Glucacop: Copeptin After a Subcutaneous Stimulation With Glucagon in Adults

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Completed

CT.gov ID

NCT04550520

Collaborator

Swiss National Science Foundation (Other)

Enrollment

Location

Arms

Actual Duration (Months)

5.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Insipidus	Diagnostic Test: Glucagon Diagnostic Test: Placebo	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

42 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

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. 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). The randomization will be performed by an independent third party.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. 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). The randomization will be performed by an independent third party.

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Sep 28, 2020

Actual Primary Completion Date :

May 30, 2021

Actual Study Completion Date :

May 30, 2021

Arms and Interventions

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.

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

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.

Outcome Measures

Primary Outcome Measures

Maximal increase in copeptin level [Within three hours after the injection]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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