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

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

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.

Study Overview

• Status: Completed
• Conditions: Water-Electrolyte Imbalance; Thirst
• Intervention / Treatment: Drug: Dulaglutide; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

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
Active Comparator: Dulaglutide; Dulaglutide (Trulicity®) 1.5 mg in 0.5 ml, via Pen s.c. once weekly for 3 weeks.	Drug: Dulaglutide; Evaluation visit with assessment of fluid intake; Other Names: Verum
Placebo Comparator: Placebo; 0.5 ml normal saline (0.9% sodium chloride), sc once weekly for 3 weeks.	Other: Placebo; Evaluation visit with assessment of fluid intake

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2016
• Primary Completion (Actual): May 1, 2017
• Study Completion (Actual): May 12, 2017

Study Registration Dates

• First Submitted: April 27, 2017
• First Submitted That Met QC Criteria: May 2, 2017
• First Posted (Actual): May 5, 2017

Study Record Updates

• Last Update Posted (Actual): October 25, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide
• Other Study ID Numbers: GATE

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No