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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Polydipsia
• Intervention / Treatment: Drug: Dulaglutide; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum first; Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via Pen s.c. once weekly for 3 weeks.	Drug: Dulaglutide; Treatment with dulaglutide for 3 weeks.; Other Names: Trulicity
Placebo Comparator: Placebo first; 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; Treatment with Sodium Chloride 0.9% (Placebo) for 3 weeks.; Other Names: Sodium Chloride 0.9%

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof, University Hospital of Basel

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): May 17, 2019
• Study Completion (Actual): October 7, 2019

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (Estimate): May 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 16, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Kidney Diseases; Urologic Diseases; Neurobehavioral Manifestations; Endocrine System Diseases; Pituitary Diseases; Diabetes Insipidus; Polydipsia; Polydipsia, Psychogenic; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: GOLD 2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No