Copeptin After a Subcutaneous Stimulation With Glucagon in Adults (Glucacop)

Copeptin After a Subcutaneous Stimulation With Glucagon in Adults (Healthy Volunteers and Patients With Diabetes Insipidus or Primary Polydipsia) - The Glucacop-Study

This study is to evaluate copeptin values after the subcutaneous injection of glucagon in adults (healthy volunteers and patients with diabetes insipidus or primary polydipsia). It is to investigate whether glucagon stimulates the release of copeptin as a surrogate of vasopressin.

Study Overview

• Status: Completed
• Conditions: Diabetes Insipidus
• Intervention / Treatment: Diagnostic test: Glucagon; Diagnostic test: Placebo

Detailed Description

The differentiation between central diabetes insipidus (cDI) and primary polydipsia (PP) is cumbersome. To date the test with the highest diagnostic accuracy is copeptin measurement after hypertonic saline Infusion.

Instead of hypertonic saline Infusion, arginine infusion - known to stimulate growth hormone - is a potent stimulator of the neurohypophysis and provides a new diagnostic tool in the differential diagnosis of cDI. Copeptin measurements upon arginine stimulation discriminated patients with diabetes insipidus vs. patients with primary polydipsia with a high diagnostic accuracy of 94%. Glucagon has been shown to stimulate GH-secretion. In analogy to the known stimulatory effect of arginine Infusion it is hypothesized that glucagon might stimulate the posterior pituitary gland and could therefore be a novel diagnostic test in the polyuria-polydipsia syndrome.

This study is to evaluate copeptin values after the subcutaneous injection of glucagon in adults (healthy volunteers and patients with diabetes insipidus or primary polydipsia).

This study is planned as a double-blind randomized-controlled cross-over trial consisting of two parts, including healthy adults (study part 1 - proof of concept) and adults with known diagnosis of cDI or PP (study part 2 - pilot study). Study parts 1 and 2 will be conducted consecutively. If the results of study part 1 suggest that glucagon is a potent stimulator of Copeptin in healthy adults, study part 2 will be conducted. Participants will receive glucagon injection and placebo injection in random order.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Divison of Endocrinology, Diabetes and Metabolism,University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria for healthy volunteers:

• no medication except hormonal contraception

Inclusion criteria for patients:

• Documented primary polydipsia or diabetes insipidus based on a water deprivation test or hypertonic saline Infusion
• Accordingly patients must have evidence of disordered drinking habits and diuresis defined as polyuria >50ml/kg body weight/24h and polydipsia >3l /24h, or must be on regular daily Desmopressin medication.

Exclusion Criteria for healthy volunteers:

• BMI > 25kg/m2 or < 18.5 kg/m2
• participation in a trial with investigational drugs within 30 days
• vigorous physical exercise within 24 hours before the study participation
• Alcohol intake within 24 hours before study participation
• pregnancy and breastfeeding
• Evidence of disordered drinking habits and diuresis defined as polyuria >50ml/kg Body weight/24h and polydipsia >3l /24h
• Intention to become pregnant during the study
• Known allergy towards glucagon
• Evidence of an acute illness
• Long QT syndrome
• Hemoglobin level below 120 g/l

Exclusion criteria for patients:

• BMI > 25kg/m2 or < 18.5 kg/m2
• participation in a trial with investigational drugs within 30 days
• vigorous physical exercise within 24 hours before the study participation
• Alcohol intake within 24 hours before study participation
• pregnancy and breastfeeding
• Evidence of an acute illness
• Long QT syndrome
• Hemoglobin level below 120 g/l

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: study part 1: healthy adult volunteers; 22 Healthy volunteers: The half of the study group will start with test day A (injection of glucagon), followed by test day B (injection of placebo) and the other half will start with test day B (injection of placebo), followed by test day A (injection of glucagon).	Diagnostic test: Glucagon; Glucagon with the empirical formula of C153H225N43O49S, and a molecular weight of 3483 g/mol, is a single-chain polypeptide containing 29 amino acid residues. Glucagon is provided in a single dose vial as powder. One container contains 1 mg of glucagon which results in a concentration of 1 mg/ml after dissolution in a volume of 1 ml (Glucagen NovoNordisk (Hypokit)). The currently used standard dose regimen is 1 mg of glucagon in adults. The solution for subcutaneous injection will be prepared by the study personnel according to the attached package leaflet.; Diagnostic test: Placebo; As placebo 1 ml sodium chloride (NaCl) 0.9% to inject subcutaneous is used. It has the same optical appearance as glucagon.
Experimental: study part 2: adult patients with primary polydipsia or central diabetes insipidus; If results of study part 1 suggest that glucagon stimulates copeptin (proof of concept),10 patients with primary polydipsia and 10 patients with central diabetes insipidus will be additionally included (study part 2): The half of the study group will start with test day A (injection of glucagon), followed by test day B (injection of placebo) and the other half will start with test day B (injection of placebo), followed by test day A (injection of glucagon).	Diagnostic test: Glucagon; Glucagon with the empirical formula of C153H225N43O49S, and a molecular weight of 3483 g/mol, is a single-chain polypeptide containing 29 amino acid residues. Glucagon is provided in a single dose vial as powder. One container contains 1 mg of glucagon which results in a concentration of 1 mg/ml after dissolution in a volume of 1 ml (Glucagen NovoNordisk (Hypokit)). The currently used standard dose regimen is 1 mg of glucagon in adults. The solution for subcutaneous injection will be prepared by the study personnel according to the attached package leaflet.; Diagnostic test: Placebo; As placebo 1 ml sodium chloride (NaCl) 0.9% to inject subcutaneous is used. It has the same optical appearance as glucagon.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal increase in copeptin level	Maximal increase in copeptin level within three hours after the injection of a single subcutaneous dose of 1mg glucagon or 0.9% NaCl. That is the difference between the maximal copeptin value measured between 30 and 180 minutes after the injection and the baseline value. measured before the injection.	Within three hours after the injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in copeptin values	Change in copeptin values	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Maximum copeptin time: the time from baseline to the maximum copeptin value	Maximum copeptin time: the time from baseline to the maximum copeptin value	Within three hours after the injection
Change in growth hormone (GH)	Change in growth hormone (GH)	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Change in prolactin	Change in prolactin	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Change in plasma sodium	Change in plasma sodium	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Change in plasma osmolality	Change in plasma osmolality	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Change in oxytocin	Change in oxytocin	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Maximal Change in GH	Maximal Change in GH	Within three hours after the injection
Maximal Change in prolactin	Maximal Change in prolactin	Within three hours after the injection
Maximal Change in plasma osmolality	Maximal Change in plasma osmolality	Within three hours after the injection
Maximal Change in oxytocin	Maximal Change in oxytocin	Within three hours after the injection

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Swiss National Science Foundation
• Investigators: Principal Investigator: Mirjam Christ-Crain, Prof. Dr. med., Endocrinology, Diabetes and Metabolism, University Hospital Basel

Publications and helpful links

Helpful Links

• Glucagon-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a double-blind, randomized, placebo-controlled study

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2020
• Primary Completion (Actual): May 30, 2021
• Study Completion (Actual): May 30, 2021

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Glucagon; Copeptin; posterior pituitary gland; polyuria-polydipsia syndrome; hypothalamo-pituitary-adrenal axis; central diabetes insipidus; primary polydipsia
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Endocrine System Diseases; Pituitary Diseases; Diabetes Insipidus; Polydipsia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon
• Other Study ID Numbers: 2020-02038; me20ChristCrain

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No