Aldosterone Antagonism and Microvascular Function

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Maastricht University Medical Center
Sponsor:
Information provided by (Responsible Party):
Monica Schütten, Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01887119
First received: June 19, 2013
Last updated: January 14, 2014
Last verified: January 2014

June 19, 2013
January 14, 2014
October 2013
March 2015   (final data collection date for primary outcome measure)
Change in capillary recruitment (insulin-induced increase in microvascular blood volume in skeletal muscle) from baseline after 4 weeks of Eplerenone treatment or placebo [ Time Frame: Change from baseline after 4 weeks of treatment with either Eplerenone or placebo ] [ Designated as safety issue: No ]
The difference in microvascular blood volume in skeletal muscle of the forearm, which is assessed with contrast enhanced ultrasound, before and during a hyperinsulinemic, euglycemic clamp (performed to determine insulin sensitivity)
Same as current
Complete list of historical versions of study NCT01887119 on ClinicalTrials.gov Archive Site
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Aldosterone Antagonism and Microvascular Function
Effects of Aldosterone Antagonism on Insulin-mediated Microvascular Function in Subjects With the Metabolic Syndrome

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.

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Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
  • Abdominal Obesity Metabolic Syndrome
  • Insulin Resistance
  • Hypertension
  • Drug: Eplerenone
  • Other: Placebo
    Eplerenone-matched placebo
  • Active Comparator: Eplerenone
    Eplerenone 50 mg 1dd during four weeks
    Intervention: Drug: Eplerenone
  • Placebo Comparator: Placebo
    Eplerenone-matched placebo
    Intervention: Other: Placebo
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
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March 2015   (final data collection date for primary outcome measure)

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
Both
40 Years to 65 Years
Yes
Contact: Monica Schütten m.schutten@maastrichtuniversity.nl
Netherlands
 
NCT01887119
133031
No
Monica Schütten, Maastricht University Medical Center
Maastricht University Medical Center
Not Provided
Principal Investigator: prof. C.D.A. Stehouwer, MD, PhD Maastricht University Medical Center
Maastricht University Medical Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP