Aldosterone Antagonism and Microvascular Function

NCT ID: NCT01887119

Last Updated: 2018-11-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2018-11-30

Brief Summary

The prevalence of obesity and obesity-related complications is currently taking epidemic proportions. These complications increase the risk of type 2 diabetes and cardiovascular disease, which are important causes of morbidity and mortality worldwide.

It is important to gain insight in the mechanisms underlying obesity-related complications, because this may lead to the development of directed therapeutic strategies.

Currently, there is significant evidence that the cause of both insulin resistance and hypertension must be sought at the level of the microcirculation.

Over activity of the renin-angiotensin-aldosterone system is a potential cause of microvascular dysfunction. Angiotensin II was indeed found to be implicated in the pathogenesis of obesity-associated hypertension and insulin resistance, possibly through interference with the vascular effects of insulin.

Increased aldosterone levels have also been associated with resistant hypertension and insulin resistance, which is illustrated in patients with primary aldosteronism. Furthermore, aldosterone is known to exert several detrimental effects on the vasculature, some of which are offset by mineralocorticoid receptor antagonists.

In obese individuals, plasma aldosterone concentrations are increased as well. We hypothesize that increased aldosterone levels in adipose persons induce microvascular dysfunction, which contributes to the development of insulin resistance and hypertension, and mineralocorticoid receptor antagonism results in improved insulin sensitivity and decreased blood pressure by counteracting the adverse effects of aldosterone on the microvasculature.

Conditions

Abdominal Obesity Metabolic Syndrome; Insulin Resistance; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Eplerenone

Eplerenone 50 mg 1dd during four weeks

Group Type: ACTIVE_COMPARATOR

Eplerenone

Intervention Type: DRUG

Placebo

Eplerenone-matched placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Eplerenone-matched placebo

Interventions

Eplerenone

Intervention Type: DRUG

Placebo

Eplerenone-matched placebo

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 40-65 years
• Caucasian
• Waist circumference > 102 cm (men)/> 88 cm (women)
• Triglycerides > 1.7 mmol/L
• High-normal blood pressure (office blood pressure: 130/85 - 139/89 mm Hg) or stage I hypertension (office blood pressure: 140/90 mm Hg - 159/99 mm Hg; 24h ABPM: 125/80 - 149/89 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 glucose metabolism (fasting glucose values > 5.6 mmol/L)
• Grade 2 or 3 hypertension (office blood pressure: > 160/100 mm Hg; ABPM > 150/90 mm Hg)
• Unstable or severe pulmonary disease
• Unstable or severe thyroid disorders
• Inflammatory diseases
• Alcohol use > 2 U/day (women)/> 3 U/day (men)
• Use of antihypertensive, lipid-lowering or glucose-lowering medications,
• Use of corticosteroids, medication known to inhibit or induce CYP3A4, lithium, and tricyclic antidepressants or antipsychotic medication, and regular use (weekly or several times a week) of NSAIDs
• Plasma potassium levels < 3.2 mmol/L or > 5 mmol/L
• eGFR < 60 mL/min
• Impairment of hepatic function
• Pregnancy or lactation

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Monica Schütten

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

prof. C.D.A. Stehouwer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University

Maastricht, Limburg, Netherlands

Countries

Netherlands

Other Identifiers

133031

Identifier Type: -

Identifier Source: org_study_id