The Effect of Glucagon on Cerebral Glucose Metabolism in Healthy Humans (GluCoMet_CD)

This is a pilot study in which the investigators will investigate the effect of exogenous glucagon on cerebral glucose metabolism in healthy humans.

Participants will participate in either part C or part D of the study, and each participant will participate in three study days. During a study day the participant will receive an intravenous infusion of either glucagon, glucose (in an adjustable rate to match to glucose concentrations achieved with the glucagon infusion) or saline. During each study day an 18F-flouro-deoxy-glucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) scan will be performed to quantify cerebral glucose metabolism during the first part (acute effect) of the glucagon/glucose/saline infusion (part C) or the last part (later effect) of the glucagon/glucose/saline infusion (part D).

Study Overview

• Status: Active, not recruiting
• Conditions: Cerebral Glucose Metabolism
• Intervention / Treatment: Other: Glucagon (part C); Other: Saline (part C); Other: Glucagon (part D); Other: Saline (part D); Other: Glucose clamp (part C); Other: Glucose clamp (part D)

Detailed Description

Participants in this study will participate in four visits; one screening visit and three study days.

Participants will be instructed to avoid strenuous exercise and alcohol intake two days prior to each experimental visit. Participants will arrive at the Department of Clinical Physiology and Nuclear Medicine after an overnight (>10 hours) fast (including coffee and medicine).

On all three study days, two peripheral venous catheters will be placed in the antecubital vein of each arm (one for the collection of blood samples and one for infusions). After two initial blood samples the infusion of either saline, glucagon or glucose will be started. The infusion rate of glucagon will be 10 ng/kg/min. The infusion rate of glucose will be adjustable, and adjusted to match the blood glucose levels achieved on the glucagon study day.

During the infusion of saline, glucagon or glucose a 18F-FDG PET/CT scan will be performed. The 18F-FDG PET/CT scan will be performed either in the beginning of the infusions (approximately 15-55 min after the start of infusion) (for participants in part C) or in the end of the infusions (approximately 150-190 min after the start of infusion) (for participants in part D).

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 55 to 70 years
• BMI under or equal to 30 kg/m2
• Capable of understanding the participant information and signing the consent form

Exclusion Criteria:

• Enrolment in other research projects that might interfere with the study
• Diabetes diagnosis (type 1 and 2)
• Use of medications which, in the opinion of the investigator, may jeopardise participant's safety or compliance with the protocol
• Diagnosis of psychiatric disorders, dementias, or any other neurological disorders that in the opinion of the investigator precludes compliance with the study protocol, evaluation of the results or represents an unacceptable risk for the participants safety
• Severe claustrophobia
• Impaired liver og kidney function

• Cardiac problems including any of the following:

