The Glucagonotropic Effect of Amino Acids in Humans (STAMINA)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Amino acid bolus 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.

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

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Center for Clinical Metabolic Research

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary arm; This is a single-arm study. Each subject will participate in 6 experimental days in a randomized order. The interventions are equimolar bolus infusions of A) glutamine, B) arginine, C) alanine, D) leucine, E) proline and F) saline (placebo)	Other: Amino acid bolus infusion; Equimolar bolus infusions of amino acids or saline (placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bsAUC30	Baseline subtracted area under the curve for glucagon concentration during the first 30 minutes of the experiment	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC30	total area under the curve for glucagon concentration during the first 30 minutes of the experiment	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
AUC60	total area under the curve for glucagon concentration the first 60 minutes of the experiment	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
bsAUC60	Baseline subtracted area under the curve for glucagon concentration during the first 60 minutes of the experiment	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
peak glucagon concentration	the highest concentration of glucagon after infusion of amino acids/placebo	measured between time 0 min and time 60 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic clearance of amino acids	The metabolic clearance of each infused amino acid calculated from amino acid concentrations	Time 0 min to time 60 min
Insulin	plasma concentration of insulin during the experiment	Time -15 min to time 60 min
C-peptide	plasma concentration of C-peptide during the experiment	Time -15 min to time 60 min
Total and individual amino acids	plasma concentration of total and individual amino acids during the experiment	Time -15 min to time 60 min
GLP-1	plasma concentration of glucagon-like peptide 1 (GLP-1) during the experiment	Time -15 min to time 60 min
GIP	plasma concentration of glucose-dependent insulinotropic polypeptide (GIP) during the experiment	Time -15 min to time 60 min

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: The Novo Nordisk Foundation Center for Basic Metabolic Research

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2023
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 12, 2023
• First Posted (Actual): July 20, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: STAMINA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All published data will be made available to other researchers upon reasonable request

Drug and device information, study documents

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