Non diabetic hyperglycaemia: Impaired Glucose Tolerance (IGT) or Impaired Fasting Glucose (IFG) or both MedDRA version: 20.0 Level: LLT Classification code 10065542 Term: Prediabetes System Organ Class: 100000004861
Conditions
Sponsors
EVIDEM CONSULTORES SL (EVIDEM)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Men and women • Age 45 -74 years • Impaired Fasting Glucose (IFG): FPG 6.1 to 6.9mmol/l and 2-h PG _7.8 and =65 years) yes F.1.3.1 Number of subjects for this age range 500
Exclusion criteria
Exclusion criteria: • Type 1 diabetes. • Known* or unknown T2D (including screen detected T2D) with or without pharmacological treatment. • Use of a GLP-1 receptor agonist (exenatide or other) or pramlintide or any dipeptidyl peptidase 4 (DPP-4) inhibitor or metformin within the 3 months prior to enrolment. • Use of insulin or long-acting insulin analogue within 3 months prior to enrolment. • Any previous cardiovascular or cerebrovascular clinically documented event or revascularization procedure*. • Clinical evidence of macro-vascular complications (overt clinical cardiovascular disease) at enrolment, including angina (stable or unstable) and evidence of previous myocardial infarction in baseline EKG. • Current renal replacement therapy. • A previous diagnosis of liver cirrhosis or chronic hepatitis*, or an elevation of liver enzymes (AST and or ALT) >3 tiems normal ranges. • Previous diagnosis of Chronic heart failure (NYHA class III or higher). • A prior solid organ transplant or awaiting solid organ transplant. • Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years. Subjects with intraepithelial squamous cell carcinoma of the skin (Bowen’s disease) treated with topical 5-fluorouracil (5FU) and subjects with basal cell skin cancer are allowed to enter the trial. • Any acute condition or exacerbation of chronic condition that would in the Investigator's opinion interfere with the initial trial visit schedule and procedures. • 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 (all fertile women will be tested for before randomization), breast-feeding or intend to become pregnant. • Presence of cataract that impedes the retinal evaluation of both eyes. • Other previously diagnosed retinal diseases. • Any diseases that would prevent the measurement of primary endpoints • Dementia, mental disorder or evident cognitive impairment unable to give informed consent. • End-stage or metastatic cancer. • Institutionalization. • Renal function impairment: GFR 3 times the upper limit of normal, history of cirrhosis or hepatitis, suspected renal artery stenosis, recent gastrointestinal bleeding (within the last year), pregnant, breastfeeding or a female of child-bearing potential not on reliable contraception and also any circumstance where ongoing medication might lead to potential adverse drug interaction with components of the trial medications. • Any other reason, medical condition, ongoing medication or significant disability that would prevent the participant complying with trial consent, treatment and follow-up procedures or potentially jeopardise her/his medical care. * Previous diagnosis should be documented after medical record review.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of treatment with linagliptin, metformin or the combination of linagliptin with metformin, plus lifestyle intervention (diet and physical activity), compared to lifestyle intervention alone, for at least 2 years, and up to 4 years, on different microvascular parameters (retinal, renal and neurological), as defined by the primary and secondary endpoints, in adults with non diabetic hyperglycaemia (IGT, IFG or IFG plus IGT).;Secondary Objective: 1- To identify among people with hyperglycaemia who are most likely to develop early diabetic complication 2- To determine the extent to which the compliance to the interventions affect the rate on early diabetic complications prevention 3- To evaluate the effect of the different treatment regimes applied in this study on quality of life and neuropsychological functions 4- To assess the efficacy of treatment with linagliptin, metformin and the combination of sitagliptin with metformin plus lifestyle intervention in comparison to lifestyle intervention alone with regard to surrogate parameters of vascular function and structure, and novel biomarkers of microvascular damage in adults with hyperglycaemia (IGT, IFG or IFG plus IGT) 5- To determine the safety of linagliptin or metformin and the combination of sitagliptin with metformin plus lifestyle intervention in people with non diabetic hyperglycaemia with regard to severe adverse effects and clinically important events ;Primary end point(s): The primary endpoint is a combined continuous variable, "the microvascular complication índex" (MCI), composed by the linear combination of the Early Treatment Diabetic Retinopathy Study Scale (ETDRS) score, the level of urinary albumin to creatinine ratio, and sudomotor test (SUDOSCAN) score, measured during the 24th and 36th month visits.;Timepoint(s) of evaluation of this end point: 24 and 36months after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Retinopathy score at last visit defined as 2 steps progression on the ETDRS scale between baseline and visits at months 24th and 36h . • One standard deviation (SD) increase on the level of urinary albumin to creatinine ratio between baseline and visits at months 24th and 36h . • One SD decrease Changes in the level of hands and feet conductance in SUDOSCAN between baseline and visits at months 24th and 36h . • Change in microvascular endothelial function (MEF) measured by the EndoPAT method (in a subset). • Change in the Non-Alcoholic Fatty Liver (NAFL) Index (in a subset). • Change in biomarkers of microvascular damage, endothelial function, per-oxidation, inflammation, and metabolomics (in a subset). • Change in the insulin secretion and ß-cell function. • Change in self-perceived Quality of Life (QoL). • Change in symptoms of peripheral neuropathy • Change in neuropsychological parameters: cognitive function, anxiety and depressive symptoms and indices. • Changes in Obstructive Sleep Apnoea (OSA) indices as measured by Somnomedics (in a subset). • Changes in ambulatory blood pressure monitoring (in a subset) • Change in the mean common carotid intimae-media thickness (CIMT) (in a subset). • Incidence of major cardiovascular events, defined as an expanded composite of total coronary events, total stroke events, revascularization procedures (coronary artery bypass graft, percutaneous coronary angioplasty, and peripheral revascularization), hospitalization for heart failure, transient ischaemic attack, and cardiovascular or cerebrovascular death ;Timepoint(s) of evaluation of this end point: 24 and 36 months. | — |
Countries
Australia, Austria, Bulgaria, Greece, Italy, Lithuania, Poland, Serbia, Spain, Turkey
Contacts
Public ContactKatedra i Klinika Endokrynologii UJ
Dr Aleksandra-Gilis Januszewska
Outcome results
None listed