E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Type 2 diabetes mellitus (T2DM) whoa re not receiving insulin treatment |
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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 | 10012613 |
E.1.2 | Term | Diabetes mellitus non-insulin-dependent |
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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 investigate the influence of the Pro12Ala genotype on body water and oedema formation, detected by ankle-foot volume assessed by water displacement, in patients with T2DM treated with thiazolidinediones (TZD) |
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E.2.2 | Secondary objectives of the trial |
To evaluate the mechanism and biomarkers of this increased risk by careful investigation of the metabolic, cardiovascualr, and renal responses to TZD in theses individuals.
To examine the efficacy response of pioglitazone (TZD) between the Pro12Ala and Pro12Pro genotypes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Once selected from the DARTS database, patients must fulfill all of the following criteria: 1. Between 30 and 70 inclusive 2. Type 2 diabetes mellitus 3. Non-insulin dependent 4. BMI 20-35 kg/m2 5. HbA1c ≤15% within last 12 months 6. BP ≤160/100 mmHg 7. Ability to understand and willingness to sign the informed consent form 8. Willing to discontinue oral agents for 2 weeks prior to the study 9. Willing to initiate TZD therapy for the duration of the study Patients in cohort 1 must fulfill the following criterion: 1. Genotype Pro12Ala variant of the PPAR-gamma gene Patients in cohort 2 must fulfill the following criterion: 1. Genotype Pro12Pro of the PPAR-gamma gene
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E.4 | Principal exclusion criteria |
Patients in both cohorts are to be excluded from the study if they meet any of the following criteria: 1. Patients with existing peripheral oedema 2. Pregnant or lactating women 3. Known to be HIV-positive 4. Known active hepatitis B and/or hepatitis C infection 5. Patients currently receiving diuretics and/or calcium channel blockers 6. History of symptomatic heart failure (NYHA Classes II, III, IV) or LV systolic ejection fraction <40%) 7. Acute cardiovascular event within 6 months before screening including myocardial infarction, cerebrovascular accident, cardiac disturbance, evidence of acute or unstable chronic pulmonary disease or lesions at chest radiograph 8. History of TZD intolerance or currently receiving TZD therapy 9. Significant renal or hepatic dysfunction (>2.5 xULN ALT; creatinine >130 μmol/L) 10. Known drug/alcohol abuse 11. Known psychiatric condition 12. Patients requiring insulin therapy or more than 2 oral anti-diabetic drugs 13. Microalbuminuria (as detected by standard clinical screening methods) 14. Patients with severe varicose veins |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary aim of the study is: To investigate the influence of the Pro12Ala genotype on body water and oedema formation, detected by ankle-foot volume assessed by water displacement, in patients with T2DM treated with TZD.
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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 | Yes |
E.6.5 | Efficacy | Yes |
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 | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
No camparator. Patient will be allocated to receive pioglitazone according to their genotype |
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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 | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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 | 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 | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |