Clinical trial NCT05954923: The Glucagonotropic Effect of Amino Acids in Humans
Official title: The Glucagonotropic Effect of Amino Acids in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: The Novo Nordisk Foundation Center for Basic Metabolic Research
First posted: 2023-07-20
Enrollment: 12
Sex: MALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: randomized, double-blinded, single-arm study. Participants act as their own controls.
Primary purpose: BASIC_SCIENCE

Brief summary: The objective of the study is to delineate the glucagonotropic signal exerted by selected amino acids in human subjects as well as the metabolic clearance rate of these amino acids after intravenous infusion

Detailed description: After being informed about the study and the potential risks, each participant giving written informed consent will participate in six experimental days. The glucagonotropic effect and metabolic clearance of selected amino acids and saline (placebo), respectively, will be evaluated in 12 healthy individuals. After screening, each participant will undergo 6 double-blinded experimental days performed in randomized order. The experimental days will each last 75 minutes. The amino acids selected for the experiment are glutamine, arginine, alanine, leucine and proline.

Eligibility criteria: Inclusion Criteria:

* normal fasting plasma glucose and glycated hemoglobin (HbA1c) \< 42 mmol/mol
* body mass index (BMI) between 18.5 and 25 kg/m2
* Hemoglobin \> 8.3 mmol/L
* Age between 20 and 65 years
* oral and written informed consent

Exclusion Criteria:

* Diabetes
* first-degree relatives with diabetes
* fasting plasma triglycerides indicating dyslipidemia (\> 2 mmol/L)
* nephropathy (eGFR \< 60 ml/min) and/or microalbuminuria (albumine/creatinine ratio \> 30 microgram/mg)
* liver disease and/or ALT and/or AST levels \> 2 x upper normal reference limits.
* signs of liver fibrosis and/or steatosis evaluated by transient elastography (CAP \> 238 dB/min) and/or kPa \> 6.0) and/or FIB-4 index \> 1.45
* regular use of prescription medication
* use of dietary protein supplementation
* any condition the investigator feels would interfere with trial completion

Primary outcomes:
measure: bsAUC30
timeFrame: bsAUC is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min and 30 min
Secondary outcomes:
measure: AUC30
timeFrame: AUC30 is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min and 30 min
measure: AUC60
timeFrame: AUC60 is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min, 30 min and 60 min
measure: bsAUC60
timeFrame: bsAUC60 is calculated from blood samples drawn at times 0 min, 1 min, 2 min, 4 min, 6 min, 10 min, 15 min, 30 min and 60 min
measure: peak glucagon concentration
timeFrame: measured between time 0 min and time 60 min
Other outcomes:
measure: Metabolic clearance of amino acids
timeFrame: Time 0 min to time 60 min
measure: Insulin
timeFrame: Time -15 min to time 60 min
measure: C-peptide
timeFrame: Time -15 min to time 60 min
measure: Total and individual amino acids
timeFrame: Time -15 min to time 60 min
measure: GLP-1
timeFrame: Time -15 min to time 60 min
measure: GIP
timeFrame: Time -15 min to time 60 min
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research
Study officials:
References: