Objectif
"Background: A significant proportion of pre-diabetics, show macro and micro vascular complications associated with hyperglycaemia. Although many trials have demonstrated the efficacy of lifestyle and pharmaceutical interventions in diabetes prevention, no trial has evaluated the extent to which mid- and long-term complications can be prevented by early interventions on hyperglycaemia.
Aims: To assess the long-term effects on multiple complications of hyperglycaemia of early intensive management of hyperglycaemia with linagliptin, metformin or their combination added to lifestyle intervention (LSI) (diet and physical activity), compared with LSI alone in adults with non-diabetic intermediate hyperglycaemia (IFG, IGT or both).
Study Design: Investigator initiated (non-commercial), long-term, multi-centre, randomised, partially double blinded, placebo controlled, phase-IIIb clinical trial with prospective blinded outcome evaluation. Participants will be randomised to four parallel arms: 1) LSI + 2 placebo tablets/day; 2) LSI + 2 Metformin tablets of 850 mg/day; 3) LSI + 1 Linagliptin tablets of 5 mg/day and 1 placebo; 4) LSI + 2 tablets of a fixed-dose combination of Linagliptin 2.5mg and Metformin 850 /day. Active intervention will last for at least 2 years, and additional follow-up up to 4 years.
Setting and population: Males and Females with pre-diabetes (IFG, IGT or both) aged 45 to 74 years selected from primary care screening programs in 15 clinical centres from 12 countries. (N=2000).
Main Outcomes: The primary endpoint is a combined continuous variable: “the microvascular complication índex"" (MCI) composed by a linear combination of the Early Treatment Diabetic Retinopathy Study Scale (ETDRS) score (based on retinograms), the level of urinary albumin to creatinine ratio, and a measure of distal small fibre neuropathy (sudomotor test by SUDOSCAN), measured during baseline visit and at 24th and 48th month visits after randomisation. In addition, this project will include the evaluation of early novel serological biomarkers of systemic inflammation, early micro-vascular damage, non-alcoholic fatty liver disease, insulin sensitivity and insulin secretion, and measures of quality of life, sleep quality (somnograms) and neuropsychological evaluation. Vascular function and structure will be evaluated in a subset of participants (n=1000), including cIMT and microvascular endothelial function measured by EndoPAT.
Expected results: By evaluating the effect of aggressive treatments in pre-diabetes for the early prevention of diabetes complication, this project has the potential of changing the current paradigm of early management of hyperglycaemia. The ultimate goal is the development of a standardized core protocol for the early prevention of microvascular and other complications, impacting social cost as a result not only in health care, but also in disabilities at work."
Champ scientifique
Appel à propositions
FP7-HEALTH-2011-two-stage
Voir d’autres projets de cet appel
Régime de financement
CP-FP - Small or medium-scale focused research projectCoordinateur
28030 MADRID
Espagne
Voir sur la carte
Participants (35)
Participation terminée
28046 MADRID
Voir sur la carte
00271 Helsinki
Voir sur la carte
Participation terminée
28040 MADRID
Voir sur la carte
56126 Pisa
Voir sur la carte
47002 VALLADOLID
Voir sur la carte
3500 Krems
Voir sur la carte
462 80 Vanersborg
Voir sur la carte
Participation terminée
28010 MADRID
Voir sur la carte
01069 Dresden
Voir sur la carte
1090 Bruxelles / Brussel
Voir sur la carte
00185 Roma
Voir sur la carte
Participation terminée
5020 Salzburg
Voir sur la carte
Participation terminée
44307 Kaunas
Voir sur la carte
10561 Athina
Voir sur la carte
08007 Barcelona
Voir sur la carte
08035 Barcelona
Voir sur la carte
34452 Istanbul
Voir sur la carte
Participation terminée
11000 BEOGRAD
Voir sur la carte
11000 Belgrade
Voir sur la carte
31007 KRAKOW
Voir sur la carte
2006 Sydney
Voir sur la carte
1431 SOFIA
Voir sur la carte
00014 Helsingin Yliopisto
Voir sur la carte
47011 VALLADOLID
Voir sur la carte
Participation terminée
66030 SANTA MARIA IMBARO
Voir sur la carte
28002 MADRID
Voir sur la carte
1950 Sion
Voir sur la carte
Participation terminée
1211 Geneve
Voir sur la carte
75014 PARIS
Voir sur la carte
70600 KUOPIO
Voir sur la carte
E1 4NS London
Voir sur la carte
5020 Salzburg
Voir sur la carte
28040 Madrid
Voir sur la carte
41071 Sevilla
Voir sur la carte
11000 BEOGRAD
Voir sur la carte