Effects of GLP-1 Analogues on Fluid Intake in Patients With Primary Polydipsia (The GOLD-Study)
- Registration Number
- NCT02770885
- Lead Sponsor
- University Hospital, Basel, Switzerland
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- Age over 18 years
- Polyuria of > 50 ml/Kg/day
- Polydipsia of > 3 liters/day
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Verum first Dulaglutide Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via Pen s.c. once weekly for 3 weeks. Placebo first Placebo Placebo: 0.5 ml normal saline (0.9% sodium chloride \[0.9% sodium chloride (NaCl)\]), injection sc via syringe once weekly for 3 weeks.
- Primary Outcome Measures
Name Time Method Fluid intake in ml 8 hours Fluid intake (ml) during an evaluation visit of 8 hours
- Secondary Outcome Measures
Name Time Method 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.
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
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
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
Trial Locations
- Locations (1)
University Hospital Basel
🇨🇭Basel, Switzerland