Primary Polydipsia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGDulaglutide
Treatment with dulaglutide for 3 weeks.
DRUGPlacebo
Treatment with Sodium Chloride 0.9% (Placebo) for 3 weeks.
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age over 18 years * Polyuria of \> 50 ml/Kg/day * Polydipsia of \> 3 liters/day
Exclusion criteria
* Known or probable central or nephrogenic Diabetes insipidus, expected from patient's history * Polyuria secondary to diabetes mellitus, hypokalemia, hypercalcemia * Pregnancy * Previous treatment with GLP-1 agonists within the last 3 month * History of pancreatitis * Severe renal insufficiency (eGFR (CKD EPI) \<30 ml/min/1,73 m2) * Cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fluid intake in ml | 8 hours | Fluid intake (ml) during an evaluation visit of 8 hours |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24h-urine production | 24 hours | 24h-urine production in ml during evaluation visit and thereafter |
| Plasma- and urine osmolality | change during evaluation visit of 8 hours | influence of dulaglutide on osmolality during evaluation visit |
| Circadian serum- and salivary cortisol levels | circadian rhythm assessed at timepoints 8am, 12am, 4pm, 8pm and 12pm | Influence of dulaglutide on hypothalamic-pituitary-adrenal axis (HPA axis) activity |
| Cortisol levels basal and stimulated | Cortisol at timepoint 0 and after 20-30 minutes after synacthen injection | Influence of dulaglutide on hypothalamic-pituitary-adrenal axis (HPA axis) activity |
| Quality of Life Assessment using the Short Form-12 (SF-12) Questionnaire | During phase a and b, 3 weeks each | To assess the influence of dulaglutide on thirst perception and quality of life in patients with primary polydipsia compared to placebo. |
| Influence of dulaglutide on neuronal changes | during phase a and b, 3rd week each for 15 patients | Neuronal changes assessed with a functional magnet resonance Imaging between dulaglutide and Placebo Treatment in a subgroup of patients with primary polydipsia |
| Neuronal changes between patients with primary polydipsia and healthy volunteers | for patients during phase a and b, 3rd week each for 15 patients, 15 matched healthy control subjects | Differences in neuronal changes assessed by functional magnet resonance imaging |
| Thirst perception | during phase a and b, 3 weeks each and change during evaluation visit of 8 hours | Influence of dulaglutide on thirst perception |
| Copeptin level | at begin of evaluation 1 day visit after an overnight fast (no drink, no food) | Influence of dulaglutide on copeptin levels after a period of water deprivation |
Countries
Switzerland
Outcome results
None listed