Clinical trial NCT01735539: Dysfunction of Nutritive Blood Flow as a Determinant of Anabolic Resistance With Age; the Role of Amino Acids in Modulating Muscle Metabolism
Official title: Dysfunction of Nutritive Blood Flow as a Determinant of Anabolic Resistance in Older People; The Role of Essential Amino Acids in Modulating Muscle Protein Metabolism; Bolus vs. Pulse Feeding Strategies and the Ability of Arginine to Rejuvenate Microvascular Responsiveness.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Old Age (Focus; Not a Recognized Condition)
Keywords: old age
sarcopenia
essential amino acid
arginine
contrast enhanced ultrasound
muscle microcirculation
muscle protein synthesis
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2012-11-28
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators plan to measure changes in muscle protein metabolism in response to feeding, comparing between a single large essential amino acid (EAA) feed (the normal building blocks of protein) and the provision of the same dose in 4 smaller feeds at 45min intervals. The investigators will perform this study in healthy older (65-75y) and younger (18-28) men. The investigators will also explore how feeding affects muscle blood flow as this is important in the delivery of the nutrients we eat to the muscle where they are used.

The investigators plan to supplement the feed with arginine, a safe and widely found non-essential amino acid, to explore if this can improve muscle blood flow.

Detailed description: We will provide a 15g mixed essential amino acid feed or 4 x 3.75g.

There is sexual dimorphism thus initially we will just recruit males. Powering calculations dictate n=8 in each group.

We will use well established stable isotope tracer techniques (with 13C6 Phenylalanine) to measure muscle protein synthesis and breakdown by Gas Chromatography - combustion - isotope ratio mass spectroscopy.

We will measure leg blood flow by phase shift Doppler and muscle microvascular flow by contrast enhanced ultrasound.

Eligibility criteria: Inclusion Criteria:

* age 65-75 or 18-28

Exclusion Criteria:

* BMI \>30
* Diabetes
* Beta blocker or steroid use
* Established cerebrovascular, peripheral vascular or ischaemic heart disease.

Primary outcomes:
measure: Muscle Protein Synthesis (FSR, fractional synthetic rate, %/hr)
timeFrame: Across 6hr study
Secondary outcomes:
measure: Muscle Protein Breakdown (MPB)
timeFrame: Across 6hr study
measure: Whole leg blood flow
timeFrame: Across a 6hr study
measure: Muscle Microvascular Blood flow
timeFrame: Across a 6hr study
Other outcomes:
Locations:
city: Derby
country: United Kingdom
facility: University of Nottingham School of Graduate Entry Medicine and Health
Study officials:
affiliation: University of Nottingham
name: Philip J Atherton, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mitchell WK, Phillips BE, Williams JP, Rankin D, Lund JN, Smith K, Atherton PJ. A dose- rather than delivery profile-dependent mechanism regulates the "muscle-full" effect in response to oral essential amino acid intake in young men. J Nutr. 2015 Feb;145(2):207-14. doi: 10.3945/jn.114.199604. Epub 2014 Dec 10.