Obesity and Metabolic Syndrome (combination of obesity, hypertension, raised blood glucose and cholesterol abnormalities) MedDRA version: 13.1 Level: PT Classification code 10052066 Term: Metabolic syndrome System Organ Class: 10027433 - Metabolism and nutrition disorders MedDRA version: 13.1 Level: PT Classification code 10029883 Term: Obesity System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Inspra (Eplerenone)
Product Name: Eplerenone (Inspra)
Product Code: 0025-1710
Pharmaceutical Form: Film-coated tablet
Sponsors
Central Manchester Foundation Hospitals Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • • Participants will have obesity: Waist girth > 102cm (40 inches) in men or > 94cm (37 inches) in women • In addition participants will have 3 or more components of the metabolic syndrome o Fasting plasma glucose = 6.1mmol/L o Serum triglycerides = 1.7mmolL o Serum High Density Lipoprotein (HDL) cholesterol 130/85mmHg or treated blood pressure • Participants will be aged between 30 and 65 years of age • Patients with normal platelet count (150-400 x 109 per litre). 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Pregnant / lactating mothers • Diagnosed diabetes mellitus • Hypersensitivity to eplerenone or any of the excipients • Patients with serum potassium level > 5.5 mmol/L at initiation • Patients with moderate to severe renal insufficiency (creatinine clearance < 50 mL/min) • Patients with severe hepatic insufficiency (Child-Pugh Class C) • Patients taking a-blockers for hypertension • Patients receiving potassium-sparing diuretics or potassium-supplements • Patients taking strong inhibitors of CYP 3A4 (eg itraconazole, ketoconazole, ritonavir, nelfinavir, clarithromycin, telithromycin and nefazodone) • Patients taking: Lithium, Tricyclic anti-depressants, neuroleptics, amifostine, baclofene : Co-administration of these drugs with eplerenone may potentially increase antihypertensive effects and risk of postural hypotension • Patients taking Cyclosporin or tacrolimus: Cyclosporin and tacromilus may lead to impaired renal function and increase the risk of hyperkalaemia. • Patients taking Trimethroprim: The concomitant administration of trimethroprim with eplerenone increases the risk of hyperkalaemia. • Patients taking Digoxin: Systemic exposure (AUC) to digoxin increases by 16% (90% CI: 4% - 30%) when co-administered with eplerenone. • Co-administration of St John's Wort (a strong CYP3A4 inducer) with eplerenone caused a 30 % decrease in eplerenone AUC. • Galactose intolerance or lactase deficiency (due to composition of tablet) • Systolic Blood pressure below 120mmHg
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: This research project asks the question: "Can the drug Eplerenone improve blood vessel function in overweight patients" Being overweight (or in medical terms 'obesity') causes very severe damage to all the blood vessels in the body, both in terms of their structure and their function. This damage is associated with the development of high blood pressure, stroke disease and heart attacks. One of the reasons that obesity causes damage to blood vessels is that a process known as inflammation (a similar reaction to being stung by a nettle - your skin swells, is painful and becomes red) occurs in fat cells. These fat cells surround blood vessels and the inflammation then causes abnormalities to the vessel function. Eventually, structural damage occurs also. In our laboratory, we have recently seen that the drug Eplerenone is able to reduce inflammation in fat cells which is associated with obesity. As such we suspect that it will also improve blood vessel function. Eplerenone is a wel;Secondary Objective: Secondary Objectives: To determine whether treatment with Eplerenone in patients with obesity and metabolic syndrome is able to improve: 1) Basal Metabolic rate 2) Insulin resistance (HOMA-IR) and Insulin sensitivity (HOMA-B) 3) Bio-impedance (measure of total body fat content) 4) Circulating fat hormone (adipocytokine)levels: adiponectin and leptin levels 5) Markers of systemic inflammation (highly sensitive CRP) and IL-6 (a surrogate measure of adipose tissue inflammation in obesity) 6) Markers of diastolic dysfunction (early heart failure);Primary end point(s): To determine whether Eplerenone is able to statistically significantly improve the effect of perivascular adipose tissue (PVAT) on the function of subcutaneous small arteries taken from patients with obesity and metabolic syndrome. | — |
Countries
United Kingdom
Outcome results
None listed