E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
TYPE 2 DIABETES
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DIABETE DI TIPO 2 |
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E.1.1.1 | Medical condition in easily understood language |
TYPE 2 DIABETES |
DIABETE DI TIPO 2 |
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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 | 21.1 |
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 perform a clinical trial comparing DPP4i and glinides (linagliptin 5 mg once daily vs. repaglinide 0.5 mg thrice daily) on metabolic control, inflammatory and oxidative stress markers in older T2DM subjects using a metformin therapy diabetic patients. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the impact of DPP4i or glinides on physical and cognitive decline To evaluate the healthcare resource consumption |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• diagnosis of type 2 diabetes prior to informed consent • male and female patients who are pre-treated with an unchanged dose of immediate release metformin almost 4 weeks prior to randomization visit. Dose for metformin is defined as the maximum tolerated dose. • age >70 years or older • poor glycemic control (HbA1c >=7.5%) • risk of sarcopenia: low handgrip (men <= 30.0 kg, women <= 20.0 kg) or slow habitual walking speed (< 1m/s) • signed and dated written informed consent |
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E.4 | Principal exclusion criteria |
•diagnosis of type 1 diabetes mellitus •impaired kidney function (eGFR<30 ml/min per 1.73 m2) •active malignancy within 24 months prior to screening •heart failure NYHA III-IV, •use of GLP-1 agonists or DPP-IV therapy in the last 3 months. •history of pancreatitis; •hepatic disease (liver function tests more than 3 times the upper limit of normal); •chronic Obstructive Pulmonary Disease (COPD); •uncontrolled hypertension (BP > 160/100 mm of Hg); •known hypersensitivity to linagliptin and/or repaglinide or inactive ingredients •life expectancy less than 6 months; •diagnosis of dementia; •complete dependency in Basic Activities of Daily Living (BADL); •participation in any other clinical trial; •patients unwilling to provide consent and those who cannot be followed-up or unable to co-operate with the study procedures; •treatment with anti-obesity drugs, systemic corticosteroids or nonsteroidal anti-inflammatory drugs, any other anti-diabetic medication including insulin therapy (except metformin). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline after 24 weeks of treatment of in the inflammation composite score before and after linagliptin use as compared to repaglinide |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from baseline after 24 weeks of treatment |
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E.5.2 | Secondary end point(s) |
Change from baseline after 24 weeks of treatment of fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1C), markers of inflammation and oxidative stress (TNF-α, IL1β; IL6, IL18, nitrotyrosine), biological and molecular markers linked to diabetes (plasma and exosomal inflamma-miRs (Front Genet. 2013; 4: 121) such as Mir-21, Mir-126, Mir-146, Mir-181, AGE (advanced glycation endproducts), RAGE (receptor for advanced glycation endproducts), lean muscle mass (DEXA), incidence of major comorbidities, physical performance (SPPB), cognitive impairment (MMSE), risk of depression (GDS), malnutrition/undernutrition (MNA), health-related quality of life (EQ-5D), use of healthcare resources. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from baseline after 24 weeks 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 | 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 | 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 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |