Prevention of Microvascular Complications in Prediabetes e-PREDICE Study

Early Prevention of Diabetes Complications in People With Hyperglycaemia in Europe: e-PREDICE Study

Sponsors

Lead Sponsor: Evidem Consultores SL

Collaborator: European Commission
Boehringer Ingelheim
Merck Serono International SA

Source Evidem Consultores SL
Brief Summary

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.

Overall Status Unknown status
Start Date 2015-03-15
Completion Date 2019-12-31
Primary Completion Date 2018-12-31
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Microvascular Complication Index "MIC" : 2-year
Diabetic Retinopathy: Scale ETDRS 2-year
Urine albumin to creatinine ratio (UACR) 2-year
Sudomotor Index 2-year
Secondary Outcome
Measure Time Frame
incidence of diabetes 2-year
endothelial dysfunction 2-year
Insulin sensitivity 2-year
Inflammation biomarkers 2-years
NAFLD biomarkers 2-year
Quality of life 2-year
cognitive function 2-year
depressive symptoms 2-year
Enrollment 1000
Condition
Intervention

Intervention Type: Drug

Intervention Name: Placebo, metformin, linagliptin, linagliptin + metformin

Eligibility

Criteria:

Inclusion criteria - Impaired Fasting Glucose (IFG): Fasting Plasma Glucose (FPG) 6.1 to 6.9mmol/l and 2-hour Plasma Glucose (2-h PG): <7.8mmol/L; - Impaired Glucose Tolerance (IGT): FPG <7.0mmol/L and 2h PG >_7.8 and <11.1 mmol/L -Informed consent given Exclusion Criteria: - Type 1 diabetes (T1D) - known or screen-detected Type 2 diabetes (T2D). - Use of any anti-diabetic drug within the 3 months prior to inclusion. - Previous cardiovascular event, stroke or revascularization procedure of any arterial territory - Morbid obesity (BMI>45) - Current renal replacement therapy. - Renal function impairment: GFR <60 ml/min/1.73m2. - Previous diagnosis of liver cirrhosis or chronic hepatitis - Elevation of liver enzymes (AST/AST) >3 times of the upper normal ranges** (6m or BL). - Previous diagnosis of acute or chronic pancreatitis - Elevation of pancreatic enzymes (Amylase/Lipase) >3 times of the upper normal ranges (6m or BL). - Previous diagnosis of Chronic Heart Failure (NYHA class III or higher). - Organ transplant or waiting for organ transplant. - Diagnosis of malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years. - End-stage or metastatic cancer. - Known or suspected hypersensitivity to trial products or related products. - Known use of non prescribed narcotics or illicit drugs. - Simultaneous participation in any other clinical trial of an investigational agent. - Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant. - Cataract that impedes the retinal evaluation of both eyes. - Ocular surgery planned in the next 6 months - Concomitant intraocular treatment (retina or choroid). - Tropicamide allergy - Participants with screen retinogram not optimal for retinal assessment - Complete amputation of one/ both hands or one/both feet. - Dementia, mental disorder or evident cognitive impairment unable to give informed consent. - Institutionalization (nursing/mental health home, hospital, prison, etc). - Suspected renal artery stenosis Recent gastrointestinal bleeding (within the last year) - Any circumstance where ongoing medication might lead to potential adverse drug effect. - Any other acute condition or exacerbation of chronic condition that in the investigator's opinion would interfere with the trial initiation or visit schedules or procedures.

Gender:

All

Minimum Age:

45 Years

Maximum Age:

74 Years

Healthy Volunteers:

No

Overall Official
Overall Contact Contact information is only displayed when the study is recruiting subjects.
Location
Facility: Status: Contact: Contact Backup: Centro de Salud Jose Marva Esther Sanchez, MD +34629
Location Countries

Spain

Verification Date

2017-06-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Placebo

Type: Placebo Comparator

Description: Placebo Lifestyle modification (diet and physical activity recommendations)

Label: Metformin

Type: Experimental

Description: Metformin Lifestyle modification (diet and physical activity recommendations)

Label: Linagliptin

Type: Experimental

Description: Linagliptin Lifestyle modification (diet and physical activity recommendations)

Label: Linagliptin and Metformin

Type: Experimental

Description: Fixed dose combination of Linagliptin and metformin Lifestyle modification (diet and physical activity recommendations)

Acronym ePREDICE
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: Randomized, parallel , single-blind, placebo controlled

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description: Two groups (linagliptin vs placebo) double-blind Two groups (metformin & metformin+linagliptin) single-blind

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