Local Effects of Amino Acids and 3-hydroxybutyrate in the Bilaterally Perfused Human Leg

Study Overview
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Brief Summary
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Introduction: Protein loss during critical illness is an important problem and is shown to predict overall survival. In animal studies, infusion of leucine is shown to increase the synthesis of muscle protein by 30-40% and decrease protein degradation by 30%. Objectives: Compared to saline, an amino acid or 3hydroxybutyrate infusion in the femoral artery will promote protein synthesis and inhibit breakdown assessed with local a/v phenylalanine and tyrosine tracer kinetics in healthy volunteers. These effects will include distinct alterations in muscle signal events, in particular mTOR. Methods: n = 10 healthy male subjects are equipped with catheters in aa. femorals and vv. femorals bilaterally under local anaesthetics. Each study comprises a 3-hour basal period and a 3-hour period with hyperinsulinaemic-euglycaemic clamp. During the test, samples of arterial and venous blood and 4 muscle biopsies are obtained. The intervention contain continues saline infusion compared to either amino acids (Vamin) or 3hydroxybutyrate solution FFa-3OHB. Perspectives: This study elucidates the direct effect of aminoacids and ketone bodies on muscle protein metabolism in humans and contribute to further development of nutritional therapy in human catabolic states.

Official Title
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Local Effects of Amino Acids and 3-hydroxybutyrate in the Bilaterally Perfused Human Leg

Conditions
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Critical Illness, Protein Metabolism, Pharmaconutrients

Intervention / Treatment
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* Dietary Supplement: Vamin (Fresenius Kabi)
* Dietary Supplement: 3hydroxybutyrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 19 and 28 Written consent before study start Exclusion Criteria: Diabetes Inclusion in other studies using ionizing radiation. Allergic to egg or soy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amino acids<br>Amino acids compared to saline | Dietary Supplement: Vamin (Fresenius Kabi)<br>* Vamin 18gN 1ml/min infusion in 6 hours<br>|
| Active Comparator: 3hydroxybutyrat (3OHB)<br>Ketone body, 3OHB compared to saline | Dietary Supplement: 3hydroxybutyrate<br>* Goldbio, FFA-3OHB, dry powder mixed with sterile water at Aarhus University hospital pharmacy.<br>* Other names: 3OHB, 3hydroxybutyric acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in muscle metabolism after administration of amino acids. | Measured by arterio-venous differences of isotope tracers | Basal period and a glucose clamp (6 hours pr.day) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracellular mTOR and pAkt signal activation after infusion of amino acids. | 4 muscle biopsies measured for mTOR and pAkt activation by western blotting | Basal period and a glucose clamp (6 hours pr. day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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critical illness, protein metabolism, pharmaconutrients