Effects of Glucagon Administration on Energy Expenditure

NCT02237053 | Completed Phase 1 DMC

• 1 other identifier: TRIMDFH 601205
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to collect data to help researchers better understand the effects of glucagon on the amount of calories burned.

Conditions

Hyperglucagonemia; Obesity

Keywords

Energy expenditure; Glucagon; Octreotide; Weight loss

Outcome Measures

Primary Outcomes (1)

• Measure of energy expenditure

  Energy expenditure (and respiratory quotient) will be measured within the small calorimeter rooms. Oxygen and carbon dioxide levels in the chambers will be measured.

  Day 2, Day 9, Day 16

Secondary Outcomes (1)

• Measure of endogenous glucose production

  Day 3, Day 10, Day 17

Study Arms (3)

Glucagon with Octreotide and insulin

ACTIVE COMPARATOR

Overnight (10 hours) infusion of glucagon, then 3 hours infusion of glucagon with concurrent infusions of Octreotide and insulin.

Drug: Glucagon; Drug: Octreotide; Drug: Insulin

Placebo, Glucagon with Octreotide and Insulin

PLACEBO COMPARATOR

Overnight (10 hours) infusion of saline, then 3 hour infusion of glucagon with concurrent infusions of Octreotide and insulin.

Drug: Glucagon; Drug: Octreotide; Behavioral: Placebo; Drug: Insulin

Placebo, with Octreotide and insulin

PLACEBO COMPARATOR

Overnight (10 hours) infusion of saline, then 3 hour infusion of saline with concurrent infusions of Octreotide and insulin.

Drug: Octreotide; Behavioral: Placebo; Drug: Insulin

Interventions

Glucagon DRUG

Glucagon with Octreotide and insulin; Placebo, Glucagon with Octreotide and Insulin

Octreotide DRUG

Also known as: Sandostatin

Glucagon with Octreotide and insulin; Placebo, Glucagon with Octreotide and Insulin; Placebo, with Octreotide and insulin

Placebo BEHAVIORAL

Also known as: Saline

Placebo, Glucagon with Octreotide and Insulin; Placebo, with Octreotide and insulin

Insulin DRUG

Also known as: Hypoglycemic agent

Glucagon with Octreotide and insulin; Placebo, Glucagon with Octreotide and Insulin; Placebo, with Octreotide and insulin

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject is a male between the ages of 18 and 50 years.
• Subject has a body mass index (BMI) less than or equal to 26 kg/m2. BMI = weight (kg)/height (m) and body weight greater than or equal to 50 kg at the pre-study (screening) visit
• Subject has been weight stable over the last 3 months (plus or minus 3 kg)
• Subject is judged to be non-diabetic and in good health on the basis of medical history, physical examination, electrocardiogram, and routine laboratory data.
• Subject understands the procedures and agrees to participate in the study program by giving written informed consent, and is willing to comply with the trial restrictions.
• Subject is willing to avoid alcohol consumption for 48 hours prior to each period.
• Subject is willing to avoid strenuous physical activity (i.e., strenuous or unaccustomed weight lifting, running, bicycling, etc.) beginning 72 hours prior to first drug administration period and for the duration of the study.
• Subject is willing to avoid consumption of caffeine and caffeinated beverages for 24 hours prior to drug administration in each period. Subject is willing to consume no more than 2 caffeinated beverages per day during all other parts of the study.

You may not qualify if:

• is mentally or legally incapacitated, has significant emotional problems at the time of pretrial (screening) visit or expected during the conduct of the trial or has a history of clinically significant psychiatric disorder of the last 5 years. Subjects who have had situational depression may be enrolled in the trial at the discretion of the investigator.
• has a history of clinically significant endocrine (including type 1 or type 2, or steroid-induced diabetes), gastrointestinal (including prior history of pancreatitis), cardiovascular (including hypertension, angina, coronary artery disease, valvular disease, heart rate or rhythm abnormalities), hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological (including stroke and chronic seizures) abnormalities or diseases. Subjects with a history of uncomplicated kidney stones or childhood asthma may be enrolled in the trial at the discretion of the investigator.
• has a known history of any endocrine tumors (e.g. pheochromocytoma, glucagonoma, or insulinoma, etc.)
• has a clinically significant abnormality on screening ECG or evidence or a history of myocardial ischemia, atrioventricular block, Wolf-Parkinson-White syndrome or other conduction abnormality. Subjects having any clinically significant ECG abnormality at screening may be included at the discretion of the PI.
• has a fasting blood glucose (FPG) less than or equal to 65 mg/dL or greater than or equal to 100 mg/dL on the pre-study screening labs.
• has impaired kidney or liver function, as evidenced by screening blood work.
• has irritable bowel disease, or recurrent occurrences of nausea, vomiting, diarrhea, constipation or abdominal pain.
• has a history of any illness that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• has an estimated creatinine clearance of ≤80 mL/min based on the Cockcroft-Gault equation
• has a history of neoplastic disease
• has a history of significant multiple and/or severe allergies (e.g. food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food; or allergy/intolerability to insulin, glucagon, or octreotide.
• is positive for hepatitis B surface antigen, hepatitis C antibodies, or HIV
• had major surgery within 3 months, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit.
• has participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit. The 4 week window will be derived from the date of the last trial medication and / or blood collection in a previous trial and/or adverse event related to trial drug to the pretrial/screening visit of the current trial.
• consumes greater than 2 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[354 mL/12 ounces\], wine \[118 mL/4 ounces\], or distilled spirits \[29.5 mL/1 ounce\]) per day. Patients that consume 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator.

