E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes mellitus |
Type 2 diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
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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 determine if prolonged treatment (4 weeks) with the selective beta-2 adrenergic agonist clenbuterol improves in vivo glucose disposal in quadriceps muscle via the mTORC2 pathway in obese male and (postmenopausal) women |
Om te onderzoeken of supplementatie met de selective beta-2 agonist clenbuterol voor een langere tijd (4 weken) de glucose opname in quadriceps spier kan verbeteren via de mTORC2 pathway in obese mannen en (post-menopausale) vrouwen. |
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E.2.2 | Secondary objectives of the trial |
To determine if prolonged treatment (4 weeks) with the selective beta- 2 adrenergic agonist clenbuterol enhances BAT mass and activity in obese male and (postmenopausal) women. |
Om te onderzoeken of supplementatie met de selective beta-2 agonist clenbuterol voor langere tijd (4 weken) de activatie en massa van bruin vet kan verbeteren in obese mannen en (post-menopausale) vrouwen |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or (postmenopausal; defined as 1 year after the last cycle) female; 2. Age between 40-70 years; 3. BMI: 27-35 kg/m2;
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1. Man of (postmenopausaal; gedefinieerd als minimaal 1 jaar na de laatste cyclus) vrouw 2. Leeftijd tussen de 40-70 jaar 3. BMI: 27-35 kg/m2
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E.4 | Principal exclusion criteria |
1. Not meeting all inclusion criteria 2. Cardiovascular disease (determined by means of questionnaires, heart rate/blood pressure measurements and an ECG) 3. Respiratory diseases (including asthma, bronchitis and COPD); 4. Unstable body weight (weight gain or loss > 5 kg in the last three months); 5. Intention to lose or gain body weight (e.g. with caloric restriction or physical activity) 6. Excessive alcohol and/or drug abuse; 7. Hypokalaemia; 8. Hyperthyroidism 9. Anaemia; 10. Epilepsy; 11. Smoking; 12. Renal and/or liver insufficiency; 13. Diagnosed with type 1 or type 2 diabetes mellitus; 14. Any contra-indications to MRI scanning. These contra-indications include patients with: a. Electronic implants such as pacemakers, defibrillators or neurostimulators b. Central nervous system aneurysm clip c. Some hearing aids (such as cochlear implant) and artificial (heart) valves which are contraindicated for MRI/MRS d. Iron containing corpora aliena in the eye or brains e. Claustrophobia 15. Participation in another biomedical study within 1 month before the first study visit, possibly interfering with the study results; 16. Medication use known to hamper subject’s safety during the study procedures;
17. Subjects who do not want to be informed about unexpected medical findings;
18. Subjects who do not want that their treating physician to be informed; 19. Inability to participate and/or complete the required measurements; 20. Participation in organised or structured physical exercise; 21. 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;
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1. Niet voldoen aan alle inclusie criteria 2. Cardiovasculaire ziekten (bepaald a.d.h.v. vragenlijsten, hartslag/bloeddruk en ECG) 3. Luchtwegaandoeningen (inclusief asthma, bronchitis en COPD) 4. Geen stabiel lichaamsgewicht (gewicht toe- of afname van >5 kg in de laatste 3 maanden) 5. Intentie om lichaamsgewicht bij te komen of af te vallen (bijvoorbeeld door calorie restrictie of fysieke activiteit) 6. Overmatig gebruik van alcohol of drugs gebruik 7. Hypokaliëmie 8. Hyperthyroïdie 9. Anemie 10. Epilepsie 11. Roken 12. Nier of lever insuffiëntie 13. Gediagnosticeerd met type 1 of type 2 diabetes mellitus 14. Contra-indicaties voor MRI scanners. Deze contra-indicaties zijn o.a. patiënten met: a. Electronische implantaten zoals pacemakers, defibrillators of neurostimulatoren b. Centrale zenuwstelsel aneurisma clips c. Bepaalde gehoortoestellen (zoals een cochlear implantaat) en kunstmatige (hart) kleppen die niet geschikt zijn voor MRI/MRS d. IJzer bevattende corpora aliena in de ogen of hersenen e. Claustrofobie 15. Deelname aan een andere biomedische studie binnen 1 maand voor de eerste studie dag, die daarbij mogelijk de studie resultaten beïnvloeden. 16. Medicatie waarvan bekend is dat het de veiligheid van de proefpersoon kan beïnvloeden tijdens de studie 17. Proefpersonen die niet willen worden geïnformeerd over onverwachte medische bevindingen 18. Proefpersonen die niet willen dat hun behandelende arts wordt geïnformeerd. 19. Proefpersonen die niet in staat zijn deel te nemen/ de studie af te ronden. 20. Proefpersonen die deelnemen aan gestructureerde fysieke activiteit. 21. Een conditie, ziekte of abnormale laboratorium testuitslag die, in de ogen van de onderzoeker, de resultaten van de studie zouden kunnen beïnvloeden of de proefpersoon zouden blootstellen aan onnodige risico's.
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E.5 End points |
E.5.1 | Primary end point(s) |
insulin-stimulated 18F-FDG uptake in quadriceps muscle (Ki) as assessed by in PET-MRI. |
insuline-gestimuleerde 18F-FDG opname in quadriceps spieren (Ki) gemeten met gehulp van PET-MRI. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Supplementation of clenbuterol/placebo will be 4 weeks. An interim analysis will be performed after the 10th subject. All data will be analysed after finalising the second intervention period of the 14th subject. |
De supplementatie van clenbuterol/placebo zal 4 weken worden gedaan. Een interim analyse zal plaatsvinden na de 10e proefpersoon. Alle data zal worden geanalyseerd nadat de tweede interventie van de 16e proefpersoon is afgelopen |
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E.5.2 | Secondary end point(s) |
Insulin-stimulated 18F-FDG uptake in BAT (expressed as Ki) as assessed by means of PET-MRI |
Insuline gestimuleerde 18F-FDG opname in bruin vetweefsel (uitgedrukt als Ki) zoals gemeten met behulp van PET-MRI |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Supplementation of clenbuterol/placebo will be 4 weeks. An interim analysis will be performed after the 10th subject. All data will be analysed after finalising the second intervention period of the 16th subject. |
De supplementatie van clenbuterol/placebo zal 4 weken worden gedaan. Een interim analyse zal plaatsvinden na de 10e proefpersoon. Alle data zal worden geanalyseerd nadat de tweede interventie van de 16e proefpersoon is afgelopen |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
IMP is used to investigate whether selective beta-2 adrenergic agonist stimulation enhances skeletal muscle glucose uptake through the mTORC2-GLUT4 pathway |
De IMP zal worden gebruikt om te onderzoeken of selectieve beta-2 agonist stimulatie de glucose opname in de spier kan verbeteren via de mTORC2-GLUT4 pathway |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | No |
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 | Yes |
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
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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 | |
E.8.9.1 | In the Member State concerned days | |