Clinical trial NCT02770885: Effects of GLP-1 Analogues on Fluid Intake in Patients With Primary Polydipsia (The GOLD-Study)
Official title: Effects of GLP-1 Analogues on Fluid Intake in Patients With Primary Polydipsia: "The GOLD-Study"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Polydipsia
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2016-05-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fluid intake in ml
timeFrame: 8 hours
Secondary outcomes:
measure: Quality of Life Assessment using the Short Form-12 (SF-12) Questionnaire
timeFrame: During phase a and b, 3 weeks each
measure: 24h-urine production
timeFrame: 24 hours
measure: Plasma- and urine osmolality
timeFrame: change during evaluation visit of 8 hours
measure: Circadian serum- and salivary cortisol levels
timeFrame: circadian rhythm assessed at timepoints 8am, 12am, 4pm, 8pm and 12pm
measure: Cortisol levels basal and stimulated
timeFrame: Cortisol at timepoint 0 and after 20-30 minutes after synacthen injection
measure: Copeptin level
timeFrame: at begin of evaluation 1 day visit after an overnight fast (no drink, no food)
measure: Influence of dulaglutide on neuronal changes
timeFrame: during phase a and b, 3rd week each for 15 patients
measure: Neuronal changes between patients with primary polydipsia and healthy volunteers
timeFrame: for patients during phase a and b, 3rd week each for 15 patients, 15 matched healthy control subjects
measure: Thirst perception
timeFrame: during phase a and b, 3 weeks each and change during evaluation visit of 8 hours
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hospital of Basel
name: Mirjam Christ-Crain, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vukajlovic T, Sailer CO, Asmar A, Jensen BL, Vogt DR, Christ-Crain M, Winzeler B. Effect of a 3-Week Treatment with GLP-1 Receptor Agonists on Vasoactive Hormones in Euvolemic Participants. J Clin Endocrinol Metab. 2022 May 17;107(6):e2581-e2589. doi: 10.1210/clinem/dgac063.
citation: Winzeler B, Sailer CO, Coynel D, Zanchi D, Vogt DR, Urwyler SA, Refardt J, Christ-Crain M. A randomized controlled trial of the GLP-1 receptor agonist dulaglutide in primary polydipsia. J Clin Invest. 2021 Oct 15;131(20):e151800. doi: 10.1172/JCI151800.