E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metabolic syndrome |
sindrome metabolica |
|
E.1.1.1 | Medical condition in easily understood language |
Metabolic syndrome, characterized by abdominal obesity, hypertension, high plasma glucose, high triglycerides, and low HDL cholesterol |
sindrome metabolica, caratterizzata da obesità addominale, ipertensione, glicemia alta, trigliceridi alti, e basso livello di colesterolo buono (HDL) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 |
The aim of the study is to evaluate the effect of a comprehensive life-style intervention (including moderate physical activity and Mediterranean/macrobiotic diet with moderate calorie and protein restriction), and of treatment with Metformin (a calorie restriction mimetic drug) for the prevention of age-related chronic diseases |
L’obiettivo dello studio è di valutare gli effetti di un intervento volto a far cambiare lo stile di vita (con un programma comprendente moderata attività fisica e dieta Mediterranea/macrobiotica per ottenere una moderata restrizione calorica e proteica), e o di un trattamento con metformina (un farmaco mimetico di restrizione calorica) sulla prevenzione delle patologie croniche legate all’età. |
|
E.2.2 | Secondary objectives of the trial |
Evaluate the effect of the intervention on total mortality and on the incidence of specific chronic diseases (diabetes, myocardial infarction, stroke, cancers, and others). |
Valutare l’impatto dell’intervento sulla mortalità totale e sull’incidenza di specifiche patologie croniche (diabete, infarto cardiaco, ictus cerebrale, tumori e altre) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 55-74, waist circumference equal or greater than 85 cm for women and 100 cm for men, plus at least two other factors among those defining the metabolic syndrome. |
Età 55-74, circonferenza vita maggiore o uguale a 85 cm per le donne e 100 cm per gli uomini, più almeno altri due fattori fra quelli che definiscono la sindrome metabolica |
|
E.4 | Principal exclusion criteria |
-Dignosed diabetes (or baseline fasting glycemia above 7 mmol/L) at baseline examination - cancer (except skin carcinoma) diagnosed in the last 5 years, or under treatment. -Excessive frailty: in absence of agreed-upon measurements parameters and cutoff points, we will exclude subjects under the lower 5th percentile of the muscular mass distribution estimated by impedance in previous studies. - Conditions that controindicate the use of MET because may favour lactic acidosis: Renal, cardiac, hepatic, or respiratory insufficiency, serum creatinine > 124 µmol/L, or proteinuria. Curent treatment with K-sparing diuretics, or with proton pump inhibitors. Excessive alcohol consumption. -Distressing side effects of MET treatment, such as nausea and diarrhoea. |
- Diagnosi di diabete (o glicemia basale a digiuno superiore a 7mmol/L)
-diagnosi di cancro (eccetto epiteliomi cutanei) negli ultimi 5 anni o in corso di trattamento
- eccessiva debolezza, con massa magra impedenziometrica inferiore al 5° percentile
- Condizioni che controindicano l’uso di metformina in quanto potrebbero favorire l’acidosi lattica: insufficienza renale, cardiaca, epatica o respiratoria. Creatinina sierica >124 µmol/L, o proteinuria. Trattamento con diuretici risparmiatori di potassio o con inibitori della pompa protonica. Eccessivo consumo di alcol
- Effetti collaterali fastidiosi della metformina tipo nausea e/o diarrea
|
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E.5 End points |
E.5.1 | Primary end point(s) |
Total incidence of age related chronic diseases. We will retrieve records for all Age related chronic diseases but we will first concentrate the analysis on cancer, coronary heart disease, stroke, and diabetes |
Incidenza complessiva di malattie croniche legate all’età. Registreremo l’incidenza di tutte le patologie ma ci concentreremo prioritariamente su diabete, malattie cardiovascolari, tumori maligni. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Total mortality and incidence of specific chronic diseases |
Mortalità totale e incidenza di specifiche malattie croniche |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
A longer follow-up, of the order of 8-10 years will be necessary to analyse the incidence of specific chronic diseases |
Una sufficiente potenza statistica per esaminare specifiche patologie richiederà un follow-up più prolungato, dell'ordine di 8-10 anni. |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
prevention of age related chronic diseases. |
prevenzione delle malattie croniche legate all'età. |
|
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 | Yes |
E.8.1.7.1 | Other trial design description |
disegno fattoriale con metformina versus placebo in doppio cieco e dieta e attività fisica in aperto |
factorial randomization by metformin/placebo, diet physical activity/not diet Physical activity |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
dieta versus raccomandazioni |
Diet versus recommendations |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |