Effects of aldosterone antagonism on microvascular function in obese individuals

Completed

• Conditions: hypertension/high blood pressure; insulin resistance/decreased sensitivity for insulin; 10018424; 10057166

• Registration Number: NL-OMON45212
• Lead Sponsor: niversiteit Maastricht

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 60

Inclusion Criteria

- Age 40-65 years
- Caucasian (because of ethnic differences in microvascular function, vascular stiffness, and the prevalence of cardiovascular disease and associated risk factors)
- Waist circumference > 102 cm (men)/> 88 cm (women)
- High-normal blood pressure (office blood pressure: 130/85 * 139/89 mm Hg) or stage I/II hypertension (office blood pressure: 140/90 mm Hg * 179/109 mm Hg; 24h ABPM: 125/80 * 169/99 mm Hg)

Exclusion Criteria

- Cardiovascular disease (stroke, coronary artery disease, peripheral vascular disease, congestive heart failure, cardiac shunts, cardiac surgery, pulmonary hypertension, cardiac arrhythmias, family history of cardiac arrhythmias or sudden cardiac death)
- Diabetes mellitus/impaired fasting glucose (fasting glucose values > 6.1 mmol/L), because not only diabetes, but also intermediate hyperglycaemia has been associated with microvascular disease, which impedes the distinction between cause and consequence of disturbances in glucose metabolism in the concerning individuals
- Grade 3 hypertension (office blood pressure: > 180/110 mm Hg; ABPM > 170/100 mm Hg) in order not to expose these individuals to unnecessary risks by interrupting or postponing antihypertensive treatment
- Unstable or severe pulmonary disease
- Unstable or severe thyroid disorders
- Inflammatory diseases
- Alcohol use > 2 U/day (women)/> 3 U/day (men)
- Use of glucose-lowering medications, because of possible interference with microvascular function
- Use of corticosteroids (have also affinity for the mineralocorticoid receptor; can decrease the antihypertensive effect of Eplerenone), medication known to inhibit or induce CYP3A4 (possible interference with metabolism of Eplerenone), lithium (possible reduction of lithium excretion when used simultaneously with Eplerenone) , and tricyclic antidepressants or antipsychotic medication (risk of orthostatic hypotension when used simultaneously with Eplerenone), and regular use (weekly or several times a week) of NSAIDs (risk of acute renal dysfunction and disturbance of electrolyte excretion when used simultaneously with Eplerenone)
- Plasma potassium levels < 3.2 mmol/L or > 5 mmol/L
- eGFR < 60 mL/min
- Impairment of hepatic function
- Pregnancy or lactation

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoints are capillary recruitment during hyperinsulinemia in skeletal<br /><br>muscle, and insulin sensitivity. They will be related to plasma aldosterone<br /><br>concentration and compared before and after treatment with a mineralocorticoid<br /><br>receptor antagonist.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary endpoints are differences in other (micro)vascular measurements<br /><br>(baseline capillary density, skin capillary recruitment, skin vasomotion (basal<br /><br>and during local heating), endothelial glycocalyx thickness, carotid<br /><br>distensibility, augmentation index, carotid-femoral pulse wave velocity, and<br /><br>reactive hyperemia index), and biomarkers representing endothelial activation<br /><br>and low-grade inflammation, between fasting and hyperinsulinemic states. They<br /><br>will also be related to plasma aldosterone concentration, and compared before<br /><br>and after treatment with a mineralocorticoid receptor antagonist. </p><br>