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CompletedNCT06685146Updated Apr 29, 2026

The Glucose-Independent Effects of Exogenous Glucagon on Insulin Secretion and Cognitive Function in Healthy Subjects

An interventional study of Glucagon Infusion and Glucose clamp in Glucose Metabolism and Insulin Secretion, sponsored by Nicolai Jacob Wewer Albrechtsen. Completed at 1 site in Denmark. Open to participants aged 25 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-04-29.

Sponsored by Nicolai Jacob Wewer Albrechtsen · Not applicable, Interventional, and Basic science

Phase
Not applicable
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
25 Years to 70 Years
Sex
All
01

Study summary

In this study the investigators will investigate the glucose-independent effects of exogenous glucagon on insulin secretion and cognitive function in healthy subjects.

Subjects will participate in two study days. The first study day is with a 240-minute infusion of glucagon and the second study day is with an infusion of glucose (clamped to match the glucose levels measured during the glucagon infusion). During the study day, blood samples will be drawn frequently and cognitive testing will be performed.

The investigators will investigate glucagon's glucose-independent effects on insulin secretion and cognitive function by comparing plasma measures of C-peptide and cognitive test scores between the glucagon study day and the glucose clamp study day.

Read the detailed description

Five-ten subjects with normal health will be included, and each subject will participate in two study days.

Participants will arrive after an overnight fast and will be placed in a hospital bed in a semi-recumbent position. In each antecubital vein an intravenous catheter will be placed; one for administration of glucagon or glucose and one for blood sampling. The first study day will be the glucagon study day. The blood measurements of glucose from the glucagon study day will be used for clamping the glucose levels during the glucose clamp study day.

Baseline blood samples will be drawn. At time 0 minutes the infusion of glucagon or glucose will be initiated. Glucagon will be infused at a rate of 10ng/kg/min. Blood glucose will be measured every five minutes for the first approximately 2.5 hours, and thereafter every 10-15 minutes. During the glucose-clamp study day the infusion rate of glucose will be adjusted continuously to match the glucose levels measured on the glucagon study day.

Blood samples for the analysis of plasma glucagon, insulin, C-peptide etc. will be drawn every five minutes for the first 60 minutes, and thereafter every 15-30 minutes.

After approximately three hours cognitive testing will be performed. After four hours, the infusion of either glucagon or glucose will be terminated. The final blood samples will be drawn 15 and 30 minutes after termination of the infusion.

02

Conditions studied

  • Glucose Metabolism
  • Insulin Secretion

Keywords

  • Glucagon
  • Glucose Metabolism
  • Cognition
  • Glucose clamp
  • Insulin secretion
  • C-peptide
03

In context

Lead sponsor

Nicolai Jacob Wewer Albrechtsen is the lead sponsor of 7 studies on the registry; 2 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
25 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Capable of understanding the participant information and signing the consent form
  • Between 25 and 70 years of age at the time of screening
  • Body mass index (BMI) ≤ 25 kg/m2 at the time of screening
  • A minimum of 7 years of schooling

Exclusion criteria

Exclusion Criteria:

  • Enrolment in other research projects that might interfere with the study
  • Diabetes diagnosis (type 1 and 2)
  • Pregnancy or breastfeeding
  • 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 function defined as either alanine aminotransferase (ALAT) and/or aspartate aminotransferase (ASAT) ≥ 2 times normal values
  • Kidney disease defined as serum creatinine levels ≥ 126 μmol/L for male and ≥ 111 μmol/L for female
  • 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
  • Inability to perform neuropsychological tests judged by the investigator (e.g. visual or auditory impairment or language barriers)
  • 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
05

Study design

Phase
Not applicable
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • Experimental
    Glucagon infusion followed by glucose-clamp

    The first study day is a 240 minutes infusion of glucagon (10ng/kg/min). The second study day is a 240 minutes infusion of glucose (20% w/v). The infusion rate of glucose will be adjusted continuously to match the levels of glucose measured on the glucagon study day.

