E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Obesity, dyslipidemia and impaired glucose tolerance |
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E.1.1.1 | Medical condition in easily understood language |
Obesity and associated disorders such as impaired metabolism of lipids and glucose |
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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 |
The main object of the trial is to evaluate the effect of sitagliptin treatment on BAT activity in overweight, pre-diabetic subjects. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to assess the effect of sitagliptin treatment on 1) resting energy expenditure, 2) muscle glucose metabolism, 3) fat mass, 4) glucose metabolism and 5) plasma lipid levels in overweight, pre-diabetic subjects |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male volunteers, 30 Caucasians, born in the Netherlands - Age: 35-50 years - BMI ≥ 25 and ≤ 30 kg/m2 - Plasma glucose levels 2 h after OGTT between 7.8 and 11 mM (e.g. impaired glucose tolerance)
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E.4 | Principal exclusion criteria |
- Diabetes mellitus (determined on basis of oral glucose tolerance test (OGTT) defined by ADA criteria (22) - BMI > 30 kg/m2 or < 25 kg/m2 - Plasma glucose levels 2 h after OGTT < 7.8 mM or > 11,1 - Use of medication known to influence glucose and/or lipid metabolism or BAT activity (e.g. beta blockers) - Any significant chronic disease - Renal, hepatic or endocrine disease - Smoking - Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study - Difficulties to insert an intravenous catheter - Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
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E.5 End points |
E.5.1 | Primary end point(s) |
BAT volume and activity measured by 18F-FDG PET-CT scan |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Before and after 12 weeks of treatment |
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E.5.2 | Secondary end point(s) |
- Fasted thermoneutral and cold-induced REE by indirect calorimetric - Expression of several biomarkers for insulin signaling and glucose and lipid metabolism in skeletal muscle biopsies measured by RT-PCR and Western Blot - Body weight and fat mass measured by DXA scan - Fasting serum markers for glucose metabolism (glucose, insulin, HbA1c and C-peptide) - Fasting serum markers for lipid metabolism (total cholesterol, HDL-C, LDL-C, triglycerides, free fatty acids)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Before and after 12 weeks of treatment |
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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 | 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 | No |
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 | 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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The trial is ended after 12 weeks of treatment and after the subjects has visited the research center for the last time (approximately 2 weeks after the end of the treatment) |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |