NCT03222765: ePREDICE

Prevention of Microvascular Complications in Prediabetes e-PREDICE Study

Status unknown NA Last updated 19 July 2017

What this trial tests

NA trial testing Placebo, metformin, linagliptin, linagliptin + metformin in PreDiabetes in 1,000 participants. Status unknown.

Timeline

15 March 2015

Primary endpoint
31 December 2018

31 December 2019

Quick facts

Lead sponsor	Evidem Consultores SL
Phase	NA
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	1,000
Start date	15 March 2015
Primary completion	31 December 2018
Estimated completion	31 December 2019
Sites	1 location across Spain

Drugs / interventions tested

• Placebo, metformin, linagliptin, linagliptin + metformin — full drug profile →

Conditions studied

• PreDiabetes — all drugs for PreDiabetes →

Sponsor

Evidem Consultores SL — full company profile →

Who can join

Adults 45 to 74, any sex, with PreDiabetes. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

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 14 clinical centres from 10 countries: Australia, Austria, Bulgaria, Greece, Italy, Kuwait, Poland, Serbia, Spain and Turkey and . (N=1000)

Main Outcomes: The primary endpoint is a combined continous 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, serological biomarkers of inflammation, vascular damage, non-alcoholic fatty liver disease, insulin secretion, measures of quality of life, sleep quality, neuropsychological evaluation and endothelial function will be also evaluated in a subset of participants.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus.
   Madsen KS, Chi Y, Metzendorf MI, Richter B, et al · · 2019 · cited 35× · PMID 31794067 · DOI 10.1002/14651858.cd008558.pub2
2. Prevention and Management Strategies for Diabetic Neuropathy.
   Smith S, Normahani P, Lane T, Hohenschurz-Schmidt D, et al · · 2022 · cited 34× · PMID 36013364 · DOI 10.3390/life12081185
3. Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data.
   Gabriel R, Boukichou Abdelkader N, Acosta T, Gilis-Januszewska A, et al · · 2020 · cited 32× · PMID 32282852 · DOI 10.1371/journal.pone.0231196
4. Effect of metformin on microvascular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.
   Gerardo González-González J, Cesar Solis R, Díaz González-Colmenero A, Raygoza-Cortez K, et al · · 2022 · cited 8× · PMID 35247521 · DOI 10.1016/j.diabres.2022.109821
5. Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.
   Gabriel R, Boukichou-Abdelkader N, Gilis-Januszewska A, Makrilakis K, et al · · 2023 · cited 4× · PMID 36902821 · DOI 10.3390/jcm12052035
6. Prevalence and factors linked to renal involvement in prediabetes patients across Europe in the ePREDICE trial.
   Mas-Fontao S, Civantos E, Boukichou N, Moreno JA, et al · · 2024 · cited 1× · PMID 39638835 · DOI 10.1038/s41598-024-79842-w