Aldosterone, Microvascular Function and Salt-sensitivity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02068781
Recruitment Status : Completed
First Posted : February 21, 2014
Last Update Posted : May 19, 2017
Information provided by (Responsible Party):
Monica Schütten, Maastricht University Medical Center

Brief Summary:

Currently, the incidence of obesity and obesity-related disorders is reaching epidemic proportions, which entails an increasing burden for health care systems. The association of obesity with other risk factors for type 2 diabetes mellitus and cardiovascular disease, such as insulin resistance and hypertension, is often referred to as the metabolic syndrome. During recent years, salt-sensitivity of blood pressure has emerged as an additional cardiovascular risk factor that is related to obesity and other key components of the metabolic syndrome. The underlying pathophysiological mechanisms of these interrelationships are complex and incompletely elucidated. Microvascular dysfunction has been proposed as a link between insulin resistance and hypertension in obese individuals. In addition, impairment of microvascular function was found to be associated with salt-sensitivity of blood pressure. Increased aldosterone levels, as observed in obese individuals, might be a cause of microvascular dysfunction-induced salt-sensitivity and insulin resistance. Aldosterone not only gives rise to sodium-retention in the distal tubule of the kidney, but was also found to impair endothelial function and thus lower NO-availability, which is characteristic of microvascular dysfunction. In addition, elevated aldosterone levels are associated with both hypertension and insulin resistance, which is illustrated in patients with primary aldosteronism, but also in the general population.

The investigators hypothesize that increased aldosterone levels in obese individuals lead to impairment of microvascular function through reduction of NO-availability. This microvascular dysfunction is suggested to play a central role in the pathogenesis of salt-sensitive hypertension and insulin resistance.

Condition or disease Intervention/treatment Phase
Abdominal Obesity Metabolic Syndrome Sodium-sensitivity Insulin Resistance Hypertension Dietary Supplement: Low-sodium diet Dietary Supplement: High-sodium diet Not Applicable

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: Aldosterone-induced Microvascular Dysfunction as a Cause of Salt-sensitivity in Obesity?
Study Start Date : July 2014
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy Sodium
Drug Information available for: Aldosterone

Arm Intervention/treatment
Active Comparator: Start with low-sodium diet
One week of low-sodium diet, followed by a two-week wash-out period and subsequently, another week of high-sodium diet
Dietary Supplement: Low-sodium diet
50 mmol NaCl per 24h

Dietary Supplement: High-sodium diet
250 mmol NaCl per 24h

Active Comparator: Start with high-sodium diet
One week of high-sodium diet, followed by a two-week wash-out period and subsequently, another week of low-sodium diet
Dietary Supplement: Low-sodium diet
50 mmol NaCl per 24h

Dietary Supplement: High-sodium diet
250 mmol NaCl per 24h

Primary Outcome Measures :
  1. Difference in capillary recruitment between low- and high sodium diets [ Time Frame: One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized ]

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

Obese individuals

  • Age 18-65 years
  • Caucasian
  • Waist circumference > 102 cm (men)/> 88 cm (women)

Lean individuals

  • Age 18-65 years
  • Caucasian
  • Waist circumference < 94 cm (men)/< 80 cm (women)

Exclusion Criteria:

Obese/lean individuals

  • 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
  • Stage 3 hypertension (blood pressure > 180/110 mm Hg)
  • Unstable or severe pulmonary disease
  • Unstable or severe thyroid disorders
  • Inflammatory diseases
  • Smoking
  • Alcohol use > 2 U/day (women)/> 3 U/day (men)
  • Use of antihypertensive, lipid-lowering or glucose-lowering medications
  • Use of corticosteroids and regular use of NSAIDs
  • 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 identifier (NCT number): NCT02068781

Maastricht University
Maastricht, Limburg, Netherlands, 6229 ER
Sponsors and Collaborators
Maastricht University Medical Center
Principal Investigator: C.D.A. Stehouwer, MD, PhD Maastricht University Medical Center

Responsible Party: Monica Schütten, MD, Maastricht University Medical Center Identifier: NCT02068781     History of Changes
Other Study ID Numbers: 47438/IMP10124
First Posted: February 21, 2014    Key Record Dates
Last Update Posted: May 19, 2017
Last Verified: May 2017

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Obesity, Abdominal
Nutrition Disorders
Body Weight
Signs and Symptoms
Glucose Metabolism Disorders
Metabolic Diseases
Immune System Diseases