Effects of GLP-1 Analogues on Fluid Intake in Patients With Primary Polydipsia (The GOLD-Study)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of GLP-1 Analogues on Fluid Intake in Patients With Primary Polydipsia: The GOLD-Study

Conditions
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Primary Polydipsia

Intervention / Treatment
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* Drug: Dulaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Verum first<br>Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via Pen s.c. once weekly for 3 weeks. | Drug: Dulaglutide<br>* Treatment with dulaglutide for 3 weeks.<br>* Other names: Trulicity;|
| Placebo Comparator: Placebo first<br>Placebo: 0.5 ml normal saline (0.9% sodium chloride [0.9% sodium chloride (NaCl)]), injection sc via syringe once weekly for 3 weeks. | Drug: Placebo<br>* Treatment with Sodium Chloride 0.9% (Placebo) for 3 weeks.<br>* Other names: Sodium Chloride 0.9%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid intake in ml | Fluid intake (ml) during an evaluation visit of 8 hours | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | During phase a and b, 3 weeks each | 
| 24h-urine production | 24h-urine production in ml during evaluation visit and thereafter | 24 hours | 
| Plasma- and urine osmolality | influence of dulaglutide on osmolality during evaluation visit | change during evaluation visit of 8 hours | 
| Circadian serum- and salivary cortisol levels | Influence of dulaglutide on hypothalamic-pituitary-adrenal axis (HPA axis) activity | 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 | 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 | 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 | 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 | 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 | during phase a and b, 3 weeks each and change during evaluation visit of 8 hours |