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Aldosterone Antagonism and Microvascular Function

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ClinicalTrials.gov Identifier: NCT01887119
Recruitment Status : Recruiting
First Posted : June 26, 2013
Last Update Posted : December 5, 2017
Information provided by (Responsible Party):
Monica Schütten, Maastricht University Medical Center

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.

Condition or disease Intervention/treatment Phase
Abdominal Obesity Metabolic Syndrome Insulin Resistance Hypertension Drug: Eplerenone Other: Placebo Phase 4

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Aldosterone Antagonism on Insulin-mediated Microvascular Function in Subjects With the Metabolic Syndrome
Study Start Date : October 2013
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Active Comparator: Eplerenone
Eplerenone 50 mg 1dd during four weeks
Drug: Eplerenone
Placebo Comparator: Placebo
Eplerenone-matched placebo
Other: Placebo
Eplerenone-matched placebo

Primary Outcome Measures :
  1. 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 ]
    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)

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Ages Eligible for Study:   40 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01887119

Contact: Monica Schütten m.schutten@maastrichtuniversity.nl

Maastricht University Recruiting
Maastricht, Limburg, Netherlands, 6229 ER
Contact: Monica Schütten       m.schutten@maastrichtuniversity.nl   
Sponsors and Collaborators
Maastricht University Medical Center
Principal Investigator: prof. C.D.A. Stehouwer, MD, PhD Maastricht University Medical Center

Responsible Party: Monica Schütten, MD, Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01887119     History of Changes
Other Study ID Numbers: 133031
First Posted: June 26, 2013    Key Record Dates
Last Update Posted: December 5, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Obesity, Abdominal
Pathologic Processes
Nutrition Disorders
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents