||20-dec-2005|
|- date ISRCTN requested||18-okt-2005|
|- Date Registered NTR||5-sep-2005|
|- Secondary IDs||N/A |
|- Public Title||Pioglitazone Influence of triglyceride Accumulation in the Myocardium in Diabetes.|
|- Scientific Title||Pathophysiological significance of myocardial triglyceride accumulation in type 2 diabetes mellitus related heart disease: the effect of pioglitazone versus metformin on myocardial metabolism and function.|
|- ACRONYM||The PIRAMID study|
|- hypothesis||Lipotoxicity-related cardiac abnormalities can be reversed by PPAR g agonist therapy in type 2 diabetes patients.|
|- Healt Condition(s) or Problem(s) studied||Diabetes Mellitus Type 2 (DM type II), Heart diseases|
|- Inclusion criteria||Type 2 Diabetes PatientsMales, 45-65 years, DM2 (diagnosed according to WHO criteria, treated by monotherapy of sulfanylurea (i.e. unchanged during >30 days prior to inclusion). |
At least three month stable HbA1c (<8.5%) under this therapy.
Sitting blood pressure <150/85 mmHg with or without antihypertensive drugs, BMI<32 kg/m2.Healthy volunteers, Healthy male subjects, 45-65 years, Normal sitting blood pressure <150/85 mmHg, BMI<32 kg/m2. Normal glucose tolerance as assessed by 75-g oral glucose tolerance test.
|- Exclusion criteria||Type 2 Diabetes Patients, CAD, Active malignant disease, Impaired renal function (serum creatinine > 176 mmol/L), Weight >/= 45 kg (because of 11C-palmitate tracer), Anti-coagulant therapy, Severe
obstructive lung disease; hereditary lipoprotein disease, Impaired hepatic function (defined as ALT > 3 ULN) or a history of liver disease, Inability to understand study information, inability / unwillingness to sign informed consent, Substance abuse, Familial polyposis coli, <3 months after participation in other clinical trials. |
Other research projects, whereby radiation is used. Hemoglobin <8 mmol/l, Metal implants and claustrophobia, incompatible with CMR.
Congestive heart failure (NYHA functional score > I), atrial fibrillation or history of sustained ventricular tachycardia.
Stroke within 6 months prior to enrollment.
Microvascular complications, including:
diabetic nephropathy, proliferative retinopathy, symptomatic macrovascular complications and/or (autonomic) neuropathy, except for background diabetic retinopathy.
Leg ulcers, gangrene. Hyper sensibility to study medication.
Current use of TZD/fibrates Healthy volunteersHistory or current cardiovascular diseaseDyslipidemia, requiring pharmacological treatment according to the Dutch Cholesterol Consensus 1998
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-sep-2004|
|- planned closingdate||15-jan-2007|
|- Target number of participants||90|
|- Interventions||80 subjects on monotherapy sulfanylurea for at least 10 weeks will be enrolled. Following, participants will be randomised to Metformin or Pioglitazone for 24 weeks.|
Group 1: Metformin;
Group 2: Pioglitazone
10 healthy subject will only undergo baseline measurements.
|- Primary outcome||Changes in cardiac function and metabolism following treatment with PPARg agonist versus current state of the art therapy, metformin.|
|- Secondary outcome||Glucose and FFA uptake by adipose tissue and skeletal muscle Cardiac high-energy-phosphate (HEP) metabolism. |
Hemodynamic and vascular parametersBody composition (body mass index (BMI), waist, adipose tissue distribution, including liver fat content, body fat percentage and fluid retention) Plasma parameters of glycemic control and lipoprotein metabolism Circulating levels of markers of inflammation, coagulation activation, fibrinolysis and endothelial functions Whole-body insulin sensitivity (by clamp).
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Drs. L.J. Rijzewijk|
|- CONTACT for SCIENTIFIC QUERIES||Dr. M. Diamant|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|Eli Lilly Nederland B.V.|
|- Brief summary||Background/hypothesis:|
Patients with type 2 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 (PPAR) g agonist. Metformin, the present gold standard treatment for type 2 diabetes, might also have cardioprotective properties due to its recently proposed mechanism of action.
|- Main changes (audit trail)|
|- RECORD||29-aug-2005 - 15-nov-2009|