Stimulation Test With Intranasal Glucagon for Corticotroph, Somatotroph and Antidiuretic Axes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Change in serum ACTH levels between baseline and 30 minutes after glucagon/placebo administration
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Any adult healthy subject (age >= 18 years old) and not meeting the exclusion criteria listed below
排除标准
- •BMI < 18.5 kg/m2 or > 25 kg/m2
- •Any active pharmacological treatment
- •Pregnancy or breastfeeding
研究组 & 干预措施
Intranasal Administration of Glucagon
Intranasal administration of glucagon in healthy subjects
干预措施: Intranasal glugagon (Drug)
Intranasal Administration of Placebo
Intranasal administration of placebo (isotonic saline solution) in healthy subjects
干预措施: Intranasal placebo (Drug)
结局指标
主要结局
Change in serum ACTH levels between baseline and 30 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 120 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 15 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 45 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 60 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 90 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 150 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 180 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 30 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 45 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
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.
Change in serum ACTH levels between baseline and 75 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 60 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 75 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 90 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 180 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 15 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 30 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 15 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 120 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 150 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 30 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 30 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 180 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 150 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
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.
Change in serum cortisol levels between baseline and 150 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 150 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 45 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 60 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 75 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 15 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 15 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 45 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 45 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 90 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
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.
Change in serum GH levels between baseline and 120 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 60 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 60 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 75 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 75 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 90 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 90 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 120 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 120 minutes after glucagon/placebo administration
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.
Change in plasma copeptin levels between baseline and 180 minutes after glucagon/placebo administration
时间窗: From baseline (0 minutes) to 180 minutes after glucagon/placebo administration
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.
次要结局
- Change in serum sodium levels between baseline and 75 minutes after glucagon/placebo administration(From baseline (0 minutes) to 75 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 15 minutes after glucagon/placebo administration(From baseline (0 minutes) to 15 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 150 minutes after glucagon/placebo administration(From baseline (0 minutes) to 150 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 45 minutes after glucagon/placebo administration(From baseline (0 minutes) to 45 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 60 minutes after glucagon/placebo administration(From baseline (0 minutes) to 60 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 90 minutes after glucagon/placebo administration(From baseline (0 minutes) to 90 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 30 minutes after glucagon/placebo administration(From baseline (0 minutes) to 30 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 30 minutes after glucagon/placebo administration(From baseline (0 minutes) to 30 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 150 minutes after glucagon/placebo administration(From baseline (0 minutes) to 150 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 90 minutes after glucagon/placebo administration(From baseline (0 minutes) to 90 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 120 minutes after glucagon/placebo administration(From baseline (0 minutes) to 120 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 15 minutes after glucagon/placebo administration(From baseline (0 minutes) to 15 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 45 minutes after glucagon/placebo administration(From baseline (0 minutes) to 45 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 60 minutes after glucagon/placebo administration(From baseline (0 minutes) to 60 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 150 minutes after glucagon/placebo administration(From baseline (0 minutes) to 150 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 60 minutes after glucagon/placebo administration(From baseline (0 minutes) to 60 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 90 minutes after glucagon/placebo administration(From baseline (0 minutes) to 90 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 15 minutes after glucagon/placebo administration(From baseline (0 minutes) to 15 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 15 minutes after glucagon/placebo administration(From baseline (0 minutes) to 15 minutes after glucagon/placebo administration)
- Change in serum sodium levels between baseline and 120 minutes after glucagon/placebo administration(From baseline (0 minutes) to 120 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 75 minutes after glucagon/placebo administration(From baseline (0 minutes) to 75 minutes after glucagon/placebo administration)
- Change in serum potassium levels between baseline and 150 minutes after glucagon/placebo administration(From baseline (0 minutes) to 150 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 120 minutes after glucagon/placebo administration(From baseline (0 minutes) to 120 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 120 minutes after glucagon/placebo administration(From baseline (0 minutes) to 120 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 30 minutes after glucagon/placebo administration(From baseline (0 minutes) to 30 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 45 minutes after glucagon/placebo administration(From baseline (0 minutes) to 45 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 60 minutes after glucagon/placebo administration(From baseline (0 minutes) to 60 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 75 minutes after glucagon/placebo administration(From baseline (0 minutes) to 75 minutes after glucagon/placebo administration)
- Change in plasma osmolality between baseline and 90 minutes after glucagon/placebo administration(From baseline (0 minutes) to 90 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 15 minutes after glucagon/placebo administration(From baseline (0 minutes) to 15 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 30 minutes after glucagon/placebo administration(From baseline (0 minutes) to 30 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 45 minutes after glucagon/placebo administration(From baseline (0 minutes) to 45 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 75 minutes after glucagon/placebo administration(From baseline (0 minutes) to 75 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 75 minutes after glucagon/placebo administration(From baseline (0 minutes) to 75 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 150 minutes after glucagon/placebo administration(From baseline (0 minutes) to 150 minutes after glucagon/placebo administration)
- Change in urine sodium levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in reactance at bioimpedance vector analysis between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in serum glucose levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 30 minutes after glucagon/placebo administration(From baseline (0 minutes) to 30 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 45 minutes after glucagon/placebo administration(From baseline (0 minutes) to 45 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 60 minutes after glucagon/placebo administration(From baseline (0 minutes) to 60 minutes after glucagon/placebo administration)
- Change in urine potassium levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in resistance at bioimpedance vector analysis between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 90 minutes after glucagon/placebo administration(From baseline (0 minutes) to 90 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 120 minutes after glucagon/placebo administration(From baseline (0 minutes) to 120 minutes after glucagon/placebo administration)
- Change in plasma insulin levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in urine creatinine levels between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in urine osmolality between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
- Change in phase angle at bioimpedance vector analysis between baseline and 180 minutes after glucagon/placebo administration(From baseline (0 minutes) to 180 minutes after glucagon/placebo administration)
研究者
Ezio Ghigo
Full Professor
A.O.U. Città della Salute e della Scienza