NCT02068781

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jul 2014

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 19, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 21, 2014

Completed
4 months until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2016

Completed
Last Updated

May 19, 2017

Status Verified

May 1, 2017

Enrollment Period

2.3 years

First QC Date

February 19, 2014

Last Update Submit

May 18, 2017

Conditions

Abdominal ObesityMetabolic SyndromeSodium-sensitivityInsulin ResistanceHypertension

Outcome Measures

Primary Outcomes (1)

  • Difference in capillary recruitment between low- and high sodium diets

    One week low-sodium diet; wash-out period of two weeks; one week high-sodium diet; order of respective diets is randomized

Study Arms (2)

Start with low-sodium diet

ACTIVE COMPARATOR

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 dietDietary Supplement: High-sodium diet

Start with high-sodium diet

ACTIVE COMPARATOR

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 dietDietary Supplement: High-sodium diet

Interventions

Low-sodium dietDIETARY_SUPPLEMENT

50 mmol NaCl per 24h

Start with high-sodium dietStart with low-sodium diet
High-sodium dietDIETARY_SUPPLEMENT

250 mmol NaCl per 24h

Start with high-sodium dietStart with low-sodium diet

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Maastricht University

Maastricht, Limburg, 6229 ER, Netherlands

Location

Related Publications (2)

  • 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.

    PMID: 36565181DERIVED

  • 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.

    PMID: 32107343DERIVED

MeSH Terms

Conditions

Obesity, AbdominalMetabolic SyndromeInsulin ResistanceHypertension

Interventions

Diet, Sodium-Restricted

Condition Hierarchy (Ancestors)

ObesityOverweightOvernutritionNutrition DisordersNutritional and Metabolic DiseasesBody WeightSigns and SymptomsPathological Conditions, Signs and SymptomsHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Diet TherapyNutrition TherapyTherapeuticsDietNutritional Physiological PhenomenaDiet, Food, and NutritionPhysiological Phenomena

Study Officials

  • C.D.A. Stehouwer, MD, PhD

    Maastricht University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

February 19, 2014

First Posted

February 21, 2014

Study Start

July 1, 2014

Primary Completion

October 1, 2016

Study Completion

October 1, 2016

Last Updated

May 19, 2017

Record last verified: 2017-05

Locations

NL(1)