Modulation of Muscle Protein Metabolism by Essential Amino Acids

Study Overview
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Brief Summary
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The investigators plan to explore the ability of amino acids, the building blocks of proteins in our bodies and in the food we eat, to stimulate muscles to grow and stay strong. The investigators will investigate how rapidly after one meal the human body is ready to make use of a second meal and look at the molecular mechanisms underlying this. The investigators will look at these phenomena in older men as this group is known to be subject to a gradual loss of muscle mass and strength.

Detailed Description
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Muscles can stay very constant in size for much of adult life yet dramatic wasting is seen in advanced age and ill health. A better understanding of how muscles regulate their size will help design treatments to slow wasting in disease and to promote active aging. We plan to study a group of older men,  70yrs, the age at which muscle bulk starts to decrease, to observe how the muscles respond to feeding. We will provide a drink that contains the digested products of proteins from which muscles are built. Taking blood samples and some tiny biopsies of muscle (done under local anaesthesia) will allow us to measure muscle turnover and we will be able to measure for how long after a meal muscles actively take in nutrients before becoming full. We will also measure how long the muscle remains full before it returns to a state where it can again be stimulated to take in nutrients. We will also explore if leucine, one of the component parts of protein (especially in meat and dairy products) and a food widely used supplement, can promote the early re-stimulation of muscle by eating.

Official Title
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Modulation of Muscle Protein Metabolism by Essential Amino Acids

Conditions
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Old Age

Intervention / Treatment
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* Dietary Supplement: 15g Mixed Essential Amino Acids
* Dietary Supplement: 3g Leucine
* Dietary Supplement: 15g Mixed Essential Amino Acid REFEED


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male 65-75yrs BMI 18-28 Exclusion Criteria: Type 2 Diabetes mellitus Neurological Disease Significant cardiac, hepatic or renal disease Active malignancy Medication inc. Corticosteroids, NSAID use, Beta adrenoblockers.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early leucine refeed<br>15g Mixed Essential Amino Acids. 90 min delay. 3g Leucine | Dietary Supplement: 15g Mixed Essential Amino Acids<br>* Dissolved in 250ml water.<br>Dietary Supplement: 3g Leucine<br>* Dissolved in 250ml water.<br>|
| Experimental: Early EAA refeed<br>15g Mixed Essential Amino Acids. 90 min delay. 15g Mixed Essential Amino Acid REFEED | Dietary Supplement: 15g Mixed Essential Amino Acids<br>* Dissolved in 250ml water.<br>Dietary Supplement: 15g Mixed Essential Amino Acid REFEED<br>* Dissolved in 250ml water.<br>|
| Experimental: Mid latency EAA refeed<br>15g Mixed Essential Amino Acids. 150 min delay. 15g Mixed Essential Amino Acid REFEED | Dietary Supplement: 15g Mixed Essential Amino Acids<br>* Dissolved in 250ml water.<br>Dietary Supplement: 15g Mixed Essential Amino Acid REFEED<br>* Dissolved in 250ml water.<br>|
| Experimental: Late latency EAA refeed<br>15g Mixed Essential Amino Acids. 210 min delay. 15g Mixed Essential Amino Acid REFEED | Dietary Supplement: 15g Mixed Essential Amino Acids<br>* Dissolved in 250ml water.<br>Dietary Supplement: 15g Mixed Essential Amino Acid REFEED<br>* Dissolved in 250ml water.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myofibrillar Fractional Synthetic Rate | Assessed by gas-chromatography-combustion-mass spectrometry, using incorporation of a stable isotope tracer (13-C-6 Phe) | 6-10hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Leg blood flow | Common femoral bulk flow (Doppler USS) | 6-10hrs | 
| mTORC1 and AKT phosphorylation | Western Immunoblotting | 6-10hrs | 
| Muscle Protein Breakdown | By Arteriovenous limb balance | 6-10hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscle, Old Age, Sarcopenia, Amino Acid