In this study we aim to elucidate effects of dietary sodium intake on:1. Microcirculation by studying the capillary network during high and low sodium conditions.2. Adaptive and innate immune system by studying circulating T-lymphocyte…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Several primary endpoints are proposed.
1. Microcirculation
A. To assess the effect of dietary sodium intake on capillary recruitment and
capillary perfusion determined by capillary density, proportion of perfused
density, microculatory flow index and tortuosity, assessed by SDF-imaging,
nailfold capillaroscopy and retinal vascular imaging.
B. To assess whether high sodium-induced changes in microcirculation can be
restored by nitroglycerin, being a NO donor to the capillary vessel bed.
2. Immune system
A. To assess whether different sodium intakes (high or low salt diet) will lead
to changes in circulating T-lymphocyte subpopulations (e.g., Th17 cells).
Secondary outcome
1. Microcirculation
C. To assess if microcirculatory changes in response to dietary sodium are
related to macrocirculatory changes, displayed by measurement of central and
peripheral blood pressure by use of continuous finger arterial pressure (FinAp)
waveform registration with the semi-automatic device Nexfin® and by using
radial pulse waveforms with the semi-automatic device Sphygmocor®.
3. Other
A. To assess whether different sodium intakes will lead to changes in eNOS and
RNA expression and sulfation of glycosaminoglycans (GAGs) of the skin. This
study is in line with other studies of our group studying the influence of
dietary salt intake (SALT and SALT-2 study). Due to used storage conditions
with formalin, techniques such as mass spectrometry, PCR or western blot are
not possible to perform on skin biopsies collected in the SALT studies.
Therefore we would like to use skin biopsies of this study in order to perform
these techniques. The skin biopsies derived from the SALT-studies will be used
to relate the effects of sodium intake on T-cell subpopulations, as part of the
current protocol, to influx of inflammatory cells into the skin (macrophages
and T-cells).
Background summary
Cardiovascular disease (CVD) is the leading cause of (premature) death in the
world. Arterial hypertension is one of the most important risk factors for
developing CVD. Currently in developed Western countries daily salt intake is 8
to 12 grams, well above the recommended daily intake. There is accumulating
evidence from human studies that high sodium intake is an important contributor
to development of hypertension and subsequent cardiovascular events. Structural
and functional changes of the microcirculation, consisting of all arterial
vessels that respond to increasing pressure by a myogenic reduction in lumen
diameter, as well as the capillaries and venules, are thought to play an
important role in the pathophysiology of hypertension. These microvessels have
an important role in the transportation of oxygen and nutrients to tissue
cells, and thus their adequate perfusion is essential for tissue and organ
function. A high salt diet can lead to changes in microvascular structure and
function independent of changes in blood pressure. Human studies on influence
of salt intake on microcirculation are mainly performed in hypertensive
subjects, so differentiation between the effect of salt intake or hypertension
by itself, or their combination remains difficult. Another, recently revealed,
contributor in the onset of hypertension is the immune system. Over the last
year there has been emerging evidence that both innate and adaptive immune
responses contribute to vascular dysfunction and hypertension. Recent
groundbreaking studies have linked the immune system to sodium homeostasis, and
consequently salt-sensitive hypertension. However these studies were only
carried out in animals or in vitro with human cells.
Study objective
In this study we aim to elucidate effects of dietary sodium intake on:
1. Microcirculation by studying the capillary network during high and low
sodium conditions.
2. Adaptive and innate immune system by studying circulating T-lymphocyte
subpopulations during high and low sodium conditions.
Study design
This study is a randomized experimental interventional cross-over study design
Intervention
All subjects will be asked to adhere to a low sodium diet (50 mmol Na/day)) and
a high sodium diet (200 mmol Na/day) for two weeks each in random order.
Furthermore, all subjects will receive one spray of nitroglycerin 0.4 mg
sublingual during the study visit 1 and 2.
Study burden and risks
Although this study is investigating two different systems of the human body,
it uses the same dietary intervention. When our hypotheses will be confirmed by
this study, further knowledge about the relation between microcirculation,
immune system, salt intake and hypertension in humans will be provided. Better
understanding of pathophysiological mechanisms in vivo are necessary in order
to provide support for new therapeutical strategies. Also, current
recommendations to reduce salt intake <5 grams daily will be supported.
Furthermore, it will strongly emphasize the use of this lifestyle modification
in primary prevention of hypertension. Morover, new therapeutic targets can be
revealed, and possibly point out a role for immunomodulating therapy in
treatment of hypertension.
Participating in this research project will not lead to personal benefit.
However, little to no burden is expected when participating in this study.
Participants are asked to adhere to a low and high sodium diet for two weeks
each in random order. The subjects will be asked to visit our research
department five times which will take approximately nine hours in total. The
study visits comprise venous blood drawings, collection of 24-hour urine
samples and 24-hour ambulant non-invasive measurements of central and
peripheral haemodynamics as well non-invasive assessment of microcirculation.
Two skin biopsies will be performed. All measurements will cause minimal to no
burden to the patient. During two study visits subjects will receive one spray
of sublingual nitroglycerin. This might cause transient headache and dizziness,
but because of the short half-life of nitroglycerin, this effect will last a
maximum of 30 minutes.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- 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 <= 130/85 mmHg
- A body mass index <= 30 kg/m2
- 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 >130/85 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 any auto-immune 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 eye-surgery, glaucoma or retinal eye disorder
- A history, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, THC, methamphetamine)
- A history of alcoholism and/or 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
- Smoking or use of tobacco products less then 30 days ago
- Any other issue that in opinion of the Investigator could be harmful to the subject or compromise interpretation of data
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL44788.018.13 |
| OMON | NL-OMON28966 |