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To further understand the tolerability of glucagon.
To determine the tolerability of glucagon infusion administered in an escalating step-wise manner in healthy obese subjects
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glucagon Infusion | Experimental | Glucagon infusion in escalating manner at 12.5, 25, 37.5 and 50 ng/kg/min (each step for 60 min). At 30 and 60 mins of each infusion rate, we will administer a previously established questionnaire to assess overall nausea intensity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glucagon | Drug | Glucagon infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Measure glucagon tolerance in healthy obese subject prior to subject becoming significantly nauseous. | Glucagon infused in escalating manner. Each dose administered for 60 minutes. Intensity of nausea measured by administering a questionnaire that measures overall nausea intensity. | Visit 1, measured at 30 minutes |
| Measure glucagon tolerance in healthy obese subject prior to subject becoming significantly nauseous. | Glucagon infused in escalating manner. Each dose administered for 60 minutes. Intensity of nausea measured by administering a questionnaire that measures overall nausea intensity. | Visit 1, measured at 60 minutes |
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Inclusion Criteria:
Exclusion Criteria:
Treatment with any medication known to significantly impact body weight (e.g., weight loss medications, atypical antipsychotics) within 3 months prior to screening except for stable physiological hormone replacement therapy (i.e., thyroid hormone, estrogen)
History of bariatric surgery
Current liver, renal, pulmonary, cardiac, oncologic, metabolic, gastrointestinal or hematologic disease which the Investigator believes is clinically significant, including:
Self-reported history of hepatitis B, hepatitis C, or HIV
History of recurrent sleep disturbances and/or prone to sleep disturbances based on lifestyle or employment (e.g., variable work schedule, overnight shift work, etc.)
Diagnosis of sleep apnea with or without use of (continuous positive airway pressure)
Major surgery within last 3 months
Blood donation within 4 weeks prior to the screening visit
Participation in another investigational trial within 4 weeks prior to the 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 (AE) related to trial drug to the screening visit of the current trial.
Illicit drug abuse or use of nicotine-containing products within 3 months prior to the screening visit
Poor intravenous access
Blood pressure less than 100/50 mm Hg or greater than or equal to 160/100 mm Hg at screening visit
Heart rate greater than or equal to 100 beats/min at screening visit
Fasting plasma glucose <60 mg/dL or ≥126 mg/dL at screening visit
Translational Research Institute (TRI) staff member or immediate relative of TRI staff member, directly involved with this study
History of any illness or condition that, in the opinion of the study investigator, might confound the results of the study or poses an additional risk to the subject by study participation
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| Name | Affiliation | Role |
|---|---|---|
| Lauren Sparks, PhD | Prinicipal Investigator | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Translational Research Institute for Metabolism and Diabetes | Orlando | Florida | 32804 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19853906 | Background | 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. | |
| 10757621 |
| Label | URL |
|---|---|
| Florida Hospital Translational Research Institute for Metabolism and Diabetes | View source |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D005934 | Glucagon |
| ID | Term |
|---|---|
| D052336 | Proglucagon |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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| 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. |
| 22166985 | 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. |
| 13480952 | 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. |
| 2881943 | 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. |
| 8052138 | 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. |
| 26434748 | Background | Salem V, Izzi-Engbeaya C, Coello C, Thomas DB, Chambers ES, Comninos AN, Buckley A, Win Z, Al-Nahhas A, Rabiner EA, Gunn RN, Budge H, Symonds ME, Bloom SR, Tan TM, Dhillo WS. Glucagon increases energy expenditure independently of brown adipose tissue activation in humans. Diabetes Obes Metab. 2016 Jan;18(1):72-81. doi: 10.1111/dom.12585. Epub 2015 Nov 20. |
| 4042058 | Background | Melzack R, Rosberger Z, Hollingsworth ML, Thirlwell M. New approaches to measuring nausea. CMAJ. 1985 Oct 15;133(8):755-8, 761. |
| 23248172 | 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. |
| 3284915 | 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. |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |