To assess the timed effects of a matched acute oral sodium load (in the absence or presence of GLP-1 receptor agonist) or an acute intravenous sodium load in T2DM patients with/without renal impairment on urinary sodium excretion after 24h,…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Nephropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Urinary sodium excretion 24h after a matched acute oral sodium load (in the
absence or presence of GLP-1 receptor agonist) or an acute intravenous sodium
load in T2DM patients with/without renal impairment, determined by the
cumulative sodium balance.
Secondary outcome
Variation in blood pressure, determined by non-invasive, automated,
beat-to-beat blood pressure monitor (Nexfin®) measurements and 24h ABPM device,
differences in total and fractional urinary sodium excretion and total sodium
balance after 2, 4 and 6 hours, differences in plasma, urine and systemic
hemodynamic markers, which include plasma hematocrit, hemoglobin, MCV, sodium,
potassium, creatinine, urea, bicarbonate, chloride, glucose and GFR, urine
creatinine, albumin, urea, osmolality, glucose, Na+, K+, Cl- (fractional and
24h collection), systemic hemodynamic; Cardiac output, peripheral vascular
resistance, central blood pressure, heart rate and pulse wave velocity by
application tonometry
Background summary
In healthy individuals, the incretin effect (i.e. insulinotropic effects of the
gut-hormone glucagon-like peptide (GLP)-1) plays an important role in the
regulation of postprandial glucose metabolism. Several studies have shown that
the incretin effect is reduced in diabetes mellitus type 2 (T2DM) patients and
can be restored by raising GLP-1 concentrations to pharmacological levels. It
has been proposed that GLP-1, in addition to acting as a glucose/nutrient
sensor, may also be a major regulator of water and electrolyte balance in the
postprandial state through rapid feed-forward effects on the kidney. In line
with these observations, our research group has published several papers in
which short-term and long-term treatment with GLP-1 receptor agonists was shown
to induce renal sodium excretion in the fasted state. This could be of
importance given the association of increased sodium intake and both
cardiovascular and renal disease. Although the incretin effect in relation to
glucose has been studied thoroughly, the role of sodium in GLP-1 production
remains unclear. To our knowledge there are no sodium load studies in patients
with chronic kidney disease or/and T2DM, in which the relation between GLP-1
and the renal effects were studied.
Study objective
To assess the timed effects of a matched acute oral sodium load (in the absence
or presence of GLP-1 receptor agonist) or an acute intravenous sodium load in
T2DM patients with/without renal impairment on urinary sodium excretion after
24h, determined by the cumulative sodium balance.
Study design
This is an randomized open label cross-over study design
Study burden and risks
Possible benefits for participants: There are no benefits expected for the
participants.
Possible inconvenience for participants:
With regard to the used testagents, the Infusion of Iohexol can lead to a warm,
sometimes painful sensation. Most common but rare adverse effects are headache,
stiffness, nerve pain, nausea, vomiting, fever, hives, stomach pain,
hallucinations and neurological changes. In patients with an allergy for iodide
it can elicit hypersensitive reactions, therefore we specifically check a for
this allergy at screening.
Based on the positive feedback from our participants, the low drop-out rate
(max 5%) and the large proportion of participants that returns to participate
in yet another (similarly demanding) study, we are confident that the burden on
participants is perceived as not being too high. Indeed, we have built in
different ways to alleviate the burden for participants, including clear,
repeated communication, frequent contacting, intensified (diabetes) care,
24-hour availability of research staff, study and travel reimbursement.
Iohexol administration will not cause an increased discomfort, however patients
who have an allergy for iodine are not allowed to participate due to the risk
on an allergic reaction.
We are aware of the fact that in the current study participants will undergo
multiple tests that demand a considerable time investment from their end. For
all the participants the total duration
of the visits is estimated at 24 hours.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Group 2: T2DM patients without impaired kidney function
* Male between 40 and 75 years old
* Caucasian
* Average daily sodium intake of 150 mmol/day
* Known with Diabetes Mellitus - type 2, according to the ADA criteria
* Without macroalbuminuria defined as albumin-to-creatinine ratio >300 mg/mmol
in a morning urine sample.
* Stable renal function (creatinine clearance > 60 ml/min and < 6 ml/min per
year decline) with or without stable therapy with RAAS inhibiting agents
* HbA1c levels between 6.0 and 10.0% (42-86 mmol/mol) during the 6 months
preceding the study
* Hypertension should be controlled, i.e. * 140/90 mmHg.
* Able to provide written informed consent
Exclusion criteria
* An office blood pressure >160/90 mmHg
* 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
* Current use of the following medication: thiazolidinediones, GLP-1 receptor
agonists, DPP-4 inhibitors, oral glucocorticoids, immune suppressants,
antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic
antidepressants, diuretics and monoamine oxidase inhibitors, short-acting
insulin, < 3 months on stable dose of long-acting insulin, SGLT-2 inhibitors
* 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 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, 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
- Iodine allergy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL70824.029.19 |