Study of Glucagon, Ghrelin and Growth Hormone as Counterregulatory Hormones

NCT ID: NCT01795235

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2014-07-31

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.

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: OTHER

Saline

Intervention Type: DRUG

Saline s.c.

Placebo

Intervention Type: DRUG

Sugar Pill

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).

Group Type: OTHER

Glucagon

Intervention Type: DRUG

Glucagon s.c.

Placebo

Intervention Type: DRUG

Sugar Pill

Saline s.c. injection and atenolol tablet

Saline s.c. injection and 100 mg atenolol tablet

Group Type: OTHER

Saline

Intervention Type: DRUG

Saline s.c.

Atenolol

Intervention Type: DRUG

Beta-1 receptor antagonist

glucagon s.c. injection and atenolol tablet

1 mg glucagon s.c. injection and 100 mg atenolol tablet

Group Type: OTHER

Glucagon

Intervention Type: DRUG

Glucagon s.c.

Atenolol

Intervention Type: DRUG

Beta-1 receptor antagonist

Interventions

Saline

Saline s.c.

Intervention Type: DRUG

Glucagon

Glucagon s.c.

Intervention Type: DRUG

Placebo

Sugar Pill

Intervention Type: DRUG

Atenolol

Beta-1 receptor antagonist

Intervention Type: DRUG

Other Intervention Names

NormalSaline; 0.9% Sodium Chloride Solution; Glucagon for injection; Tenormin

Eligibility Criteria

Inclusion Criteria

1. Healthy normal men

2. Age 18-30 yrs

3. BMI 18-27 kg/m2

Exclusion Criteria

1. Medication or previous surgery known to affect ghrelin secretion.

2. Medications known to have an impact on body weight (Seroquel, tricyclic antidepressants).

3. Medications known to have an impact on the beta adrenergic system.

4. 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).

5. Endocrine disorders, i.e., pheochromocytoma, adrenal insufficiency

6. Hematocrit < 41% men

7. History of daily tobacco use within past 3 months

8. Chronic alcohol abuse by history

9. Weight not stable (more than 10% weight change or more over past 6 months)

10. Strenuous exercise for average of more than 60 min/day

11. Investigational drug within past 6 weeks

12. Psychiatric history especially eating disorders

13. Transmeridian travel within 2 weeks prior to or during study

14. Known hypersensitivity to beta-blockers

15. Estimated Glomerular Filtration Rate below 60 mL/min/1.73m2.

16. Known cardiac dysrhythmia, especially first degree heart block. -

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Michael Thorner, MD

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael O Thorner

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ralf Nass, MD

Role: CONTACT

rmn9a@virginia.edu

Facility Contacts

Ralf Nass, MD

Role: primary

rmn9a@virginia.edu

Other Identifiers

16391

Identifier Type: -

Identifier Source: org_study_id