E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 |
Rationale for the study: This project investigates the effect of ACE-inhibition on cellular metabolism by gene expression profiling of human muscle tissue, obtained by biopsy prior to and after ramipril intake. This should contribute to our understanding of the pathomechanisms involved in diabetes and the clinical effect of ACE-inhibition on patients with diabetes/metabolic syndrome.
Aims of the study: To identify and describe metabolic/signaling pathways in muscle tissue which are affected or induced by ACE-inhibition. This might help to identify targets which could serve as early molecular markers of metabolic disease and success of therapy applicable in a clinical setting.
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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 |
• Male • Healthy defined as absence of relevant disease • Caucasian • Aged 18-45 years • BMI: 18-28 kg/m2 • Signed informed consent • Blood pressure between 110/45 and <140/90 (twice at screening)
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E.4 | Principal exclusion criteria |
• History of renal artery stenosis, angioneurotic edema, psoriasis, relevant renal diseases • RR at screening < 110/45 mmHg. • Diabetes, history of hypertension, RR > 140/90 at screening, cardiovascular disease • Known Diabetes mellitus of parents • HIV or Hepatitis B/C positive virology • Allergy or hypersensitivity against ACE-inhibitors / ramipril or to xylocain • Contraindications against the use of the drug according to the SmPC, history of angioedema • Any drug intake 2 weeks prior to first study day • History of excessive bleeding tendency / hemophilia • Presence of relevant illness within the last 3 weeks • Suspected non-compliance with study instructions and life-style requirements • Alcohol or drug abuse • Blood/Plasma donation within 4 weeks prior to study day • Previous exposure to antihypertensive drugs, ACE-inhibitors, in particular ramipril • Current smoking (any quantity), (at least 6 months of non-smoking required)
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E.5 End points |
E.5.1 | Primary end point(s) |
Genome-wide gene expression measurements in skeletal muscle at baseline and in response to ramipril intake. Effects common to all subjects as well as intra-individual differences will be identified and analyzed. Study goal is identification of genes encoding e.g. metabolic proteins, whose expression in muscle tissue is modified by ramipril.
Optional outcome parameters: Previously described single nucleotide polymorphisms in genes of the renin-angiotensin-aldosterone system may be determined from stored blood optionally if further clarification is requested to interpret potential inter-individual differences of gene expression profiles.
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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 | Yes |
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 | Yes |
E.8.1.4 | Double blind | No |
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.8.3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |