Effect of Prolonged (72 Hour) Glucagon Administration on Energy Expenditure in Healthy Obese Subjects

NCT03139305 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: TRIMDFH 954476
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to examine the effect of prolonged (72 hour) administration of glucagon compared to placebo on energy expenditure in healthy, non-diabetic, obese subjects.

Conditions

Obesity

Keywords

glucagon

Outcome Measures

Primary Outcomes (2)

• Energy Expenditure

  24 hours

• Effects of continuous IV infusion of glucagon versus placebo

  Overall well-being will be measured by administering a questionnaire with a scale from none to severe.

  72 hours

Study Arms (3)

Glucagon Low Dose

ACTIVE COMPARATOR

Drug: Glucagon

Glucagon High Dose

ACTIVE COMPARATOR

Drug: Glucagon

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Glucagon DRUG

Low dose intravenous infusion for 72 hours at 12.5 ng/kg/min

Glucagon Low Dose

Placebo DRUG

Intravenous infusion of saline for 72 hours

Placebo

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.
• Body Mass Index (BMI) ≥27 to ≤45 kg/m2 and body weight \<450 lbs.
• Stable body weight for 3 months (self-reported loss/gain \<5%).
• Judged to be non-diabetic per the American Diabetes Association guidelines:
• fasting plasma glucose \<126 mg/dL \[7.0 mmol/L\] and
• HbA1c \<6.5% \[48 mmol/mol\]) and
• in good health on the basis of medical history, physical examination (PE), electrocardiogram (ECG), and normal laboratory values obtained from Screening visit labs.
• 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.
• Willing to avoid alcohol consumption for 48 hours prior to the inpatient study visit.
• Willing to avoid consumption of caffeine and caffeinated beverages for 24 hours prior to the inpatient study visit.
• Willing to avoid strenuous physical activity for 72 hours prior to the inpatient study visit.

You may not qualify if:

• Treatment with any medication known to significantly impact body weight or energy metabolism (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).
• Treatment with a selective serotonin reuptake inhibitor, a medication for depression or apomorphine within one week prior to screening due to interaction with Zofran.
• History of bariatric surgery.
• Current liver, renal, pulmonary, cardiac, oncologic, metabolic, gastrointestinal, or hematologic disease which the Investigator believes is clinically significant, including:
• a. 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.
• Impaired renal function as indicated by an estimated glomerular filtration rate (eGFR) \<60 mL/min 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 \[MI\], transient ischemic attack, cerebrovascular accident \[CVA\], angina, and hospitalization due to CHF,transient ischemic attack, and CVA).
• Metabolic, or other 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 \>ULN \<10 U/mL and symptomatic or TSH \>10 U/mL), Cushing's disease/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 males, \<11 g/dL in females).
• History of dyslipidemia: Fasting triglycerides (TG) \>500 mg/dL and low-density lipoproteins (LDL) \>250 mg/dL.
• Self-reported history of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (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/BiPAP/AutoPAP.
• Major surgery within 3 months prior to screening.

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 (14)

• Arafat AM, Kaczmarek P, Skrzypski M, Pruszynska-Oszmalek E, Kolodziejski P, Szczepankiewicz D, Sassek M, Wojciechowicz T, Wiedenmann B, Pfeiffer AF, Nowak KW, Strowski MZ. Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis? Diabetologia. 2013 Mar;56(3):588-97. doi: 10.1007/s00125-012-2803-y. Epub 2012 Dec 22.

  PMID: 23262585 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.

  PMID: 19853906 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

• Cegla J, Troke RC, Jones B, Tharakan G, Kenkre J, McCullough KA, Lim CT, Parvizi N, Hussein M, Chambers ES, Minnion J, Cuenco J, Ghatei MA, Meeran K, Tan TM, Bloom SR. Coinfusion of low-dose GLP-1 and glucagon in man results in a reduction in food intake. Diabetes. 2014 Nov;63(11):3711-20. doi: 10.2337/db14-0242. Epub 2014 Jun 17.

  PMID: 24939425 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

• 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

• Kim J, Heshka S, Gallagher D, Kotler DP, Mayer L, Albu J, Shen W, Freda PU, Heymsfield SB. Intermuscular adipose tissue-free skeletal muscle mass: estimation by dual-energy X-ray absorptiometry in adults. J Appl Physiol (1985). 2004 Aug;97(2):655-60. doi: 10.1152/japplphysiol.00260.2004. Epub 2004 Apr 16.

  PMID: 15090482 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

• 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

• 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

• 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

• 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

• 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

• Whytock KL, Carnero EA, Vega RB, Tillner J, Bock C, Chivukula K, Yi F, Meyer C, Smith SR, Sparks LM. Prolonged Glucagon Infusion Does Not Affect Energy Expenditure in Individuals with Overweight/Obesity: A Randomized Trial. Obesity (Silver Spring). 2021 Jun;29(6):1003-1013. doi: 10.1002/oby.23141.

  PMID: 34029448 DERIVED

Related Links

• 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

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 10, 2017
• First Posted: May 3, 2017
• Study Start: October 24, 2017
• Primary Completion: February 14, 2018
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)