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

Florida Hospital Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (13)

• Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009 Nov 7;374(9701):1606-16. doi: 10.1016/S0140-6736(09)61375-1. Epub 2009 Oct 23.

  PMID: 19853906 BACKGROUND

• Flint A, Raben A, Rehfeld JF, Holst JJ, Astrup A. The effect of glucagon-like peptide-1 on energy expenditure and substrate metabolism in humans. Int J Obes Relat Metab Disord. 2000 Mar;24(3):288-98. doi: 10.1038/sj.ijo.0801126.

  PMID: 10757621 BACKGROUND

• Cryer PE. Minireview: Glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology. 2012 Mar;153(3):1039-48. doi: 10.1210/en.2011-1499. Epub 2011 Dec 13.

  PMID: 22166985 BACKGROUND

• SCHULMAN JL, CARLETON JL, WHITNEY G, WHITEHORN JC. Effect of glucagon on food intake and body weight in man. J Appl Physiol. 1957 Nov;11(3):419-21. doi: 10.1152/jappl.1957.11.3.419. No abstract available.

  PMID: 13480952 BACKGROUND

• Nair KS. Hyperglucagonemia increases resting metabolic rate in man during insulin deficiency. J Clin Endocrinol Metab. 1987 May;64(5):896-901. doi: 10.1210/jcem-64-5-896.

  PMID: 2881943 BACKGROUND

• Calles-Escandon J. Insulin dissociates hepatic glucose cycling and glucagon-induced thermogenesis in man. Metabolism. 1994 Aug;43(8):1000-5. doi: 10.1016/0026-0495(94)90180-5.

  PMID: 8052138 BACKGROUND

• Miyoshi H, Shulman GI, Peters EJ, Wolfe MH, Elahi D, Wolfe RR. Hormonal control of substrate cycling in humans. J Clin Invest. 1988 May;81(5):1545-55. doi: 10.1172/JCI113487.

  PMID: 3284915 BACKGROUND

• Billington CJ, Briggs JE, Link JG, Levine AS. Glucagon in physiological concentrations stimulates brown fat thermogenesis in vivo. Am J Physiol. 1991 Aug;261(2 Pt 2):R501-7. doi: 10.1152/ajpregu.1991.261.2.R501.

  PMID: 1877708 BACKGROUND

• Gimeno RE, Moller DE. FGF21-based pharmacotherapy--potential utility for metabolic disorders. Trends Endocrinol Metab. 2014 Jun;25(6):303-11. doi: 10.1016/j.tem.2014.03.001. Epub 2014 Apr 5.

  PMID: 24709036 BACKGROUND

• Boyle PJ, Justice K, Krentz AJ, Nagy RJ, Schade DS. Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses. J Clin Endocrinol Metab. 1993 Mar;76(3):752-6. doi: 10.1210/jcem.76.3.8445035.

  PMID: 8445035 BACKGROUND

• Krentz AJ, Boyle PJ, Macdonald LM, Schade DS. Octreotide: a long-acting inhibitor of endogenous hormone secretion for human metabolic investigations. Metabolism. 1994 Jan;43(1):24-31. doi: 10.1016/0026-0495(94)90153-8.

  PMID: 8289671 BACKGROUND

• Tan TM, Field BC, McCullough KA, Troke RC, Chambers ES, Salem V, Gonzalez Maffe J, Baynes KC, De Silva A, Viardot A, Alsafi A, Frost GS, Ghatei MA, Bloom SR. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes. 2013 Apr;62(4):1131-8. doi: 10.2337/db12-0797. Epub 2012 Dec 17.

  PMID: 23248172 BACKGROUND

• Lam YY, Redman LM, Smith SR, Bray GA, Greenway FL, Johannsen D, Ravussin E. Determinants of sedentary 24-h energy expenditure: equations for energy prescription and adjustment in a respiratory chamber. Am J Clin Nutr. 2014 Apr;99(4):834-42. doi: 10.3945/ajcn.113.079566. Epub 2014 Feb 5.

  PMID: 24500151 BACKGROUND

Related Links

• Florida Hospital Translational Research Institute for Metabolism and Diabetes

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Glucagon; Octreotide; Sodium Chloride; Insulin; Hypoglycemic Agents

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Proinsulin; Insulins; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Christian Meyer, MD

  Translational Research Institute for Metabolism and Diabetes

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: September 11, 2014
• Study Start: September 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2016
• Last Updated: April 26, 2018

Record last verified: 2018-04

Locations

US (1)