To Determine Tolerability to Glucagon Infusion in Obese Subjects

NCT02817659 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TRIMDFH 778967
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To further understand the tolerability of glucagon.

Conditions

Obesity

Keywords

Glucagon

Outcome Measures

Primary Outcomes (2)

• 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

Study Arms (1)

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.

Drug: Glucagon

Interventions

Glucagon DRUG

Glucagon infusion

Glucagon Infusion

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-55 years, inclusive
• BMI ≥27 to ≤40 kg/m2
• Stable body weight for 3 months (self-reported loss/gain \<5%)
• 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 the inpatient study visit
• Subject is willing to avoid consumption of caffeine and caffeinated beverages for 24 hours prior to the inpatient study visit
• Subject is willing to avoid strenuous physical activity for 72 hours prior to the inpatient study visit
• Female subjects of child bearing potential must be willing to use acceptable birth control during study participation (oral contraceptives, intrauterine device, implanted or injectable contraceptives, abstinence).

You may not qualify if:

• 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:
• Liver disease or liver injury as indicated by abnormal liver function tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase , serum bilirubin) \>3 × upper limit of normal (ULN), or history of hepatic cirrhosis
• History or presence of impaired renal function as indicated by an estimated glomerular filtration rate \<60 ml/hr or urine albumin-to-creatinine ratio \>35 mg/mmol
• Significant cardiovascular disease, including Class III or greater congestive heart failure (CHF), coronary artery disease, second degree or greater heart block, or clinically significant arrhythmias; baseline second degree or greater heart block or prolonged QT syndrome (QTc interval ≥ 470 msec); or any major cardiovascular event within the last 3 years (including myocardial infarction, transient ischemic attack \[TIA\], cerebrovascular accident \[CVA\], angina, and hospitalization due to CHF, transient ischemic attack (TIA), and CVA)
• Metabolic, other or endocrine disorders, including diagnosis of type 1 or type 2 diabetes mellitus \[HbA1c ≥6.5%\]), inadequately treated hyperthyroidism (thyroid stimulating hormone \[TSH\] below normal range) or hypothyroidism (TSH above upper limit of normal if symptomatic or TSH \>10 U/mL), Cushing syndrome, Addison's disease, hypogonadism, or genetic disorders linked to obesity
• History of irritable bowel disease, recurrent nausea or vomiting
• Anemia (hemoglobin \<12 g/dl in men, \<11 g/dl in women)
• 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.

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead

Study Sites (1)

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (10)

• 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

• 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.

  PMID: 26434748 BACKGROUND

• Melzack R, Rosberger Z, Hollingsworth ML, Thirlwell M. New approaches to measuring nausea. CMAJ. 1985 Oct 15;133(8):755-8, 761.

  PMID: 4042058 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

• 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

Related Links

• Florida Hospital Translational Research Institute for Metabolism and Diabetes

MeSH Terms

Conditions

Obesity

Interventions

Glucagon

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Lauren Sparks, PhD

  Prinicipal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2016
• First Posted: June 29, 2016
• Study Start: November 1, 2016
• Primary Completion: January 13, 2017
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)