E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adults with type 2 diabetes mellitus |
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E.1.1.1 | Medical condition in easily understood language |
Adults with type 2 diabetes mellitus |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
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 assess the effects of 26 weeks Liraglutide treatment on cardiac function in type 2 diabetes mellitus (DM2) of Western European and South Asian origin. |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of 26 weeks Liraglutide treatment on vascular function, glycemic control, fat distribution and brown adipose tissue in DM2. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient group: • Informed consent Western European origin: • Age > 18 years and < 70 years • BMI > 25 kg/m2 • DM2 treated with metformin, metformin + SU derivative, metformin + SU derivative + insulin, or metformin + insulin for at least 3 months in the maximum tolerable dosage • HbA1c ≥ 7% and ≤ 10.0 % • EGFR > 60 ml/min • Normal sitting blood pressure: systolic blood pressure < 140 mm Hg and stable for at least one month South Asian origin: • Age > 18 years and < 75 years • BMI > 23 kg/m2 • DM2 treated with metformin and/or SU derivative and/or insulin for at least 3 months in stable dosage • HbA1c ≥ 6.5% and ≤ 11.0 % • EGFR > 30 ml/min |
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E.4 | Principal exclusion criteria |
Patient group: • Use of thiazolidinediones (TZD), GLP-1 analogues, DPP-IV inhibitors, fibrates, prednisone, cytostatic or antiretroviral therapy within 6 months prior to the study • Hereditary lipoprotein disease • Psychiatric disorders and / or use of antipsychotic or antidepressant drugs at present or in the past • Hepatic disease (AST/ALT > 2 times reference values) • Endocrine disease other than diabetes mellitus type 2 • Any significant chronic disease (e.g. inflammatory bowel disease) • Any significant abnormal laboratory results found during the medical screening procedure • Gastrointestinal surgery (e.g. gastric bypass) • Pregnant woman or a woman who is breast-feeding • Female of child-bearing potential intending to become pregnant or is not using adequate contraceptive methods while sexually active • Allergy to intravenous contrast • Known or suspected hypersensitivity to trial products or related products • Chronic pancreatitis or previous acute pancreatitis • Personal history or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia type 2 • Claustrophobia • Metal implants or other contraindications for MRI • Recent participation in other research projects within the last 3 months or participation in 2 or more projects in one year
Western European origin: • History or presence of cardiovascular disease
South Asian origin: • Uncontrolled treated or untreated hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 110 mmHg) • Acute coronary or cerebrovascular event within 30 days prior to study • Congestive heart failure NYHA III-IV
Healthy control group: • Known acute or chronic disease based on history (which is of influence on primary/secondary outcome measures, at the discretion of the investigator) and physical examination and standard laboratory tests (blood counts, fasting blood glucose, lipids, eGFR, liver enzymes, and electrocardiogram) • Chronic use of any drug (which is of influence on primary/secondary outcome measures, at the discretion of the investigator) and impaired glucose tolerance (as excluded by a 75-g oral glucose tolerance test) • Pregnant woman or a woman who is breast-feeding • Female of child-bearing potential intending to become pregnant or is not using adequate contraceptive methods while sexually active • Allergy to intravenous contrast • Claustrophobia • Metal implants or other contraindications for MRI |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Systolic function: stroke volume, ejection fraction, cardiac output, cardiac index, peak ejection rate • Diastolic function: early peak filling rate (E), early deceleration peak (E dec peak), atrial peak filling rate (A), E/A ratio, peak mitral annulus longitudinal motion (Ea), MR estimate of LV filling pressure (E/Ea)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patient group: Baseline and after 26 weeks Healthy control group: Baseline |
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E.5.2 | Secondary end point(s) |
Heart dimensions including: • End-diastolic volume, end-systolic volume, LV mass, LV mass index, LVMI/EDVI, percentage scar tissue
Aorta and carotid vessel wall imaging including: • Total vessel wall area, average vessel wall thickness, minimum vessel wall thickness, maximum vessel wall thickness, distensibility • Carotid artery intima media thickness (IMT), measured by echography
Body fat distribution: • Adipose tissue distribution, including visceral and subcutaneous fat volume at level of L4-L5, total body fat distribution, brown adipose tissue • Epicardial fat volume • ¹H-MR spectroscopy of the heart, liver, and kidney triglyceride content
Glycemic control: - HBA1C and fasting blood glucose levels
Energy expenditure: - Indirect calorimetry |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
MRI Baseline and after 26 weeks, glycemic control every four weeks
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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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Healthy control group, observational |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Healthy control group, no intervention |
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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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |