Study of Glucagon, Ghrelin and Growth Hormone as Counterregulatory Hormones

Sponsor

University of Virginia (Other)

Overall Status

Unknown status

CT.gov ID

NCT01795235

Collaborator

Novo Nordisk A/S (Industry)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Saline Drug: Glucagon Drug: Placebo Drug: Atenolol	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

Glucagon, Ghrelin and Growth Hormone as Counterregulatory Hormones

Study Start Date :

Dec 1, 2012

Anticipated Primary Completion Date :

Jul 1, 2014

Anticipated Study Completion Date :

Jul 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Circulating acyl-ghrelin concentration after glucagon stimulation with and without beta-adrenergic blockade [18 months]

Secondary Outcome Measures

Association between circulating acyl-ghrelin concentration and GH and cortisol after glucagon administration with and without beta-adrenergic blockade [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 30 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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. -

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Virginia	Charlottesville	Virginia	United States	22902

Sponsors and Collaborators

University of Virginia
Novo Nordisk A/S

Investigators

Principal Investigator: Michael O Thorner, University of Virginia

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Michael Thorner, MD, MD, University of Virginia

ClinicalTrials.gov Identifier:

NCT01795235

Other Study ID Numbers:

16391

First Posted:

Feb 20, 2013

Last Update Posted:

Feb 20, 2013

Last Verified:

Feb 1, 2013

Keywords provided by Michael Thorner, MD, MD, University of Virginia

men

Additional relevant MeSH terms:

Atenolol

Glucagon

Glucagon-Like Peptide 1

Study Results

No Results Posted as of Feb 20, 2013