Effects of Glucagon Administration on Energy Expenditure (GLEE)

April 24, 2018 updated by: AdventHealth Translational Research Institute

A Prospective Randomized, Placebo (Saline)-Controlled, Balanced, 3-treatment Regimen Crossover Study Comparing the Effects of Prolonged (13 h) Hyperglucagonemia With Those of Acute (3 hr) Hyperglucagonemia on Energy Expenditure and Endogenous Glucose Protection (EGP).

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  1. To compare the effect of prolonged hyperglucagonemia to that of acute hyperglucagonemia on energy expenditure in healthy subjects using room indirect calorimetry in the setting of octreotide-mediated prevention of plasma insulin excursions.
  2. To compare the effects of prolonged hyperglucagonemia to acute hyperglucagonemia on EGP in healthy subjects in the setting of octreotide-mediated prevention of plasma insulin excursions.
  3. To determine the effects of prolonged hyperglucagonemia to acute hyperglucagonemia on rates of substrate oxidation, fibroblast growth factor21 and metabolites of interest.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Orlando, Florida, United States, 32804
        • Florida Hospital Translational Research Institute for Metabolism and Diabetes

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

  • consumes excessive amounts, defined as greater than 4 servings

    (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.

  • is currently a regular user (including "recreational use") of any illicit drugs or has a history of drug (including alcohol) abuse within approximately 3 months of the screening visit.
  • is unwilling or unable to adhere to the dietary needs during the study, or to consume the standardized meals during the study, and/or is on a carbohydrate restricted diet (i.e., a diet <100 grams per day of carbohydrate).
  • is any concern by the investigator regarding the safe participation of the subject in the trial or for any other reason; the investigator considers the subject inappropriate for participation in the trial.
  • has a history of claustrophobia or is claustrophobic.
  • has ever had an organ transplant.
  • is a smoker or uses other nicotine-containing products (for at least 6 months prior to drug administration); plans to begin smoking or using nicotine-containing products during the conduct of the study.
  • has poor intravenous access.
  • has used any medications that are known to influence glucose, fat, or energy metabolism within the last 3 months (growth hormones, steroids, etc.)
  • has blood pressure at screening visit less than or equal to 100/50 mm Hg or greater than or equal to 160/100 mm Hg.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Glucagon with Octreotide and insulin
Overnight (10 hours) infusion of glucagon, then 3 hours infusion of glucagon with concurrent infusions of Octreotide and insulin.
Drug: Octreotide
Other Names:
  • Sandostatin
Drug: Insulin
Other Names:
  • Hypoglycemic agent
Drug: Glucagon
Placebo Comparator: Placebo, Glucagon with Octreotide and Insulin
Overnight (10 hours) infusion of saline, then 3 hour infusion of glucagon with concurrent infusions of Octreotide and insulin.
Drug: Octreotide
Other Names:
  • Sandostatin
Drug: Insulin
Other Names:
  • Hypoglycemic agent
Drug: Glucagon
Behavioral: Placebo
Other Names:
  • Saline
Placebo Comparator: Placebo, with Octreotide and insulin
Overnight (10 hours) infusion of saline, then 3 hour infusion of saline with concurrent infusions of Octreotide and insulin.
Drug: Octreotide
Other Names:
  • Sandostatin
Drug: Insulin
Other Names:
  • Hypoglycemic agent
Behavioral: Placebo
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure of energy expenditure
Time Frame: Day 2, Day 9, Day 16
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measure of endogenous glucose production
Time Frame: Day 3, Day 10, Day 17
The measure of endogenous glucose production will be calculated from the deuterated glucose infusion rate and the plasma deuterated glucose enrichment using the non-steady state equation.
Day 3, Day 10, Day 17

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AdventHealth Translational Research Institute

Investigators

  • Principal Investigator: Christian Meyer, MD, Translational Research Institute for Metabolism and Diabetes

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (Actual)

June 1, 2015

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

September 4, 2014

First Submitted That Met QC Criteria

September 8, 2014

First Posted (Estimate)

September 11, 2014

Study Record Updates

Last Update Posted (Actual)

April 26, 2018

Last Update Submitted That Met QC Criteria

April 24, 2018

Last Verified

April 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TRIMDFH 601205

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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