Clinical trial NCT06567665: Leucine Supplementation Strategies to Enhance Muscle Anabolic Responses in Older Age
Official title: Leucine Supplementation Strategies to Enhance Muscle Anabolic Responses in Older Age
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Muscle Protein Synthesis
Keywords: Aging
Muscle protein synthesis
Leucine
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2024-08-23
Enrollment: 10
Sex: MALE
Minimum age (years): 65
Maximum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Sarcopenia describes the progressive decline of muscle mass and strength with advancing age and is associated with increased frailty and morbidity, however we do not currently have an effective treatment. Protein feeding and exercise is known to increase muscle mass, but aged muscle shows a lower response to these stimuli leading to muscle loss over time. We do know that ingesting leucine, a building block of protein, can overcome this reduced response to protein feeding and exercise leading to increased muscle mass in older people. However, we do not understand when the optimum time to ingest leucine is to maximise muscle mass after exercise in older people. In this study we will examine the effect of feeding leucine after exercise either with a meal or between meals.


Eligibility criteria: Inclusion Criteria:

* Male, 65-75 years of age
* BMI 18-28 kg/m2
* Non smoker
* Not performing regular resistance type exercise
* Participant is willing and able to give informed consent for participation in the study

Exclusion Criteria:

* A BMI \<18 or \>28 kg·m-2
* Active cardiovascular disease: uncontrolled hypertension (BP \> 160/100), angina, heart failure (class III/IV), arrhythmia, right to left cardiac shunt or recent cardiac event
* Cerebrovascular disease: previous stroke, aneurysm (large vessel or intracranial)
* Respiratory disease including pulmonary hypertension or chronic obstructive pulmonary disease (COPD)
* Metabolic disease: hyper and hypo parathyroidism, untreated hyper and hypothyroidism, Cushing's disease, types 1 or 2 diabetes (treated and untreated), inborn/ congenital errors of metabolism (e.g. phenylketonuria (PKU), galactosaemia)
* Active inflammatory bowel disease
* Acute infection
* Acute or chronic renal disease
* Malignancy (or history of malignancy with 5 y)
* Recent steroid treatment (within 6 mo), or hormone replacement therapy
* Coagulopathy
* Musculoskeletal or neurological disorders
* Known allergies to any of the product ingredients
* Having taken part in a research study in the last 3 months involving invasive procedures or an inconvenience allowance

Primary outcomes:
measure: Muscle protein synthesis in response to leucine feeding
timeFrame: 7 days
Secondary outcomes:
measure: Measure muscle anabolic and catabolic signalling pathways in response to leucine feeding
timeFrame: 7 days
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: University of Nottingham
state: Nottinghamshire
Study officials:
affiliation: University of Nottingham
name: Matthew Brook, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol. 2012 Jul 11;3:260. doi: 10.3389/fphys.2012.00260. eCollection 2012.
citation: Atherton PJ, Smith K. Muscle protein synthesis in response to nutrition and exercise. J Physiol. 2012 Mar 1;590(5):1049-57. doi: 10.1113/jphysiol.2011.225003. Epub 2012 Jan 30.
citation: Wilkinson DJ, Bukhari SSI, Phillips BE, Limb MC, Cegielski J, Brook MS, Rankin D, Mitchell WK, Kobayashi H, Williams JP, Lund J, Greenhaff PL, Smith K, Atherton PJ. Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women. Clin Nutr. 2018 Dec;37(6 Pt A):2011-2021. doi: 10.1016/j.clnu.2017.09.008. Epub 2017 Sep 23.
citation: Katsanos CS, Kobayashi H, Sheffield-Moore M, Aarsland A, Wolfe RR. A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E381-7. doi: 10.1152/ajpendo.00488.2005. Epub 2006 Feb 28.
citation: Brook MS, Wilkinson DJ, Mitchell WK, Lund JN, Phillips BE, Szewczyk NJ, Greenhaff PL, Smith K, Atherton PJ. Synchronous deficits in cumulative muscle protein synthesis and ribosomal biogenesis underlie age-related anabolic resistance to exercise in humans. J Physiol. 2016 Dec 15;594(24):7399-7417. doi: 10.1113/JP272857. Epub 2016 Nov 7.