Primary objective is: - To evaluate the effects of (controlled) dehydration on coagulation and fibrinolytic parameters.Secondary objectives are:- To evaluate whether the response of coagulation and fibrinolytic parameters to dehydration is mediated…
ID
Source
Brief title
Condition
- Other condition
- Endocrine and glandular disorders NEC
Synonym
Health condition
vochthuishouding
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Coagulation and fibrinolysis activation markers: F1+2 (fragment 1+2), ETP
(endogenous thrombin potential), D-dimer, Plasminogen Activator Inhibitor-1
(PAI-1) activity.
Endothelial cell activation and platelet activation markers: von Willebrand
factor activity (vWf:C), clotting factor VIII activity (fVIII:C).
Blood coagulation time: PT.
Secondary outcome
urine osmolality, plasma osmolality, antidiuretic hormone, hematocrit.
Background summary
The therapeutic use of ADH is still under investigation. Desmopressin, a
synthetic analogue of the natural pituitary hormone ADH (DDAVP), has been
widely used in several European countries as an alternative to the use of blood
products in the treatment of von Willebrand disease and mild hemophilia A. It
was discovered that this drug, when administered either intranasally or
intravenously, results in a rapid two- to threefold increase in all components
of the factor VIII system. Due to this fast action, it was always believed that
DDAVP does not stimulate the production of coagulation factors, but rather a
release of pre-made factors from storage granules in the endothelial cells.
Although the effects of administered DDAVP in von Willebrand disease, mild
hemophilia A and even healthy subjects on haemostasis have been the subject of
extensive investigation, the physiologic effects of fluid deprivation and
subsequent, physiologic, rise of ADH on coagulation and fibrinolysis has not
yet been investigated.
Study objective
Primary objective is:
- To evaluate the effects of (controlled) dehydration on coagulation and
fibrinolytic parameters.
Secondary objectives are:
- To evaluate whether the response of coagulation and fibrinolytic parameters
to dehydration is mediated by ADH.
Study design
Clinical controlled trial/pilot study
Study burden and risks
healthy volunteers: No fluidintake for a long period of time can lead to
symptoms of dehydration such as dry mouth and headache. These symptoms are
harmless, especially given the short duration of the test, and will disappear
after drinking normally when the test is stopped. If the weight decreases by
more than 5%, the test will be stopped immediately. The bloodpressure will be
closely monitored, both in standing and supine position. Throughout the trial,
a research physician and a nurse are present during the water deprivation test.
DI patients: patients with diabetes insipidus, when not drinking sufficiently,
have a greater chance of getting symptoms of dehydration such as dry mouth and
headache. We ask these patients to continuesly drink enough fluids, as much as
the body indicates. Nevertheless, when the DI patient experiences severe
symptoms of dehydration such as weight loss of more than 2.5-3.0 kg or when
they no longer producing urine, they will be instructed to immediately use the
synthetic ADH and contact the study doctor or the emergency room at the
Slotervaart hospital.
Louwesweg 6
1066 EC Amsterdam
NL
Louwesweg 6
1066 EC Amsterdam
NL
Listed location countries
Age
Inclusion criteria
a. Adults >= 18 years old.
b. Able to provide informed consent.
c. Diagnosis of central diabetes insipidus (DI). (only for patients)
Exclusion criteria
a. Strong suspection of an infection of any cause
b. Primary polydipsia and diabetes insipidus (for the healthy volunteers).
c. Untreated thyroid and adrenal hormone abnormalities.
d. Pregnancy or puerperium.
e. Common etiologies of the syndrome of inappropriate antidiuretic hormone (SIADH); Active malignancy, inflammatory diseases (multiple sclerosis, meningitis, systemic lupus erythematosus), acquired immuno- deficiency syndrome (AIDS), infections (tuberculosis, pneumonia, empyema) (only for those 6 patients without signs of infection), cystic fibrosis, drugs (Selective serotonine reuptake inhibitors, tricyclic antidepressants, carbamazepine, clofibrate, narcotics, antipsychotic drugs, cytotoxic drugs)
f. Potentiation of AVP antidiuretic effects: desmopressin, vasopressin, oxytocin, prostaglandin synthesis inhibitors
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 | NL36972.048.11 |