Aldosterone, Microvascular Function and Salt-sensitivity

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Maastricht University Medical Center
Sponsor:
Information provided by (Responsible Party):
Monica Schütten, Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT02068781
First received: February 19, 2014
Last updated: July 31, 2014
Last verified: February 2014
  Purpose

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 Intervention Phase
Abdominal Obesity
Metabolic Syndrome
Sodium-sensitivity
Insulin Resistance
Hypertension
Dietary Supplement: Low-sodium diet
Dietary Supplement: High-sodium diet
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Aldosterone-induced Microvascular Dysfunction as a Cause of Salt-sensitivity in Obesity?

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: July 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT02068781

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

Locations
Netherlands
Maastricht University Recruiting
Maastricht, Limburg, Netherlands, 6229 ER
Sponsors and Collaborators
Maastricht University Medical Center
Investigators
Principal Investigator: 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: NCT02068781     History of Changes
Other Study ID Numbers: 47438
Study First Received: February 19, 2014
Last Updated: July 31, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Additional relevant MeSH terms:
Insulin Resistance
Metabolic Syndrome X
Glucose Metabolism Disorders
Metabolic Diseases
Hypertension
Obesity
Obesity, Abdominal
Vascular Diseases
Cardiovascular Diseases
Hyperinsulinism
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms

ClinicalTrials.gov processed this record on August 18, 2014