Clinical trial NCT05206149: Stimulation Test With Intranasal Glucagon for Corticotroph, Somatotroph and Antidiuretic Axes
Official title: Stimulation Test With Intranasal Glucagon for Corticotroph, Somatotroph and Antidiuretic Axes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypopituitarism
Lead sponsor: A.O.U. Città della Salute e della Scienza
Sponsor class: OTHER
First posted: 2022-01-25
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

- Any adult healthy subject (age \>= 18 years old) and not meeting the exclusion criteria listed below

Exclusion Criteria:

* BMI \< 18.5 kg/m2 or \> 25 kg/m2
* Any active pharmacological treatment
* Pregnancy or breastfeeding

Primary outcomes:
measure: Change in serum ACTH levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in serum ACTH levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in serum cortisol levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in serum GH levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in plasma copeptin levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
Secondary outcomes:
measure: Change in serum sodium levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in serum sodium levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in serum potassium levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in plasma osmolality between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in serum glucose levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 15 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 30 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 45 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 60 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 75 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 90 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 120 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 150 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
measure: Change in plasma insulin levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in urine sodium levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in urine potassium levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in urine creatinine levels between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in urine osmolality between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in resistance at bioimpedance vector analysis between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in reactance at bioimpedance vector analysis between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
measure: Change in phase angle at bioimpedance vector analysis between baseline and 180 minutes after glucagon/placebo administration
timeFrame: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
Other outcomes:
Locations:
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza
state: Piemonte
Study officials:
References:
citation: Boguszewski CL. Glucagon stimulation test: has its time come? Endocrine. 2017 Sep;57(3):361-363. doi: 10.1007/s12020-017-1356-8. Epub 2017 Jun 23. No abstract available.
citation: Arvat E, Maccagno B, Ramunni J, Giordano R, Broglio F, Gianotti L, Maccario M, Camanni F, Ghigo E. Interaction between glucagon and hexarelin, a peptidyl GH secretagogue, on somatotroph and corticotroph secretion in humans. Eur J Endocrinol. 2000 Nov;143(5):601-6. doi: 10.1530/eje.0.1430601.
citation: Berg C, Meinel T, Lahner H, Yuece A, Mann K, Petersenn S. Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery. Eur J Endocrinol. 2010 Mar;162(3):477-82. doi: 10.1530/EJE-09-0824. Epub 2009 Dec 8.
citation: Yuen KC, Biller BM, Katznelson L, Rhoads SA, Gurel MH, Chu O, Corazzini V, Spiller K, Gordon MB, Salvatori R, Cook DM. Clinical characteristics, timing of peak responses and safety aspects of two dosing regimens of the glucagon stimulation test in evaluating growth hormone and cortisol secretion in adults. Pituitary. 2013 Jun;16(2):220-30. doi: 10.1007/s11102-012-0407-7.
citation: Giuffrida FM, Berger K, Monte L, Oliveira CH, Hoff AO, Maciel RM, Vieira JG. Relationship between GH response and glycemic fluctuations in the glucagon stimulation test. Growth Horm IGF Res. 2009 Feb;19(1):77-81. doi: 10.1016/j.ghir.2008.06.002. Epub 2008 Aug 3.
citation: Dichtel LE, Yuen KC, Bredella MA, Gerweck AV, Russell BM, Riccio AD, Gurel MH, Sluss PM, Biller BM, Miller KK. Overweight/Obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency. J Clin Endocrinol Metab. 2014 Dec;99(12):4712-9. doi: 10.1210/jc.2014-2830.
citation: Hamrahian AH, Yuen KC, Gordon MB, Pulaski-Liebert KJ, Bena J, Biller BM. Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitary-adrenal axes in adults: results from a prospective randomized multicenter study. Pituitary. 2016 Jun;19(3):332-41. doi: 10.1007/s11102-016-0712-7.
citation: Lewandowski KC, Lewinski A, Skowronska-Jozwiak E, Stasiak M, Horzelski W, Brabant G. Copeptin under glucagon stimulation. Endocrine. 2016 May;52(2):344-51. doi: 10.1007/s12020-015-0783-7. Epub 2015 Nov 17.
citation: Guzman CB, Dulude H, Piche C, Rufiange M, Sadoune AA, Rampakakis E, Carballo D, Triest M, Zhang MX, Zhang S, Tafreshi M, Sicard E. Effects of common cold and concomitant administration of nasal decongestant on the pharmacokinetics and pharmacodynamics of nasal glucagon in otherwise healthy participants: A randomized clinical trial. Diabetes Obes Metab. 2018 Mar;20(3):646-653. doi: 10.1111/dom.13134. Epub 2017 Nov 19.
citation: Sherr JL, Ruedy KJ, Foster NC, Piche CA, Dulude H, Rickels MR, Tamborlane WV, Bethin KE, DiMeglio LA, Fox LA, Wadwa RP, Schatz DA, Nathan BM, Marcovina SM, Rampakakis E, Meng L, Beck RW; T1D Exchange Intranasal Glucagon Investigators. Glucagon Nasal Powder: A Promising Alternative to Intramuscular Glucagon in Youth With Type 1 Diabetes. Diabetes Care. 2016 Apr;39(4):555-62. doi: 10.2337/dc15-1606. Epub 2016 Feb 16.