E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity, overweight, lipid- and glucose metabolism |
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E.1.1.1 | Medical condition in easily understood language |
In this study we will investigate whether we can activate energy-burning brown adipose tissue to combat overweight, obesity and associated cardio metabolic diseases, such as diabetes. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029885 |
E.1.2 | Term | Obesity, unspecified |
E.1.2 | System Organ Class | 100000004861 |
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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 investigate the acute effect of ADRB2 activation, via intravenous administration of salbutamol (250 μg), on 18F-FDG uptake by BAT.
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E.2.2 | Secondary objectives of the trial |
- To assess the acute effect of ADRB2 activation via intravenous administration of salbutamol (250 μg) on resting energy expenditure, serum markers for lipid- and glucose metabolism and plasma BAT markers. - To confirm that the stimulatory effect of salbutamol on 18F-FDG uptake by BAT is not mediated via the ADRB3, by showing that the acute effect of i.v. salbutamol (250 μg) on BAT is blunted by co-administration of the ADRB1/2-blocker propranolol. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Dutch white Caucasian males - Age between 18-35 years old - Lean (BMI ≥ 18 and ≤ 25 kg/m2) |
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E.4 | Principal exclusion criteria |
- Diabetes mellitus (determined on basis of fasting glucose levels defined by ADA criteria) - Any other active endocrine disease (thyroid disease, any signs of Cushing’s syndrome, adrenal disease and lipid-associated disorders such as familial hypercholesterolemia) - Any cardiac disease (i.e. ischemic cardiac disease, arrhythmias, severe heart failure) - A first-degree family member with sudden cardiac death - Any chronic renal or hepatic disease - Use of beta-adrenergic receptor agonists (for e.g. asthma) - Use of medication known to influence glucose and/or lipid metabolism or brown fat activity (e.g. beta-blockers, antidepressants, corticosteroids) - Use of medication shown to increase risk on hypokalemia after salbutamol administration (e.g. xanthine derivatives, steroids and diuretics) - Any other contra-indications for the use of salbutamol or propranolol - Abuse of alcohol or other substances - Smoking - Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study - Current participation in another research projects that may influence the current research project - Participation in another research in which a PET-CT scan was performed within a year before the start of the current study - Clinically relevant abnormalities in clinical chemistry or electrocardiogram (ECG) at screening (to be judged by the study physician) |
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E.5 End points |
E.5.1 | Primary end point(s) |
- Glucose uptake by BAT, as measured by dynamic 18F-FDG PET/CT acquisition |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After completion of the study |
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E.5.2 | Secondary end point(s) |
- Resting energy expenditure, as measured by indirect calorimetry - Serum markers for lipid metabolism (triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), free fatty acids) - Lipid pathway analysis using lipidomic analysis in plasma samples - Serum markers for glucose metabolism (glucose, insulin) - Circulating plasma BAT markers (e.g. microRNAs) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After completion of the study |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | 1 |
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
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End of the trial is defined by completion of the last visit of the last subject. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |