Copeptin After a Subcutaneous Stimulation With Glucagon in Adults

NCT ID: NCT04550520

Last Updated: 2022-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-28
• Study Completion Date: 2021-05-30

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.

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.

Conditions

Diabetes Insipidus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Glucagon

Intervention Type: DIAGNOSTIC_TEST

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

Intervention Type: DIAGNOSTIC_TEST

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

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).

Group Type: EXPERIMENTAL

Glucagon

Intervention Type: DIAGNOSTIC_TEST

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

Intervention Type: DIAGNOSTIC_TEST

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

Interventions

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.

Intervention Type: 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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• no medication except hormonal contraception

• 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

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Swiss National Science Foundation

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mirjam Christ-Crain, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Endocrinology, Diabetes and Metabolism, University Hospital Basel

Locations

Divison of Endocrinology, Diabetes and Metabolism,University Hospital Basel

Basel, , Switzerland

Countries

Switzerland

Other Identifiers

2020-02038; me20ChristCrain

Identifier Type: -

Identifier Source: org_study_id