    Other: Glucagon Infusion · Other: Glucose clamp

Interventions

  • OtherGlucagon Infusion

    A 240 minutes infusion of glucagon (10 ng/kg/min)

  • OtherGlucose clamp

    A 240 minutes infusion of 20 % w/v glucose. The infusion rate of glucose will be adjusted continuously to match the levels of glucose measured on the glucagon study day.

06

What researchers measure

Primary outcomes

  1. C-peptide (0-90 minutes)

    Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-90 minutes)

Secondary outcomes

  1. C-peptide to glucose ratio (0-90 minutes)

    Difference in plasma concentration of C-peptide assessed as area under the curve divided by plasma concentration of glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-90 minutes)

  2. C-peptide to glucose ratio (0-240 minutes)

    Difference in plasma concentration of C-peptide assessed as area under the curve divided by plasma concentration of glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  3. C-peptide (0-240 minutes)

    Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  4. C-peptide (0 minutes-glucose peak)

    Difference in plasma concentrations of C-peptide assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-time to plasma glucose peak concentration (assessed up to two hours))

  5. C-peptide deconvolution (0-240 minutes)

    Difference in deconvolution of plasma concentrations of C-peptide between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  6. Insulin (0-90 minutes)

    Difference in plasma concentrations of insulin assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-90 minutes)

  7. Insulin (0-240 minutes)

    Difference in plasma concentrations of insulin assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  8. Time to glucagon peak

    Time to glucagon peak on the glucagon study day

    Time frame: During intervention (0-240 minutes)

  9. Time to glucagon steady state

    Time to glucagon steady state on the glucagon study day

    Time frame: During intervention (0-240 minutes)

  10. Glucagon concentration at steady state

    Plasma glucagon steady state concentration on the glucagon infusion study day

    Time frame: During intervention (0-240 minutes)

  11. Glucose (0-90 minutes)

    Difference in plasma glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-90 minutes)

  12. Glucose (0-240 minutes)

    Difference in plasma glucose assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  13. Glucose peak

    Difference in plasma glucose peak concentration between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  14. Time to glucose peak

    Difference in time to plasma glucose peak concentration between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-time to plasma glucose peak concentration (assessed up to two hours)

  15. Glucose infused

    Glucose (g) infused on the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  16. cAMP (0-90 minutes)

    Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-90 minutes)

  17. cAMP (0-240 minutes)

    Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

  18. cAMP (240-300 minutes)

    Difference in plasma concentration of cAMP assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (240-300 minutes)

  19. Cognitive function

    Difference in cognitive function assessed as a composite score from the cognitive testing (SCIP testing) between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (180-240 minutes)

Other outcomes

  1. Word recall cognitive test

    Difference in the word recall cognitive test between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (180-240 minutes)

  2. Three-letter recall cognitive test

    Difference in the three-letter recall cognitive test between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (180-240 minutes)

  3. Verbal fluency cognitive test

    Difference in the verbal fluency cognitive test between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (180-240 minutes)

  4. Delayed word recall cognitive test

    Difference in the delayed word recall cognitive test between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (180-240 minutes)

  5. Visuomotor cognitive test

    Difference in the visuomotor cognitive test between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (180-240 minutes)

  6. Triglycerides (0-240 minutes)

    Difference in plasma concentration of triglycerides assessed as area under the curve between the glucagon infusion study day and the glucose clamp study day

    Time frame: During intervention (0-240 minutes)

07

Study locations

1 site
  • Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
    Copenhagen, 2400, Denmark
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 29, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06685146
Lead sponsor
Nicolai Jacob Wewer Albrechtsen
Responsible party
Nicolai Jacob Wewer Albrechtsen (Principal Investigator, University of Copenhagen) — Sponsor-investigator
First posted
Nov 12, 2024
Start date
Nov 8, 2024
Primary completion
Jul 21, 2025
Completion
Jul 21, 2025
Last update
Apr 29, 2026

Study contacts

Nicolai J Wewer Albrecthsen, MD PhD
principal investigator · Department of Clinical Biochemistry, Copenhagen University Hospital - Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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