Copeptin After a Subcutaneous Stimulation With Glucagon in Adults
Condition: Diabetes Insipidus
MeSH terms: Diabetes Insipidus; Polydipsia
Study type: Interventional

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.
    

Intervention name(s): Glucagon; Placebo
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): 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.; As placebo 1 ml sodium chloride (NaCl) 0.9% to inject subcutaneous is used. It has the same optical appearance as glucagon.
Intervention MeSH terms: Glucagon
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.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Diagnostic
Keywords: Copeptin; Glucagon; central diabetes insipidus; primary polydipsia; hypothalamo-pituitary-adrenal axis; posterior pituitary gland; polyuria-polydipsia syndrome