The Glucagonotropic Effect of Amino Acids in Humans

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Glucagonotropic Effect of Amino Acids in Humans

Conditions
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Healthy

Intervention / Treatment
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* Other: Amino acid bolus infusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: randomized, double-blinded, single-arm study. Participants act as their own controls.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Primary arm<br>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<br>* Equimolar bolus infusions of amino acids or saline (placebo)<br>|

What is the study measuring?
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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 |