Copeptin After a Subcutaneous Stimulation With Glucagon in Adults

Diabetes Insipidus Clinical Trial

— Glucacop  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04550520
• Other study ID #: 2020-02038; me20ChristCrain
• Status: Completed
• Phase: N/A
• Start date: September 28, 2020
• Est. completion date: May 30, 2021

Study information

• Verified date: May 2022
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 30, 2021
• Est. primary completion date: May 30, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Insipidus
• Polydipsia

Intervention

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.
• Placebo
As placebo 1 ml sodium chloride (NaCl) 0.9% to inject subcutaneous is used. It has the same optical appearance as glucagon.

Locations

Country	Name	City	State
Switzerland	Divison of Endocrinology, Diabetes and Metabolism,University Hospital Basel	Basel

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Swiss National Science Foundation

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in copeptin values	Change in copeptin values	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Secondary	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
Secondary	Change in growth hormone (GH)	Change in growth hormone (GH)	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Secondary	Change in prolactin	Change in prolactin	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Secondary	Change in plasma sodium	Change in plasma sodium	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Secondary	Change in plasma osmolality	Change in plasma osmolality	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Secondary	Change in oxytocin	Change in oxytocin	Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Secondary	Maximal Change in GH	Maximal Change in GH	Within three hours after the injection
Secondary	Maximal Change in prolactin	Maximal Change in prolactin	Within three hours after the injection
Secondary	Maximal Change in plasma osmolality	Maximal Change in plasma osmolality	Within three hours after the injection
Secondary	Maximal Change in oxytocin	Maximal Change in oxytocin	Within three hours after the injection

External Links

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