Modulation of Muscle Protein Metabolism by Essential Amino Acids (Aj1B)

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.

Study Overview

• Status: Unknown
• Conditions: Old Age
• Intervention / Treatment: Dietary supplement: 15g Mixed Essential Amino Acids; Dietary supplement: 3g Leucine; Dietary supplement: 15g Mixed Essential Amino Acid REFEED

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Derby, United Kingdom, DE22 3DT
    • Recruiting
    • School of Graduate Entry Medicine
    • Contact: William K Mitchell, MA,MB,BChir; Phone Number: (+44)1332 724681; Email: kylemitchell@doctors.net.uk
    • Sub-Investigator: William K Mitchell, MA MB BChir
    • Principal Investigator: Philip J Atherton, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 75 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Ajinomoto Co., Inc.
• Investigators: Principal Investigator: Philip J Atherton, PhD, University of Nottingham

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): July 1, 2014

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 28, 2013
• First Posted (Estimate): July 1, 2013

Study Record Updates

• Last Update Posted (Estimate): January 17, 2014
• Last Update Submitted That Met QC Criteria: January 16, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Sarcopenia; Muscle; Old Age; Amino Acid
• Other Study ID Numbers: B13122012 GEM BMS