The development of a thirst provocation test using the AVP receptor antagonist Tolvaptan for quantification of thirst sensation in various patient groups (obese patients with and without a history of bariatric surgery, patients with congestive heart failure and patients with cranial diabetes insipidus as compared to healthy controls) and genotyping of the AVP receptor 2.

In the clinic, several patient groups seem to have altered thirst sensation,
due to which they encounter problems in maintaining either a sufficient fluid
intake or, contrarily, an adequate fluid restriction. Obesity and bariatric
surgery (BS) are both associated with kidney stone formation. Therefore,
sufficient fluid intake is important in obese patients who underwent BS.
However, our impression from the clinic is that fluid intake in BS patients is
often insufficient. In contrast, patients with heart failure seem to have an
increased thirst sensation, which causes noncompliance to fluid restriction.
Finally, our impression from the clinic is that patients with cranial diabetes
insipidus experience increased thirst despite normal serum osmolality.

We aim to investigate thirst in the above mentioned patient groups, applying a
Visual Analogue Scale (VAS) and, where ethically acceptable, a new thirst
provocation test which we will develop in a group of healthy probands. Using
these tools, we aim to investigate whether thirst sensation is pathological, or
rather an adequate response to the clinical condition of these patients.

The thirst provocation test we aim to develop, involves the use of Tolvaptan (a
novel, arginine vasopressin receptor (AVPR) antagonist). Blocking the
antidiuretic effect of AVP by Tolvaptan causes hyperosmolarity and stimulation
of AVP secretion, which causes thirst in healthy individuals. First, healthy
probands meeting the inclusion criteria are invited to participate. The study
will last until the calculated number of patients is included. The thirst
provocation test will first be validated in 24 healthy probands. When the
thirst provocation test is validated, we will include the three patient groups
mentioned in the introduction, being obese patients, patients with heart
failure and patients with cranial diabetes insipidus. The number of patients
needed to obtain adequate statistical power will be calculated based on the
results found in healthy probands. Of all patients and healthy participants,
DNA will be isolated from blood and AVPR2 (encoding the AVP receptor 2) SNP
analysis will be performed using Taqman® assay. The relation between VAS scores
and AVPR2 genotype will be investigated using SPSS® 17.0 or Statgraphics® XVI.

None

Burden: 5,5 hours at the hospital, 5 venapunctions of 10 ml each.
Risks: possible adverse effects of Tolvaptan, hematoma of venapunction.
Benefit: our research might provide an explanation for our patients*
difficulties maintaining either a sufficient fluid intake or, contrarily, an
adequate fluid restriction. Furthermore, our results might lead to therapeutic
options in the future.