Study of Glucagon, Ghrelin and Growth Hormone as Counterregulatory Hormones

Study Overview
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Brief Summary
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Glucagon has been used for decades as a test of growth hormone (GH) reserve. The pathway by which GH is stimulated by glucagon is not established. Acyl ghrelin has been shown to increase GH levels and to be stimulated by an increase in adrenergic activity. The proposed study will test the concept that with the fall in blood glucose it is likely that there is a sympathetic discharge which contributes to the increase in acyl ghrelin and indirectly leads to the increase in GH and cortisol.

Detailed Description
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Glucagon given to healthy adults in doses of 1-1.5 mg i.m. has been shown to result in a peak glucagon level in the circulation after 30 min, followed by an increase in glucose and insulin levels. The subsequent decline in glucose, insulin and glucagon was followed by an increase in cortisol and GH. Ghrelin is a 28 amino acid peptide which is released from the fundus of the stomach, within the oxyntic glands and the small intestine. It circulates in two major forms, acylated and des-acylated ghrelin. Acylated ghrelin has strong GH-releasing effects which are mediated via the G-protein coupled ghrelin receptor. The proposed study will test the concept that with the fall in blood glucose during a glucagon test it is likely that there is a sympathetic discharge which contributes to the increase in acyl ghrelin and indirectly leads to the increase in GH and cortisol.

Official Title
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Glucagon, Ghrelin and Growth Hormone as Counterregulatory Hormones

Conditions
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Healthy

Intervention / Treatment
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* Drug: Saline
* Drug: Glucagon
* Drug: Placebo
* Drug: Atenolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy normal men Age 18-30 yrs BMI 18-27 kg/m2 Exclusion Criteria: Medication or previous surgery known to affect ghrelin secretion. Medications known to have an impact on body weight (Seroquel, tricyclic antidepressants). Medications known to have an impact on the beta adrenergic system. Coronary artery disease, congestive heart failure, peripheral vascular disease, diabetes mellitus, significant hypertension (BP >180 systolic or >100 diastolic at rest); renal, hepatic, pulmonary disease; untreated hypothyroidism, untreated hyperthyroidism; history of seizure disorder; history of malignancy (other than some skin cancers), history of active chronic infections (e.g., HIV, tuberculosis). Endocrine disorders, i.e., pheochromocytoma, adrenal insufficiency Hematocrit < 41% men History of daily tobacco use within past 3 months Chronic alcohol abuse by history Weight not stable (more than 10% weight change or more over past 6 months) Strenuous exercise for average of more than 60 min/day Investigational drug within past 6 weeks Psychiatric history especially eating disorders Transmeridian travel within 2 weeks prior to or during study Known hypersensitivity to beta-blockers Estimated Glomerular Filtration Rate below 60 mL/min/1.73m2. Known cardiac dysrhythmia, especially first degree heart block. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Saline s.c. injection and placebo tablet<br>Saline s.c. injection and one placebo tablet (preceded by one placebo tablet per day at 0900h for two days before admission). | Drug: Saline<br>* Saline s.c.<br>* Other names: 0.9% Sodium Chloride Solution;Drug: Placebo<br>* Sugar Pill<br>|
| Other: glucagon s.c. injection and placebo tablet<br>1 mg glucagon s.c. injection and one placebo tablet (preceded by one placebo tablet per day at 0900h for two days before admission). | Drug: Glucagon<br>* Glucagon s.c.<br>* Other names: Glucagon for injection;Drug: Placebo<br>* Sugar Pill<br>|
| Other: Saline s.c. injection and atenolol tablet<br>Saline s.c. injection and 100 mg atenolol tablet | Drug: Saline<br>* Saline s.c.<br>* Other names: 0.9% Sodium Chloride Solution;Drug: Atenolol<br>* Beta-1 receptor antagonist<br>* Other names: Tenormin;|
| Other: glucagon s.c. injection and atenolol tablet<br>1 mg glucagon s.c. injection and 100 mg atenolol tablet | Drug: Glucagon<br>* Glucagon s.c.<br>* Other names: Glucagon for injection;Drug: Atenolol<br>* Beta-1 receptor antagonist<br>* Other names: Tenormin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating acyl-ghrelin concentration after glucagon stimulation with and without beta-adrenergic blockade |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between circulating acyl-ghrelin concentration and GH and cortisol after glucagon administration with and without beta-adrenergic blockade |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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men