In this study we aim to elucidate effects of dietary sodium intake on:1. Body weight and blood pressure2. Microcirculation by studying the capillary network during high and low sodium conditions.3. Adaptive and innate immune system by studying…
ID
Source
Brief title
Condition
- Immune disorders NEC
- Vascular hypertensive disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be body weight and blood pressure, as represented by
the mean arterial pressure. Several secondary endpoints are proposed.
Secondary outcome
Concerning effects of sodium intake on microcirculation, the endpoint will be
capillary density and perfusion as assessed by Sidestream Darkfield (SDF)
imaging and retinal vascular imaging, in response to a high and a low sodium
diet. We will investigate whether changes in these parameters correlate with
changes in the macrocirculation. The influence of administration of
nitroglycerin, an endothelial-independent vasodilator, on microcirculatory
changes in the setting of either low or high salt intake will also be examined.
Concerning the effects of sodium intake on the immune system, we will assess
T-lymphocyte populations (i.e. IL-17, Th17), neutrophil subpopulations, and
monocyte subpopulations, by flow cytometry in different sodium conditions.
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. For a
substantial time, it was thought that sodium increases blood pressure via an
increase in extracellular volume. However, this assumption was challenged by
several sodium balance studies. Instead, recent animal studies point to a role
for the microcirculation and the immune system. These findings have not been
confirmed in human subjects. We want to investigate two patient groups that are
known to have alterations in their microcirculation as well as with alterations
in their immune system, possibly making them more susceptible to salt-sensitive
hypertension. In these patients, we want to assess whether they demonstrate a
sodium-induced body weight or blood pressure increase and if so, whether this
is related to microcirculatory or immunological changes. These two groups
comprise patients with type 1 diabetes mellitus (DM1) and psoriatic arthritis.
Study objective
In this study we aim to elucidate effects of dietary sodium intake on:
1. Body weight and blood pressure
2. Microcirculation by studying the capillary network during high and low
sodium conditions.
3. Adaptive and innate immune system by studying circulating T-lymphocyte
subpopulations,
neutrophil subpopulations, and monocyte subpopulations.
Study design
This study has a randomized experimental interventional cross-over study
design.
Intervention
dietary intervention: low sodium diet (<50 mmol Na+/d) vs high sodium diet
(>200 mmol Na+/d)
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 patients known to be prone
for (salt-sensitive) hypertension is 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 (<50 mmol Na+) and high sodium diet
(>200 mmol Na+) for two weeks each in random order. This intervention causes no
harm to the subject, as average sodium intake in males in the Netherlands
corresponds to 150-200 mmol daily. The patients 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.
Four (two times two) skin biopsies will be performed, which will be very small
in size and will cause only very minor to no scarring. All measurements will
cause minimal to no burden to the patient. During two study visits patients
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 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
All patients
- Male between 18 and 40 years of age
- Non-treated office blood pressure * 140/90 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, DM1 patients
- Known with Diabetes Mellitus type 1
- With or without microalbuminuria defined as:
o either albuminuria 20-200 mg/L in a morning urine sample
o or albuminuria 30-300 mg/24 hrs collected in a 24-hours urine
collection
o or albumin-to-creatinin ratio 2,5-25 mg/mmol in a morning urine
sample.
- Stable renal function (creatine clearance > 60 ml/min and < 6 ml/min
per year decline)
with or without on stable therapy with RAAS inhibiting agents
- HbA1c levels below 10.0% (86 mmol/mol) during the 6 months preceding the
study
- Multiple injections of insulin a day, Psoriatic arthritis patients
without IL-17 inhibitors
- Known with psoriatic arthritis, stable disease activity (mild or in
remission) as clinically
assessed by the treating rheumatologist
- Stable renal function (creatinin clearance > 60 ml/min and < 6 ml/min per
year decline, no
overt proteinuria)
- Without use of IL-17 inhibitors, IL-10 inhibitors, IL-23 inhibitors, and
leflunomide, Psoriatic arthritis patients with IL-17 inhibitors
- Known with psoriatic arthritis, stable disease activity (mild or in
remission) as clinically
assessed by the treating rheumatologist
- Stable renal function (creatinin clearance > 60 ml/min and < 6 ml/min per
year decline, no
overt proteinuria)
- Use of IL-17 inhibitors at least 3 months before screening
Exclusion criteria
Patients meeting any of the following exclusion criteria are not to be enrolled
in the study:
- An office blood pressure >140/90 mmHg
- A body mass index > 30 kg/m2
- Use of systemic corticosteroids
- Use of NSAIDS >2 times a week
- 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, excluding the diseases of interest (DM1 and
psoriatic arthritis)
- 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 other than DM1 and psoriatic arthritis
- 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 |
|---|---|
| Other | .... |
| CCMO | NL63332.018.18 |
| OMON | NL-OMON25435 |