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Content archived on 2024-06-18

Early Prevention of Diabetes Complications in people with Hyperglycaemia in Europe

Objective

"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."

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Programme(s)

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Topic(s)

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FP7-HEALTH-2011-two-stage
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Funding Scheme

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CP-FP - Small or medium-scale focused research project

Coordinator

EVIDEM CONSULTORES SL
EU contribution
€ 1 721 679,68
Address
CALLE MARROQUINA 12 PLANTA 1 PUERTA A
28030 MADRID
Spain

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

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Participants (35)

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