Role of endothelial surface layer in regulating the sodium balance and extracellular fluid volume

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 18

Inclusion Criteria

Healthy subjects
- Male between 18 and 40 years of age
- Healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination (PE) and laboratory tests carried out in the screening visit.
- Non-treated office blood pressure * 140/90 mmHg
- Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form

Exclusion Criteria

- An office blood pressure >140/90 mmHg
- A body mass index > 30 kg/m2
- A major illness in the past 3 months or any significant chronic medical illness that the Investigator would deem unfavourable for enrolment, including chronic inflammatory diseases
- A history of any type of malignancy within the past 5 years with the exception of successfully treated basal cell cancer of the skin
- A history of any renal disease
- A history of cardiovascular disease (in the past 6 months) defined as documented coronary artery disease including myocardial infarction, (un-)stable angina pectoris or acute coronary syndrome, precutenaous transluminal coronary angioplasty, coronary artery bypass grafting, cerebrovascular disease including ischemic and hemorrhagic stroke or a subarachnodial bleeding, or peripheral artery disease including aortic aneurysmata
- A history of coagulation disorders
- A history of primary hyperlipoproteinemias
- A history of hypersensitivity or allergy to iodium or to shell fish
- A history, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC, methamphetamine)
- A history of alcoholism and/or is drinking more than 3 units of alcohol per day. Alcoholism is defined as an average weekly intake of >21 units for males. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits
- Difficulty in donating blood or limited accessibility of a vein in left and right arm
- Subject has donated blood in last 3 months
- Use of tobacco products
- Any other issue that, in the opinion of the Investigator, could be harmful to the subject or compromise interpretation of the data
- Prior participation in a trial where the subject received intravenous endotoxin (LPS) infusion
- Any clinically relevant abnormality noted on the 12-lead ECG as judged by the Investigator or an average QTcB or QTcF > 450 millisec

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>We will study primarily the effects of a salt load on the haemodynamics and ECV<br /><br>in subjects with a presumed normal ESL in healthy subjects.<br /><br>Primary endpoint will be the ECV as represented by body weight and BP.<br /><br>Furthermore, the golden standard for ECV measurement will be performed. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Other study paramaters consist of indirect measurements of the ESL dynamics and<br /><br>function as assessed with intravital microscopy of the sublingual<br /><br>microvasculature and transcapillary escape rate (TER). We will study the<br /><br>kidney function as represented by the glomerular filtration rate (GFR),<br /><br>fractional Na+ excretion, albuminuria and proteinuria. Finally, skin biopsies<br /><br>will allow study of the role of interstitial GAGs and macrophage influx in<br /><br>response to a salt load.</p><br>

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