Stimulation Test With Intranasal Glucagon for Corticotroph, Somatotroph and Antidiuretic Axes

Status

Completed

Phase

Phase 4

Enrollment

10 participants (actual)

Sponsor

A.O.U. Città della Salute e della Scienza · Other

Design

Randomized · Quadruple masking

Countries

1 country

Italy

Start

1 Oct 2021

Primary completion

31 Dec 2021

Completion

31 Dec 2021

First posted

25 Jan 2022

Last update posted

25 Jan 2022

Conditions

Hypopituitarism

The diagnosis of secondary hypoadrenalism and GH deficiency (GHD) often requires the performance of a dynamic test. The glucagon stimulation test (GST) is one of the options for evaluating hypothalamic-pituitary function, representing a stimulus for both the corticotropic and somatotropic axis, substantially safe and easily available. The standard procedure involves the intramuscular injection of 1-1.5 mg of glucagon based on the patient's weight. In addition to its antero-pituitary function, glucagon has also shown its ability to stimulate neurohypophyseal secretion. Using the copeptin dosage, it has been shown that after the administration of glucagon in healthy subjects there is a significant release of ADH. However, the available data are scarse and there is no standardized protocol for the use of the glucagon test in diabetes insipidus. At the moment, GST is not the most frequently chosen diagnostic option. In fact, despite having the advantage of being able to investigate different areas of anterohypophyseal and probably posterohypophyseal function at the same time, the test has some disadvantages: the prolonged duration makes the procedure challenging, the intramuscular injection can be unwelcome, and many variables can come into play in the definition of a normal response (age, BMI, glycemic status). The recent introduction of a single-dose nasal powder formulation (Baqsimi®) could overcome some of the limitations of classic GST and make the procedure less demanding. To date, no assessments are yet available regarding a purely diagnostic role in the context of hypopituitarism of this new formulation. Through the knowledge of the physiological response of the adrenocortical, somatotropic and ADH axis to the administration of intranasal glucagon in healthy subjects, it will be possible to evaluate its possible application in the diagnosis of GH deficiency, central adrenal insufficiency and possibly diabetes insipidus.

• Experimental

  Intranasal Administration of Glucagon

  Intranasal administration of glucagon in healthy subjects

• Placebo comparator

  Intranasal Administration of Placebo

  Intranasal administration of placebo (isotonic saline solution) in healthy subjects

1. Change in serum ACTH levels between baseline and 15 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 15 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 15 minutes from glucagon/placebo administration.

2. Change in serum ACTH levels between baseline and 30 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 30 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 30 minutes from glucagon/placebo administration.

3. Change in serum ACTH levels between baseline and 45 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 45 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 45 minutes from glucagon/placebo administration.

4. Change in serum ACTH levels between baseline and 60 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 60 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 60 minutes from glucagon/placebo administration.

5. Change in serum ACTH levels between baseline and 75 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 75 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 75 minutes from glucagon/placebo administration.

6. Change in serum ACTH levels between baseline and 90 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 90 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 90 minutes from glucagon/placebo administration.

7. Change in serum ACTH levels between baseline and 120 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 120 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 120 minutes from glucagon/placebo administration.

8. Change in serum ACTH levels between baseline and 150 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 150 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 150 minutes from glucagon/placebo administration.

9. Change in serum ACTH levels between baseline and 180 minutes after glucagon/placebo administration

   Time frame · From baseline (0 minutes) to 180 minutes after glucagon/placebo administration

   Registry description

   The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum ACTH (ng/L) at baseline (0 minutes) and after 180 minutes from glucagon/placebo administration.

10. Change in serum cortisol levels between baseline and 15 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 15 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 15 minutes from glucagon/placebo administration.

11. Change in serum cortisol levels between baseline and 30 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 30 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 30 minutes from glucagon/placebo administration.

12. Change in serum cortisol levels between baseline and 45 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 45 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 45 minutes from glucagon/placebo administration.

13. Change in serum cortisol levels between baseline and 60 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 60 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 60 minutes from glucagon/placebo administration.

14. Change in serum cortisol levels between baseline and 75 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 75 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 75 minutes from glucagon/placebo administration.

15. Change in serum cortisol levels between baseline and 90 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 90 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 90 minutes from glucagon/placebo administration.

16. Change in serum cortisol levels between baseline and 120 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 120 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 120 minutes from glucagon/placebo administration.

17. Change in serum cortisol levels between baseline and 150 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 150 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 150 minutes from glucagon/placebo administration.

18. Change in serum cortisol levels between baseline and 180 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 180 minutes after glucagon/placebo administration

    Registry description

    The response of the corticotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum cortisol (µg/L) at baseline (0 minutes) and after 180 minutes from glucagon/placebo administration.

19. Change in serum GH levels between baseline and 15 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 15 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 15 minutes from glucagon/placebo administration.

20. Change in serum GH levels between baseline and 30 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 30 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 30 minutes from glucagon/placebo administration.

21. Change in serum GH levels between baseline and 45 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 45 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 45 minutes from glucagon/placebo administration.

22. Change in serum GH levels between baseline and 60 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 60 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 60 minutes from glucagon/placebo administration.

23. Change in serum GH levels between baseline and 75 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 75 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 75 minutes from glucagon/placebo administration.

24. Change in serum GH levels between baseline and 90 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 90 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 90 minutes from glucagon/placebo administration.

25. Change in serum GH levels between baseline and 120 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 120 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 120 minutes from glucagon/placebo administration.

26. Change in serum GH levels between baseline and 150 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 150 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 150 minutes from glucagon/placebo administration.

27. Change in serum GH levels between baseline and 180 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 180 minutes after glucagon/placebo administration

    Registry description

    The response of the somatotroph axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring serum GH (µg/L) at baseline (0 minutes) and after 180 minutes from glucagon/placebo administration.

28. Change in plasma copeptin levels between baseline and 15 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 15 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 15 minutes from glucagon/placebo administration.

29. Change in plasma copeptin levels between baseline and 30 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 30 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 30 minutes from glucagon/placebo administration.

30. Change in plasma copeptin levels between baseline and 45 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 45 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 45 minutes from glucagon/placebo administration.

31. Change in plasma copeptin levels between baseline and 60 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 60 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 60 minutes from glucagon/placebo administration.

32. Change in plasma copeptin levels between baseline and 75 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 75 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 75 minutes from glucagon/placebo administration.

33. Change in plasma copeptin levels between baseline and 90 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 90 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 90 minutes from glucagon/placebo administration.

34. Change in plasma copeptin levels between baseline and 120 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 120 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 120 minutes from glucagon/placebo administration.

35. Change in plasma copeptin levels between baseline and 150 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 150 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 150 minutes from glucagon/placebo administration.

36. Change in plasma copeptin levels between baseline and 180 minutes after glucagon/placebo administration

    Time frame · From baseline (0 minutes) to 180 minutes after glucagon/placebo administration

    Registry description

    The response of the antidiuretic axis to the administration of intranasal glucagon, compared to placebo, was evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 180 minutes from glucagon/placebo administration.