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
  Purpose

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 Intervention Phase
Abdominal Obesity Metabolic Syndrome
Insulin Resistance
Hypertension
Drug: Eplerenone
Other: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Effects of Aldosterone Antagonism on Insulin-mediated Microvascular Function in Subjects With the Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • 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)


Estimated Enrollment: 60
Study Start Date: October 2013
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Eplerenone
Eplerenone 50 mg 1dd during four weeks
Drug: Eplerenone
Placebo Comparator: Placebo
Eplerenone-matched placebo
Other: Placebo
Eplerenone-matched placebo

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01887119

Contacts
Contact: Monica Schütten m.schutten@maastrichtuniversity.nl

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

No publications provided

Responsible Party: Monica Schütten, MD, Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01887119     History of Changes
Other Study ID Numbers: 133031
Study First Received: June 19, 2013
Last Updated: January 14, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Hypertension
Insulin Resistance
Obesity
Obesity, Abdominal
Metabolic Syndrome X
Vascular Diseases
Cardiovascular Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Eplerenone
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014