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

Primary Purpose

Diabetes Insipidus

Status
Completed
Phase
Not Applicable
Locations
Switzerland
Study Type
Interventional
Intervention
Glucagon
Placebo
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Diabetes Insipidus focused on measuring Copeptin, Glucagon, central diabetes insipidus, primary polydipsia, hypothalamo-pituitary-adrenal axis, posterior pituitary gland, polyuria-polydipsia syndrome

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

study part 1: healthy adult volunteers

study part 2: adult patients with primary polydipsia or central diabetes insipidus

Arm Description

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).

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in copeptin values
Change in copeptin values
Maximum copeptin time: the time from baseline to the maximum copeptin value
Maximum copeptin time: the time from baseline to the maximum copeptin value
Change in growth hormone (GH)
Change in growth hormone (GH)
Change in prolactin
Change in prolactin
Change in plasma sodium
Change in plasma sodium
Change in plasma osmolality
Change in plasma osmolality
Change in oxytocin
Change in oxytocin
Maximal Change in GH
Maximal Change in GH
Maximal Change in prolactin
Maximal Change in prolactin
Maximal Change in plasma osmolality
Maximal Change in plasma osmolality
Maximal Change in oxytocin
Maximal Change in oxytocin

Full Information

First Posted
September 9, 2020
Last Updated
May 18, 2022
Sponsor
University Hospital, Basel, Switzerland
Collaborators
Swiss National Science Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT04550520
Brief Title
Copeptin After a Subcutaneous Stimulation With Glucagon in Adults
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
September 28, 2020 (Actual)
Primary Completion Date
May 30, 2021 (Actual)
Study Completion Date
May 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland
Collaborators
Swiss National Science Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Insipidus
Keywords
Copeptin, Glucagon, central diabetes insipidus, primary polydipsia, hypothalamo-pituitary-adrenal axis, posterior pituitary gland, polyuria-polydipsia syndrome

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
study part 1: healthy adult volunteers
Arm Type
Experimental
Arm Description
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).
Arm Title
study part 2: adult patients with primary polydipsia or central diabetes insipidus
Arm Type
Experimental
Arm Description
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).
Intervention Type
Diagnostic Test
Intervention Name(s)
Glucagon
Intervention Description
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
Intervention Name(s)
Placebo
Intervention Description
As placebo 1 ml sodium chloride (NaCl) 0.9% to inject subcutaneous is used. It has the same optical appearance as glucagon.
Primary Outcome Measure Information:
Title
Maximal increase in copeptin level
Description
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.
Time Frame
Within three hours after the injection
Secondary Outcome Measure Information:
Title
Change in copeptin values
Description
Change in copeptin values
Time Frame
Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Title
Maximum copeptin time: the time from baseline to the maximum copeptin value
Description
Maximum copeptin time: the time from baseline to the maximum copeptin value
Time Frame
Within three hours after the injection
Title
Change in growth hormone (GH)
Description
Change in growth hormone (GH)
Time Frame
Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Title
Change in prolactin
Description
Change in prolactin
Time Frame
Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Title
Change in plasma sodium
Description
Change in plasma sodium
Time Frame
Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Title
Change in plasma osmolality
Description
Change in plasma osmolality
Time Frame
Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Title
Change in oxytocin
Description
Change in oxytocin
Time Frame
Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
Title
Maximal Change in GH
Description
Maximal Change in GH
Time Frame
Within three hours after the injection
Title
Maximal Change in prolactin
Description
Maximal Change in prolactin
Time Frame
Within three hours after the injection
Title
Maximal Change in plasma osmolality
Description
Maximal Change in plasma osmolality
Time Frame
Within three hours after the injection
Title
Maximal Change in oxytocin
Description
Maximal Change in oxytocin
Time Frame
Within three hours after the injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mirjam Christ-Crain, Prof. Dr. med.
Organizational Affiliation
Endocrinology, Diabetes and Metabolism, University Hospital Basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Divison of Endocrinology, Diabetes and Metabolism,University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Links:
URL
https://doi.org/10.1530/EJE-22-0033
Description
Glucagon-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a double-blind, randomized, placebo-controlled study

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Copeptin After a Subcutaneous Stimulation With Glucagon in Adults

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