  1. Classified as being in New York Heart Association (NYHA) class III or IV
  2. Angina pectoris (chest pain) within the last 6 months
  3. Acute myocardial infarction (heart attack) within last 2 years
• Inadequately treated blood pressure at screening defined as repeated resting blood pressure outside the range 90-150 mmHg for systolic and 50-100 mmHg for diastolic.
• Active or recent malignant disease
• Current or history of severe alcohol use or drug/chemical abuse as per investigator's judgement
• Any chronic disorders or severe diseases which, in the opinion of the investigator, might jeopardise participant's safety or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute effect (part C): Glucagon, Saline and Glucose Clamp; The arm includes three study days. Study day sequence: Glucagon, Saline and Glucose clamp. An 18F-FDG PET scan will be performed approximately 15-55 minutes after infusion start.	Other: Glucagon (part C); 90 minutes intravenous infusion with glucagon (infusion rate of 10 ng/kg/min).; Other: Saline (part C); 90 minutes intravenous infusion with isotonic NaCl.; Other: Glucose clamp (part C); 90 minutes intravenous infusion of 20 % weight/volume glucose (in an ajustable rate to match the glucose levels achieved during the glucagon infusion).
Experimental: Acute effect (part C): Saline, Glucagon and Glucose Clamp; The arm includes three study days. Study day sequence: Saline, Glucagon and Glucose clamp. An 18F-FDG PET scan will be performed approximately 15-55 minutes after infusion start.	Other: Glucagon (part C); 90 minutes intravenous infusion with glucagon (infusion rate of 10 ng/kg/min).; Other: Saline (part C); 90 minutes intravenous infusion with isotonic NaCl.; Other: Glucose clamp (part C); 90 minutes intravenous infusion of 20 % weight/volume glucose (in an ajustable rate to match the glucose levels achieved during the glucagon infusion).
Experimental: Acute effect (part C): Glucagon, Glucose Clamp and Saline; The arm includes three study days. Study day sequence: Glucagon, Glucose clamp and Saline. An 18F-FDG PET scan will be performed approximately 15-55 minutes after infusion start.	Other: Glucagon (part C); 90 minutes intravenous infusion with glucagon (infusion rate of 10 ng/kg/min).; Other: Saline (part C); 90 minutes intravenous infusion with isotonic NaCl.; Other: Glucose clamp (part C); 90 minutes intravenous infusion of 20 % weight/volume glucose (in an ajustable rate to match the glucose levels achieved during the glucagon infusion).
Experimental: Later effect (part D): Glucagon, Saline and Glucose Clamp; The arm includes three study days. Study day sequence: Glucagon, Saline and Glucose clamp. An 18F-FDG PET scan will be performed approximately 150-190 minutes after infusion start.	Other: Glucagon (part D); 210 minutes intravenous infusion with glucagon (infusion rate of 10 ng/kg/min).; Other: Saline (part D); 210 minutes intravenous infusion with isotonic NaCl.; Other: Glucose clamp (part D); 210 minutes intravenous infusion of 20 % weight/volume glucose (in an ajustable rate to match the glucose levels achieved during the glucagon infusion).
Experimental: Later effect (part D): Saline, Glucagon and Glucose Clamp; The arm includes three study days. Study day sequence: Saline, Glucagon and Glucose clamp. An 18F-FDG PET scan will be performed approximately 150-190 minutes after infusion start.	Other: Glucagon (part D); 210 minutes intravenous infusion with glucagon (infusion rate of 10 ng/kg/min).; Other: Saline (part D); 210 minutes intravenous infusion with isotonic NaCl.; Other: Glucose clamp (part D); 210 minutes intravenous infusion of 20 % weight/volume glucose (in an ajustable rate to match the glucose levels achieved during the glucagon infusion).
Experimental: Later effect (part D): Glucagon, Glucose Clamp and Saline; The arm includes three study days. Study day sequence: Glucagon, Glucose clamp and Saline. An 18F-FDG PET scan will be performed approximately 150-190 minutes after infusion start.	Other: Glucagon (part D); 210 minutes intravenous infusion with glucagon (infusion rate of 10 ng/kg/min).; Other: Saline (part D); 210 minutes intravenous infusion with isotonic NaCl.; Other: Glucose clamp (part D); 210 minutes intravenous infusion of 20 % weight/volume glucose (in an ajustable rate to match the glucose levels achieved during the glucagon infusion).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral metabolic rate of glucose (CMRglc), acute effect (part C)	CMRglc is calculated based on the 18F-FDG PET/CT scan.	15-55 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral metabolic rate of glucose (CMRglc), later effect (part D)	CMRglc is calculated based on the 18F-FDG PET/CT scan.	150-190 minutes
Blood-brain glucose transfer capacity (Tmax), acute effect (part C)	Tmax is calculated based on the 18F-FDG PET/CT scan.	15-55 minutes
Blood-brain glucose transfer capacity (Tmax), later effect (part D)	Tmax is calculated based on the 18F-FDG PET/CT scan.	150-190 minutes
FDG net clearance (Ki), acute effect (part C)	Ki is calculated based on the 18F-FDG PET/CT scan.	15-55 minutes
FDG net clearance (Ki), later effect (part D)	Ki is calculated based on the 18F-FDG PET/CT scan.	150-190 minutes

Collaborators and Investigators

• Sponsor: Nicolai Jacob Wewer Albrechtsen
• Collaborators: University Hospital Bispebjerg and Frederiksberg
• Investigators: Principal Investigator: Nicolai J Wewer Albrecthsen, MD PhD, Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Study Chair: Lisbeth J Marner, MD PhD, University Hospital Bispebjerg and Frederiksberg

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 10, 2025
• First Posted (Actual): March 14, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Glucagon; Quantitative PET; 18F-FDG PET; Cerebral Glucose Metabolism; Blood-brain Glucose Transfer
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Inorganic Chemicals; Chlorine Compounds; Chemistry Techniques, Analytical; Pancreatic Hormones; Sodium Compounds; Blood Chemical Analysis; Clinical Chemistry Tests; Proglucagon; Chlorides; Hydrochloric Acid; Glucagon; Sodium Chloride; Glucose Clamp Technique
• Other Study ID Numbers: GluCoMet_pilotCD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No