Clinical trial NCT04550520: Copeptin After a Subcutaneous Stimulation With Glucagon in Adults
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
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Insipidus
Keywords: Copeptin
Glucagon
central diabetes insipidus
primary polydipsia
hypothalamo-pituitary-adrenal axis
posterior pituitary gland
polyuria-polydipsia syndrome
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Swiss National Science Foundation
First posted: 2020-09-16
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Maximal increase in copeptin level
timeFrame: Within three hours after the injection
Secondary outcomes:
measure: Change in copeptin values
timeFrame: Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
measure: Maximum copeptin time: the time from baseline to the maximum copeptin value
timeFrame: Within three hours after the injection
measure: Change in growth hormone (GH)
timeFrame: Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
measure: Change in prolactin
timeFrame: Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
measure: Change in plasma sodium
timeFrame: Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
measure: Change in plasma osmolality
timeFrame: Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
measure: Change in oxytocin
timeFrame: Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection
measure: Maximal Change in GH
timeFrame: Within three hours after the injection
measure: Maximal Change in prolactin
timeFrame: Within three hours after the injection
measure: Maximal Change in plasma osmolality
timeFrame: Within three hours after the injection
measure: Maximal Change in oxytocin
timeFrame: Within three hours after the injection
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Divison of Endocrinology, Diabetes and Metabolism,University Hospital Basel
Study officials:
affiliation: Endocrinology, Diabetes and Metabolism, University Hospital Basel
name: Mirjam Christ-Crain, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: