Glucagon like Peptide -1 (GLP-1) receptor agonists are well known to stimulate glucose-induced insulin secretion and to reduce energy intake. Recent findings from animal and human studies suggest a role of GLP-1 in regulating water and salt homeostasis. GLP-1 has been shown to reduce fluid intake after an oral salt load or during a meal - pointing to a hypodipsic effect. The aim of this study is to elucidate whether these putative hypodipsic properties of GLP-1 might be of advantage in persons with an exaggerated thirst perception as is the case in patients with primary polydipsia.
GLP-1 analogues are currently used for the treatment of hyperglycaemia associated with type 2 diabetes mellitus and given his properties as a natural satiety hormone, the GLP-1 analogue liraglutide was recently approved by the FDA for weight management. In studies related to the influence of GLP-1 and -analogues in controlling food intake a concomitant reduction of fluid consumption has been observed. The investigators hypothesize that GLP-1 analogues not only modulate appetite and provide satiety but also reduce fluid intake and thirst sensation in humans - especially in those with excessive thirst perception (patients with primary polydipsia). In view of future therapeutic options for these patients we aim to investigate the influence of the long-acting GLP-1 analogue dulaglutide on fluid intake, thirst perception and quality of life in patients with primary polydipsia compared to placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
50
Treatment with dulaglutide for 3 weeks.
Treatment with Sodium Chloride 0.9% (Placebo) for 3 weeks.
University Hospital Basel
Basel, Switzerland
Fluid intake in ml
Fluid intake (ml) during an evaluation visit of 8 hours
Time frame: 8 hours
Quality of Life Assessment using the Short Form-12 (SF-12) Questionnaire
To assess the influence of dulaglutide on thirst perception and quality of life in patients with primary polydipsia compared to placebo.
Time frame: During phase a and b, 3 weeks each
24h-urine production
24h-urine production in ml during evaluation visit and thereafter
Time frame: 24 hours
Plasma- and urine osmolality
influence of dulaglutide on osmolality during evaluation visit
Time frame: change during evaluation visit of 8 hours
Circadian serum- and salivary cortisol levels
Influence of dulaglutide on hypothalamic-pituitary-adrenal axis (HPA axis) activity
Time frame: circadian rhythm assessed at timepoints 8am, 12am, 4pm, 8pm and 12pm
Cortisol levels basal and stimulated
Influence of dulaglutide on hypothalamic-pituitary-adrenal axis (HPA axis) activity
Time frame: Cortisol at timepoint 0 and after 20-30 minutes after synacthen injection
Copeptin level
Influence of dulaglutide on copeptin levels after a period of water deprivation
Time frame: at begin of evaluation 1 day visit after an overnight fast (no drink, no food)
Influence of dulaglutide on neuronal changes
Neuronal changes assessed with a functional magnet resonance Imaging between dulaglutide and Placebo Treatment in a subgroup of patients with primary polydipsia
Time frame: during phase a and b, 3rd week each for 15 patients
Neuronal changes between patients with primary polydipsia and healthy volunteers
Differences in neuronal changes assessed by functional magnet resonance imaging
Time frame: for patients during phase a and b, 3rd week each for 15 patients, 15 matched healthy control subjects
Thirst perception
Influence of dulaglutide on thirst perception
Time frame: during phase a and b, 3 weeks each and change during evaluation visit of 8 hours
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