Can Supplemental Leucine Offset Disuse-induced Muscle Atrophy?

NCT03762278 | Completed DMC

• 1 other identifier: RG_16-206
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Ageing is associated with a gradual decline in muscle mass that is detrimental to both physical function and metabolic health, increasing the risk of morbidity and mortality. The loss of protein muscle mass with ageing is poorly understood, but it may partly relate to inactivity/disuse (i.e. during injury or hospitalization). Periods of inactivity/disuse blunt the ability of muscle to grow (termed anabolic blunting), leading to a loss of muscle mass and strength. An accumulation of these periods over a lifetime promotes the devastating loss of muscle protein mass and strength seen with ageing. Disuse-induced muscle loss is underpinned by a blunted muscle anabolic response to protein nutrition. Supplementing the diet with the amino acid leucine may offer a potential solution to alleviate muscle mass and strength loss during disuse. In fact, leucine is suggested to promote muscle protein growth and reduce muscle protein loss during disuse in rats, but this is yet to be shown in humans. Accordingly, the proposed study will investigate whether leucine supplementation can offset muscle and strength loss during short-term disuse. Twenty-four healthy (non-obese, non-diabetic, non-smokers) men aged 18-35 years will initially complete a lower-limb strength assessment and undergo a body composition scan three days later. The following morning, participants will be randomly assigned to ingest either 5g of leucine (n=12) or a caloric-matched placebo (n=12) with each meal over a 7 d period of a single-leg immobilisation. Immediately following immobilisation participants will undergo another body composition scan. Additionally, a stable isotope infusion will be combined with serial muscle biopsies from the thigh of each leg to determine the measure rates of muscle protein synthesis in the fasted state and in the 'early' and 'late' phase of feeding. A day later, the assessment of muscle strength will be repeated.

Conditions

Muscle Disuse Atrophy

Keywords

Unilateral Immobilisation; Leucine; Muscle Wasting; Nutritional Intervention

Outcome Measures

Primary Outcomes (1)

• The change in the lean mass of the leg muscles following the 7 day immobilisation period.

  The change in the lean mass of the leg muscles following the 7 day immobilisation period.

  At baseline and then 7-days following the onset of immobilisation

Secondary Outcomes (1)

• The rates of post-absorptive and post-prandial myofibrillar protein synthesis response to 20 g of milk protein after a 7 day period of disuse.

  After 7 days of single-leg immobilisation in both the immobilised and non-immobilised leg

Study Arms (4)

Immobilised leg and leucine

EXPERIMENTAL

Participants consuming leucine supplementation with measures obtained from the uni-laterally immobilised leg.

Dietary Supplement: Leucine

Non-immobilised leg and leucine

ACTIVE COMPARATOR

Participants consuming leucine supplementation with measures obtained from the non-immobilised leg.

Dietary Supplement: Leucine

Immobilised leg and placebo

PLACEBO COMPARATOR

Participants consuming placebo supplementation with measures obtained from the uni-laterally immobilised leg.

Dietary Supplement: Placebo

Non-immobilised leg and placebo

PLACEBO COMPARATOR

Participants consuming placebo supplementation with measures obtained from the non-immobilised leg.

Dietary Supplement: Placebo

Interventions

Leucine DIETARY_SUPPLEMENT

Participants will ingest 15g of leucine supplementation/day during the immobilisation period. Leucine supplementation will be administered in powdered form (Infinit Nutrition, Canada) and participants will be required to consume 5g of leucine mixed with 250-300 ml of water during each meal. Leucine is a dietary supplement according to the US FDA. This supplementation protocol has been demonstrated in humans (Murphy et al., 2016, AJCN) with no reported side effects. The quantity of leucine supplementation falls well within the safe limits outlined by Rasmussen et al. (2016). Infinit Nutrition Leucine is in compliance with banned substances requirements as espoused by the World Anti-Doping Agency. Infinit Nutrition Leucine is not a medicinal product.

Also known as: Infinit Nutrition Leucine

Immobilised leg and leucine; Non-immobilised leg and leucine

Placebo DIETARY_SUPPLEMENT

Participants will ingest 15g of placebo supplementation/day during the immobilisation period. Placebo supplementation will be administered in powdered form and participants will be required to consume 5g of placebo supplementation mixed with 250-300 ml of water during each meal (3x/day). Placebo supplementation will contain 5g of non-essential amino acids (Infinit Nutrition, Canada) and will be calorically matched to the leucine supplementation.This supplementation protocol has been demonstrated previously in humans, with no reported side effects (Murphy et al., 2016, AJCN).

Also known as: Infinit Nutrition Placebo

Immobilised leg and placebo; Non-immobilised leg and placebo

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Participants must be male.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age: 18-35 years old
• Sex: male
• BMI: 18-25 kg/m2
• Diagnosis and general health: Good general health defined as (i) no known cardiovascular or metabolic disease, ii) non-smokers, iii) accustomed to normal levels of physical activity
• Compliance: understands and is willing, able and likely to comply with all study procedures and restrictions.
• Consent: demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent

You may not qualify if:

• Health problems such as: i) heart disease, ii) rheumatoid arthritis, iii) diabetes, iv) poor lung function, v) uncontrolled hypertension, vi) lactose intolerance or viI) any health conditions that might put the participant at risk for this study.
• Family history of thrombosis
• Involvement in regular structured exercise (resistance or endurance) training at the time of the study.
• Regular consumption of any analgesic or anti-inflammatory drug(s), either prescription or non-prescription
• Taking any medications known to affect protein metabolism (e.g. b-blockers, corticosteroids, non-steroidal anti- inflammatories, or prescription strength acne medications). Additional medications and/or supplementation aids (e.g. whey protein) will be deemed inappropriate based on the PI's discretion.
• Daily protein intake; individuals with protein intake that equates to \<0.8 or \>1.2 g/kg/day will be excluded from the proposed study, as altering the daily protein intake of individuals drastically over the 7 day period is expected to significantly impact muscle protein metabolism independent of the supplementation and/or immobilisation protocol.
• Infused with a stable isotope within 3 years prior to study participation

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (1)

University of Birmingham, School of Sport, Exercise and Rehabilitation Sciences

Edgbaston, West Midlands, B15 2TT, United Kingdom

Location

Related Publications (1)

• Edwards SJ, Smeuninx B, Mckendry J, Nishimura Y, Luo D, Marshall RN, Perkins M, Ramsay J, Joanisse S, Philp A, Breen L. High-dose leucine supplementation does not prevent muscle atrophy or strength loss over 7 days of immobilization in healthy young males. Am J Clin Nutr. 2020 Nov 11;112(5):1368-1381. doi: 10.1093/ajcn/nqaa229.

  PMID: 32910813 DERIVED

MeSH Terms

Conditions

Muscular Disorders, Atrophic; Muscular Atrophy

Interventions

Leucine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential

Study Officials

• Leigh Breen, PhD

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2017
• First Posted: December 3, 2018
• Study Start: March 1, 2017
• Primary Completion: February 1, 2019
• Study Completion: May 1, 2019
• Last Updated: June 11, 2020

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)