Aldosterone, Microvascular Function and Salt-sensitivity

NCT ID: NCT02068781

Last Updated: 2017-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2016-10-31

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.

Conditions

Abdominal Obesity; Metabolic Syndrome; Sodium-sensitivity; Insulin Resistance; Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Low-sodium diet

Intervention Type: DIETARY_SUPPLEMENT

50 mmol NaCl per 24h

High-sodium diet

Intervention Type: DIETARY_SUPPLEMENT

250 mmol NaCl per 24h

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

Group Type: ACTIVE_COMPARATOR

Low-sodium diet

Intervention Type: DIETARY_SUPPLEMENT

50 mmol NaCl per 24h

High-sodium diet

Intervention Type: DIETARY_SUPPLEMENT

250 mmol NaCl per 24h

Interventions

Low-sodium diet

50 mmol NaCl per 24h

Intervention Type: DIETARY_SUPPLEMENT

High-sodium diet

250 mmol NaCl per 24h

Intervention Type: DIETARY_SUPPLEMENT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Monica Schütten

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

C.D.A. Stehouwer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Center

Locations

Maastricht University

Maastricht, Limburg, Netherlands

Countries

Netherlands

References

Zhou TL, Schutten MTJ, Kroon AA, Henry RMA, Houben AJHM, van der Kallen CJH, van Greevenbroek MMJ, de Leeuw PW, Stehouwer CDA. Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population. J Am Heart Assoc. 2023 Jan 3;12(1):e026578. doi: 10.1161/JAHA.122.026578. Epub 2022 Dec 24.

Reference Type: DERIVED

PMID: 36565181 (View on PubMed)

Schutten MT, Kusters YH, Houben AJ, Niessen HE, Op 't Roodt J, Scheijen JL, van de Waardenburg MP, Schalkwijk CG, de Leeuw PW, Stehouwer CD. Glucocorticoids affect metabolic but not muscle microvascular insulin sensitivity following high versus low salt intake. JCI Insight. 2020 Mar 26;5(6):e127530. doi: 10.1172/jci.insight.127530.

Reference Type: DERIVED

PMID: 32107343 (View on PubMed)

Other Identifiers

47438/IMP10124

Identifier Type: -

Identifier Source: org_study_id