Effects of Glucagon Like Peptide 1 (GLP-1) Analogues on Fluid Intake

Study Overview
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Brief Summary
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The aim of this study is to elucidate whether GLP-1 analogues influence not only appetite but also thirst perception. It is hypothesized that GLP-1 analogues reduce fluid intake in healthy volunteers compared to Placebo.

Detailed Description
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GLP-1 analogues 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 analogues reduce fluid intake in healthy volunteers compared to placebo assessed during an evaluation visit of 8 hours.

Official Title
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Effects of GLP-1 Analogues on Fluid Intake in Healthy Volunteers - The GATE-Study

Conditions
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Thirst, Water-Electrolyte Imbalance

Intervention / Treatment
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* Drug: Dulaglutide
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Age 18 to 65 years Exclusion Criteria: Known or probable central or nephrogenic Diabetes insipidus, based on patient's history Polyuria secondary to diabetes mellitus, hypokalemia, hypercalcemia Primary Polydipsia, defined as more than 4 liters fluid intake per day BMI <18 or >30kg/m2 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
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: Double-blind, placebo control, cross-over design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dulaglutide<br>Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via Pen s.c. once weekly for 3 weeks. | Drug: Dulaglutide<br>* Evaluation visit with assessment of fluid intake<br>* Other names: Verum;|
| Placebo Comparator: Placebo<br>0.5 ml normal saline (0.9% sodium chloride), sc once weekly for 3 weeks. | Other: Placebo<br>* Evaluation visit with assessment of fluid intake<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thirst | Thirst perception | 8 hours | 
| Urine volume | Urine volume in ml | 24 hours | 
| Urinary sodium | Urinary sodium excretion | 24 hours | 
| Electrolytes | Plasma electrolytes | 3 timpoints during 8 hours | 
| Urine electrolytes | Urine electrolytes | 3 timpoints during 8 hours | 
| copeptin | copeptin values | 3 timpoints during 8 hours | 
| renin | renin | 3 timpoints during 8 hours | 
| aldosterone | aldosterone | 3 timpoints during 8 hours | 
| Water and Salt | Brain Natriuretic Peptide (BNP) | 3 timpoints during 8 hours | 
| GLP-1 | GLP-1 | 3 timpoints during 8 hours | 
| Hypothalamus Pituitary Adrenal Axis (HPA) | cortisol value after Dexamethasone intake | 8 hours after Dexamethasone intake | 
| circadian rhythm | circadian rhythm of serum cortisol | 16 hours | 
| salivary cortisol | circadian rhythm of salivary cortisol | 16 hours | 
| ACTH | circadian rhythm of ACTH | 16 hours | 
| Hypothalamus Pituitary Adrenal Axis (HPA) | cortisol upon adrenocorticotropic hormone (ACTH) stimulation | 0.5 hours | 
| Hypothalamus Pituitary Adrenal Axis (HPA) | free urinary cortisol | 24 hours |