E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Insulin resistance, diastolic cardiac failure, mitochondrial function |
Insuline resistentie, diastolisch hartfalen, mitochondriele functie |
|
E.1.1.1 | Medical condition in easily understood language |
Pre-diabetes and cardiac failure |
Pre-diabetes en hartfalen |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To examine whether ciprofibrate treatment can improve myocardial insulin sensitivity in subjects with IGM (impaired glucose metabolism). |
Onderzoeken of ciprofibraat administratie myocardiale insuline sensitiviteit kan vergroten in personen met IGM. |
|
E.2.2 | Secondary objectives of the trial |
To examine whether ciprofibrate treatment in IGM: • Improves in vivo myocardial mitochondrial function • Lowers intracardiomyocellular lipid content • Improves cardiac diastolic function • Augments hepatic and skeletal muscle glucose uptake • Improves intrahepatic lipid content and composition • Stimulates the PPARα expression and their down-stream targets in humans (measured in skeletal muscle biopsies) |
Onderzoeken of ciprofibraat behandeling in IGM kan: - verbeteren in vivo myocardiale mitochondriele functie - verlagen van intracardiomyocellulaire accumulatie - verbeteren van cardiale diastole functie - vergroten glucose opname door lever en skeletspier - verlagen intrahepatische vetopslag en veranderen vetcompositie in lever - stimuleren PPARa expressie |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Sex: male • Age: 40-70 years • BMI: 27-35 kg/m2 • Stable dietary habits: no weight gain or loss > 5kg in the last three months • Insulin resistant: glucose clearance rate below < 360 ml/kg/min, as determined using OGIS120 |
• Geslacht: man • Leeftijd: 40-70 jaar • BMI: 27-35 kg/m2 • Stabiel gewicht: geen gewichts toename/verlies >5kg in afgelopen 3 maanden • Insuline resistent: glucose klaringsratio < 360 ml/kg/min, zoals bepaald volgens OGIS120 |
|
E.4 | Principal exclusion criteria |
• Patients with a cardiac disease or with instable angina • Haemoglobin <7.8 mmol/l • In case of an abnormal ECG in rest: this will be discussed with the responsible medical doctor • HbA1c > 6.5% • Diagnosed with type 1 or type 2 diabetes mellitus • Use of a fibrate • Medication use known to interfere with glucose homeostasis/metabolism • Use of anti-coagulants, excluding platelet aggregation inhibitors • Subjects who do not want to be informed about unexpected medical findings during the screening /study, or do not wish that their physician is informed, cannot participate in the study. • Subjects who intend to donate blood during the intervention or subjects who have donated blood less than three months before the start of the intervention. • Participation in another biomedical study within 1 month before the first screening visit • Any condition, disease or abnormal laboratory test result that, in the opinion of the Investigator, would interfere with the study outcome, affect trial participation or put the subject at undue risk • Any contra-indication to MRI scanning. • Participation in earlier research or medical examinations in the past 3 months that included PET/MRI scanning |
• Patienten met cardiale ziekten of instabiele angina pectoris • Hemoglobine <7.8 mmol/l • Bij abnormaal rust-ECG: dit wordt besproken met verantwoordelijk afhankelijk arts • HbA1c > 6.5% • Gediagnosticeerd met type 1 of 2 diabetes mellitus • Gebruik van een fibraat • Medicatie dat interfereert met glucose homeostase / metabolisme • Gebruik van anti-coagulantia, behoudens trombocyten aggregatie remmers • Personen die niet geinformeerd willen worden over onverwachte medische bevindingen uit de screening of studie; of zij die niet willen dat hun huisarts wordt geinformeerd. • Personen die bloed willen doneren gedurende de interventie of personen <3 maanden voor aanvang van de interventie bloed hebben gedoneerd • Deelname in een andere biomedische studie <1 maand voor de eerste screenings visite. • Elke omstandigheid, ziekte of abnormaal laboratorium resultaat, die volgens de onderzoeker kan interfereren met de studie uitkomsten of studie deelname beinvloedt of persoon in gevaar kan brengen. • Contra-indicatie voor MRI scanning. • PET scan in afgelopen 3 maanden (in het kader van onderzoek of medisch onderzoek). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Myocardial glucose uptake |
Myocardiale glucose opname |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 35 days supplementation ciprofibrate |
Na 35 dagen toediening ciprofibrate |
|
E.5.2 | Secondary end point(s) |
Insulin sensitivity in clamp procedure |
Insuline gevoeligheid gedurende clamp |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 35 days supplementation ciprofibrate |
Na 35 dagen toediening ciprofibrate |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |