E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type 2 diabetes and dyslipidemia |
Type 2 diabetes og dyslipidæmi |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physiological processes [G07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
It is the general purpose of the trial to investigate whether the positive effects of metformin on blood lipids are caused by improved glycemic control and changes in body composition or if they are caused by direct effects on lipid metabolism. We specifically plan to: - investigate hepatic fatty acid uptake, reesterification and oxidation assessed by positron emission tomography (PET) - investigate the effect of metformin on whole body VLDL-TG oxidation and redeposition in adipose tissue. |
Det er undersøgelsens generelle formål at afklare, hvorvidt metformins positive effekt på lipidprofilen er forårsaget af bedre glykæmisk kontrol og eventuelle ændringer i kropssammensætningen eller om det skyldes direkte effekter på omsætningen af lipider. Vi planlægger specifikt - At undersøge metformins effekt på den dynamiske lipidomsætning (fedtsyreoptag, reesterificering og forbrænding) i leveren bedømt ved såvel PET som mere traditionelle isotopundersøgelser. - At undersøge metformins effekt på helkropsomsætningen af VLDL-triglycerid, herunder både forbrænding i muskelvæv og deponering i fedtvæv.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Group 1: Diabetes subjects:
- newly diagnosed (>3 og <12 months) type 2 diabetes - Age 50-70 years - BMI<40
Group 2: Healthy controls
- Age 50-70 years - BMI<40 |
Gruppe 1: patienter med type 2 diabetes
- Nydiagnosticeret (>3 og <12 måneder) Type 2 diabetes - Alder 50-70 år - BMI<40
Gruppe 2: Raske kontroller
- Alder 50-70 år - BMI<40 |
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E.4 | Principal exclusion criteria |
- metformin treatment >6 months - Non-alcoholic steatohepatitis - Cancer - Anaemia - HbA1C>8.5 % - Other clinically meaningful abnormal biochemical parameter - Pancreatitis - Alcohol or substance abuse - Allergy towards metformin - Claustrophobia - Severe obesity >130 kg |
• Metforminbehandling >6 måneder • Leversygdom i form af NASH (non-alkoholisk steatohepatitis) • Cancersygdom • Klinisk betydende anæmi • HbA1C>8.5 % • Anden klinisk relevant abnorm biokemisk værdi • Nuværende eller tidligere kronisk eller akut pankreatitis. • Kendt misbrug af alkohol eller medicin • Kendt allergi overfor metformin eller et af de øvrige indholdstoffer • Klaustrofobi, manglende kooperation af anden vis • Svær overvægt > 130 kg
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E.5 End points |
E.5.1 | Primary end point(s) |
- hepatic FFA uptake ([11C]palmitate – PET technique) - hepatic FFA oxidation ([11C]palmitate – PET technique) - hepatic FFA reesterification ([11C]palmitate – PET technique)
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- FFA optag i leveren ([11C]palmitat – PET teknik) - FFA forbrænding i leveren ([11C]palmitat – PET teknik) - FFA reesterificering i leveren ([11C]palmitat – PET teknik)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months treatment |
Efter 3 måneders behandling |
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E.5.2 | Secondary end point(s) |
- VLDL-TG secretion ([14C]VLDL – isotope dilution technique) - VLDL-TG oxidation (14CO2 in breath) - VLDL-TG redeposition in adipose tissue. (fat biopsy ~ 1 g) - Insulin sensitivity in the liver and peripheral tissues [3H]glucose – isotope dilution technique - Body composition (DEXA) - Intracellular signalling in muscle and adipose tissue (AMPK, LKB1, ACC, CD36, ATGL, HSL, perilipin, G0S1, CGI58, GLUT4, og cytochrom C)
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- VLDL-TG sekretion ([14C]VLDL – isotop fortyndingsteknik) - VLDL-TG forbrænding i muskelvæv (14CO2 i udåndingsluft) - VLDL-TG deponering i fedtvæv. (fedtbiopsi ~ 1 g) - Insulinfølsomhed i lever og perifert væv bestemt ved [3H]glukose – isotop fortyndingsteknik. - Kropssammensætning bestemt ved DEXA før og efter behandling. - Intracellulære signalveje i muskel- og fedtvæv (AMPK, LKB1, ACC, CD36, ATGL, HSL, perilipin, G0S1, CGI58, GLUT4, og cytochrom C)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
3 months treatment |
Efter 3 måneders behandling |
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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 | Yes |
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 | Yes |
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 | 3 |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |