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

Primary Polydipsia Clinical Trial

— GOLD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02770885
• Other study ID #: GOLD 2016
• Status: Completed
• Phase: Phase 2
• Start date: March 2016
• Est. completion date: October 7, 2019

Study information

• Verified date: January 2020
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 7, 2019
• Est. primary completion date: May 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Insipidus
• Polydipsia
• Primary Polydipsia

Intervention

Drug:
• Dulaglutide
Treatment with dulaglutide for 3 weeks.
• Placebo
Treatment with Sodium Chloride 0.9% (Placebo) for 3 weeks.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fluid intake in ml	Fluid intake (ml) during an evaluation visit of 8 hours	8 hours
Secondary	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
Secondary	24h-urine production	24h-urine production in ml during evaluation visit and thereafter	24 hours
Secondary	Plasma- and urine osmolality	influence of dulaglutide on osmolality during evaluation visit	change during evaluation visit of 8 hours
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	Thirst perception	Influence of dulaglutide on thirst perception	during phase a and b, 3 weeks each and change during evaluation visit of 8 hours