Copeptin After a Subcutaneous Stimulation With Glucagon in Adults

NCT04550520 | Completed

• 1 other identifier: 2020-02038; me20ChristCrain
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Insipidus

Keywords

Copeptin; Glucagon; central diabetes insipidus; primary polydipsia; hypothalamo-pituitary-adrenal axis; posterior pituitary gland; polyuria-polydipsia syndrome

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Change in copeptin values

  Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection

• Maximum copeptin time: the time from baseline to the maximum copeptin value

  Within three hours after the injection

• Change in growth hormone (GH)

  Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection

• Change in prolactin

  Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection

• Change in plasma sodium

  Measured at 0 (baseline), 30, 60, 90, 120, 150 and 180 minutes after injection

Study Arms (2)

study part 1: healthy adult volunteers

EXPERIMENTAL

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; Diagnostic Test: Placebo

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

EXPERIMENTAL

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

Interventions

Glucagon 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.

study part 1: healthy adult volunteers; study part 2: adult patients with primary polydipsia or central diabetes insipidus

Placebo 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 1: healthy adult volunteers; study part 2: adult patients with primary polydipsia or central diabetes insipidus

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (1)

Divison of Endocrinology, Diabetes and Metabolism,University Hospital Basel

Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Polydipsia, Psychogenic

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pituitary Diseases; Endocrine System Diseases; Polydipsia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Mirjam Christ-Crain, Prof. Dr. med.

  Endocrinology, Diabetes and Metabolism, University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: September 28, 2020
• Primary Completion: May 30, 2021
• Study Completion: May 30, 2021
• Last Updated: May 25, 2022

Record last verified: 2022-05

Locations

CH (1)