E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Considering the existing data, Actos (pioglitazone) is a promising candidate to improve hemodynamics of various vascular beds by positive effects on endothelial function. This study aims to analyse cerebral, renal, peripheral, and ocular hemodynamics in adults with type 2 diabetes before, during, and after administration of Actos or placebo using the CO2 inhalation test, the Inulin and Paraaminohippuric acid renal clearance, the Venous occlusion plethysmography, and the Retinal Vessel Analyzer. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
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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 |
Changes in the cerebral vasomotor reactivity (CVMR) during and 2 weeks after pioglitazone treatment compared to baseline and placebo |
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E.2.2 | Secondary objectives of the trial |
Changes in the renal glomerular filtration rate (GFR) and renal plasma flow (RPF), the forearm blood flow (FBF), and the retinal vascular reactivity during and 2 weeks after pioglitazone treatment compared to baseline and placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Written informed consent • Age 18 - 95 years • Fasting blood sugar (FBS) > 200 mg/dl and / or HbA1c > 5,9% or antidiabetic treatment • Adequate bilateral temporal bone windows for sufficient TCD examination and symmetrical perfusion of the middle cerebral artery (MCA) • Cardio- / cerebrovascular disease |
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E.4 | Principal exclusion criteria |
General Exclusion Criteria
• Participation in another pharmacologic study in the last 30 days • Known or possible pregnancy or breastfeeding • Cognitive impairment or other reasons interfering with patient compliance • Known malignancy in the last 5 years
Specific Exclusion Criteria
• Hemodynamically relevant stenoocclusive disease of the extracranial and / or intracranial cerebral arteries diagnosed by doppler sonography • TIA or stroke in the last 3 months • Carotid endarteriectomy or angioplasty in the last 3 months • Insulin dependency • Diabetic ketoacidosis • Body mass index (BMI) > 35 kg/m2 • Premedication with thiazolidindiones • Start of treatment with statins in the last 3 months • Start of treatment with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers in the last 3 months • Known drug intolerance against thiazolidindiones • Known drug intolerance against indicator substances (PAH, IN) • Known drug intolerance against tropicamide • Known liver disease (GOT and / or GPT > 2.5 x upper normal limit) • Known renal insufficiency (serum creatinine > 1.2 mg/dl and / or creatinine clearance < 30 ml/min according to the Cockroft formula) • Known microalbuminuria • Known anaemia (haemoglobin < 11 g/dl (male), < 10 g/dl (female)) • Known heart insufficiency (NYHA I-IV) • Advanced pulmonary disease • Known angle-closure glaucoma
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in the cerebral vasomotor reactivity (CVMR) from baseline to end 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.3 |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |