Prevention of Microvascular Complications in Prediabetes e-PREDICE Study

NCT03222765 | Unknown DMC

• 1 other identifier: EU-FP7 279074
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

PreDiabetes

Keywords

prediabetes lifestyle drugs microvascular complications

Outcome Measures

Primary Outcomes (4)

• Microvascular Complication Index "MIC" :

  linear combination of three continous variables: ETRSD score, UACR and sudomotor index

  2-year

• Diabetic Retinopathy: Scale ETDRS

  ETDRS Score

  2-year

• Urine albumin to creatinine ratio (UACR)

  Ratio albumin to creatinine in mg/dl

  2-year

• Sudomotor Index

  SUDOSCAN sweat function

  2-year

Secondary Outcomes (8)

• incidence of diabetes

  2-year

• endothelial dysfunction

  2-year

• Insulin sensitivity

  2-year

• Inflammation biomarkers

  2-years

• NAFLD biomarkers

  2-year

Study Arms (4)

Placebo

PLACEBO COMPARATOR

* Placebo * Lifestyle modification (diet and physical activity recommendations)

Drug: Placebo, metformin, linagliptin, linagliptin + metformin

Metformin

EXPERIMENTAL

* Metformin * Lifestyle modification (diet and physical activity recommendations)

Drug: Placebo, metformin, linagliptin, linagliptin + metformin

Linagliptin

EXPERIMENTAL

* Linagliptin * Lifestyle modification (diet and physical activity recommendations)

Drug: Placebo, metformin, linagliptin, linagliptin + metformin

Linagliptin and Metformin

EXPERIMENTAL

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

Drug: Placebo, metformin, linagliptin, linagliptin + metformin

Interventions

Placebo, metformin, linagliptin, linagliptin + metformin DRUG

Linagliptin; Linagliptin and Metformin; Metformin; Placebo

Eligibility Criteria

• Age: 45 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Type 1 diabetes (T1D)
• known or screen-detected Type 2 diabetes (T2D).
• 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.

Sponsors & Collaborators

• Evidem Consultores SL: lead
• European Commission: collaborator
• Boehringer Ingelheim: collaborator
• Merck Serono International SA: collaborator

Study Sites (1)

Centro de Salud Jose Marva

Madrid, 28030, Spain

RECRUITING

Related Publications (2)

• El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.

  PMID: 38837240 DERIVED

• Gabriel R, Boukichou Abdelkader N, Acosta T, Gilis-Januszewska A, Gomez-Huelgas R, Makrilakis K, Kamenov Z, Paulweber B, Satman I, Djordjevic P, Alkandari A, Mitrakou A, Lalic N, Colagiuri S, Lindstrom J, Egido J, Natali A, Pastor JC, Teuschl Y, Lind M, Silva L, Lopez-Ridaura R, Tuomilehto J; e-PREDICE Consortium. Early prevention of diabetes microvascular complications in people with hyperglycaemia in Europe. ePREDICE randomized trial. Study protocol, recruitment and selected baseline data. PLoS One. 2020 Apr 13;15(4):e0231196. doi: 10.1371/journal.pone.0231196. eCollection 2020.

  PMID: 32282852 DERIVED

Related Links

• Webpage ePREDICE Project

MeSH Terms

Conditions

Prediabetic State

Interventions

Metformin; Linagliptin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Study Officials

• Rafael Gabriel, MD, PhD

  Evidem Consultores SL

  PRINCIPAL INVESTIGATOR

• Jaakko Tuomilehto, MD, PhD

  Evidem Consultores SL

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nisa Boukichou, Ms

CONTACT

+34914025066; nisa@ceiis.org

Margarita Alonso, MS

CONTACT

+34914025066; mgalonso@ceiis.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Two groups (linagliptin vs placebo) double-blind Two groups (metformin \& metformin+linagliptin) single-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, parallel , single-blind, placebo controlled

Study Record Dates

• First Submitted: June 20, 2017
• First Posted: July 19, 2017
• Study Start: March 15, 2015
• Primary Completion: December 31, 2018
• Study Completion: December 31, 2019
• Last Updated: July 19, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)