E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
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 |
To evaluate if Ursodeoxycholic acid reduces albuminuria in patients with type 1 diabetes mellitus (T1DM) with residual albuminuria despite established standard care. |
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E.2.2 | Secondary objectives of the trial |
To evaluate if Ursodeoxycholic acid improves n vascular , metabolic and renal measures / function excretion
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- T1DM patients aged 20 to 75 years, with residual albuminuria (defined as an urine albumin to creatinine ratio >3 mg/mmol) or proteinuria in the preceding 6 months on a maximum tolerated and stable dose of RAAS blockade (ACE-inhibitor or angiotensin receptor blocker-ARB).
- Estimated GFR (by MDRD equation) ≥30 ml/min.
- Written informed consent to participate in the study prior to any study procedures.
- Ability to communicate and comply with all study requirements.
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E.4 | Principal exclusion criteria |
- History of intolerance to Ursodeoxycholic acid.
- Active gastrointestinal disease (such as gall stones, inflammatory bowel disease, primary sclerosing cholangitis).
- Non-diabetic renal disease.
- Absence of diabetic retinopathy (as this would suggest non diabetic renal disease).
- Pregnancy.
- Insufficient understanding of the trial
- Lactating females
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in albumin excretion rate (AER) after 24 weeks treatment with Ursodeoxycholic acid as compared to 24 weeks on placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Change in endothelial function and permeability Change in serum electrolytes (sodium, potassium), and renal function/estimated GFR
Change in brachial blood pressure.
Change in central aortic blood pressure and Ao-PWV.
Change in HbA1c, lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides).
Change in plasma albumin and liver function tests (ALT, ALP GGT).
Change in 24 hours urine sodium, urine magnesium, uric acid, calcium and phosphate, potassium
excretion.
Change in endothelial and renal injury markers; hsCRP, VCAM, ET-1, vWF, oxLDL, Interleukin 6,
Interleukin 1-beta, Interleukin 18, NGAL, KIM-1 and LFABP.
Change in levels of circulating serum levels of Ursodeoxycholic acid and other bile acids (including cholic acid,deoxycholicacid, chenodeoxycholic acid, lithocholic acid)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | No |
E.8.1.6 | Cross over | Yes |
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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |