Diastolic dysfunction in non-diabetic patients with metabolic syndrome
Conditions
Interventions
Trade Name: Metformin 500mg (Glucophage)
Pharmaceutical Form: Film-coated tablet
Trade Name: Metformin (1000mg) - Risidon
Pharmaceutical Form: Film-coated tablet
Sponsors
Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Non-diabetic adults aged between 40 and 64 years fulfilling the AHA/NHLBI criteria for clinical diagnosis of metabolic syndrome [(at least 3 of the following: waist circumference =102cm in males or =88cm in females; fasting plasma triglycerides =150mg/dL or on drug treatment for elevated triglycerides; fasting HDL cholesterol ?40mg/dL in males or ?50mg/dL in females or on drug treatment for reduced HDL; systolic blood pressure=130mmHg or diastolic blood pressure=85mmHg or on antihypertensive drug treatment in a patient with history of hypertension; fasting plasma glucose=100mg/dL)] AND WITH - Echocardiographic evidence of left ventricle diastolic dysfunction at rest, considering the mean of septal and lateral E’ as assessed by Tissue Doppler Imaging echocardiography (E’mean?10.2 cm/s if 40-59 years old or E’mean?7,2 cm/s if aged 60 to 65 years old). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Diagnosis of diabetes mellitus according to the ADA criteria (at least one of the following: fasting plasma glucose =126mg/dL; 2-hour plasma glucose =200mg/dL during an oral glucose tolerance test, as described the WHO; random plasma glucose =200mg/dL in a patient with classical symptoms of hyperglycemia or hyperglycemic crisis; hemoglobin A1C=6.5% using a method that is NGSP certified and standardized to the DCCT assay or =48mmol/mol reported in IFCC units) - Previous diagnosis of ischemic heart disease (history of angina, acute coronary syndrome, acute myocardial infarction or coronary artery bypass graft surgery); - Left ventricle ejection fraction less than 50% (assessed by transthoracic echocardiography); - Moderate or severe cardiac valvular disease; - Pericardial disease; - Uncontrolled atrial or ventricular tachyarrhythmias; - History of myocarditis; - Renal disease or dysfunction (plasma creatinine =1.5mg/dL in males or =1.4mg/dL in females); - Significant liver disease (aspartate aminotransferase or alanine aminotransferase =2.5 times upper limit of normal); - Females who are pregnant, planning to become pregnant or who admit sexual activity without appropriate contraception; - Lactation. - Unable to perform cardopulmonary exercise test. - Recent (less than 1 month) change in anti-hypertensive or antidislipidemic medications.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate if treating non-diabetic patients with metabolic syndrome (MS) and rest diastolic dysfunction (DD) with metformin, in addition to a lifestyle change intervention program, improves diastolic function and assess its impact in functional capacity and health-related quality of life. ;Secondary Objective: - To evaluate if biomarkers of cardiac remodeling, inflammation, and glucose homeostasis are predictive factors of response to metformin treatment of non-diabetic patients with MS and DD.;Primary end point(s): Change in mean of septal and lateral early diastolic mitral annular velocities (E’) during the 24 month follow-up period. ;Timepoint(s) of evaluation of this end point: Serial echocardiographic measurements will be performed at baseline, month 6, month 12 and month 24 after randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in diastolic echocardiographic parameters: E/E´ratio, isovolumetric relaxation time (IVRT), E/A ratio, E wave deceleration time (DT), diastolic dysfunction grades according to the ASE/ESE consensus, strain rate during IVRT (SR-IVR) and E/SR-IVR ratio; - Change in metabolic parameters: insulin and glucose plasma levels, insulin resistance (HOMA – Homeostasis Model Assessment) and adiponectin levels. - Change in cardiovascular biomarkers: NTproBNP and high sensitivity C-reactive protein; - Change in remodeling and inflammation biomarkers: TNFa, TIMP1 e GDF-15; - Change in functional capacity during cardiopulmonary exercise test, including assessment of peak oxygen uptake, anaerobic threshold and ventilatory efficiency; - Change in epicardial, pericardial and abdominal adipose tissue volumes, and coronary calcium score, assessed by cardiac multidetector CT (MDCT) - Change in health-related quality of life, according to Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36).;Timepoint(s) of evaluation of this end point: Blood sampling: baseline, months 12 and 24 Echocardiography: baseline, months 6, 12 and 24 Cardiac CT: baseline, month 24 Cardiopulmonary exercise test: baseline, months 12 and 24 SF-36: baseline, months 12 and 24 | — |
Countries
Portugal
Contacts
Public ContactDepartment of Physiology
Faculty of Medice, University of Porto
Outcome results
None listed