Resistance Exercise Training and Amino Acid Leucine Supplementation in Frail Elderly Women

NCT01922167 | Completed

• 1 other identifier: MUHC-H-5461
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

Frailty is a clinical entity associated with an increase in risk for disease and death and becomes more common as people age. Frailty has a strong relationship with the age-related loss of muscle and strength, termed sarcopenia. Sarcopenia and frailty are strongly associated with disability, especially in women. Adequate protein intake, the amino acid leucine, and resistance exercise training have been individually shown to increase muscle mass to varying degrees. However, no studies have investigated how a longer-term resistance exercise training program with leucine supplementation when protein intake is optimized could increase muscle mass in frail and pre-frail elderly women. In addition, this is the population that stands the most to gain from such an intervention. The purpose of this study is to investigate the effects of the amino acid leucine added to resistance exercise training on muscle mass and physical performance in frail and pre-frail elderly women with adequate protein intake. We hypothesize that combining leucine in diet with an exercise program would be superior to exercise alone in stimulating muscle protein synthesis and phosphorylation status of muscle cellular key-regulatory proteins, leading to enhanced gains in muscle performance. A total of 24 subjects will take part in this study, conducted at the McGill University Health Centre (MUHC) Royal Victoria Hospital and the Institut Universitaire de Gériatrie de Montréal (IUGM). All subjects will undergo adjustments to their diet to optimize protein intake and a resistance exercise training program. Half of the participants will receive a supplement of powdered leucine (an amino acid), and the other half of the participants will receive a placebo in the same powder form. Neither the participants nor the study investigators will know which participants are receiving the leucine nor which are receiving the placebo. Each subjects participation in this study will involve 4 total visits: 2 initial screening visits followed by 2 two-day stays at the Centre for Innovative Medicine (CIM) of the MUHC-Royal Victoria Hospital. These two stays will be spaced by 12 weeks of the intervention (dietary adjustments, resistance exercise training, and the powdered supplement). The two stays each consist of a meal test to assess each subjects metabolic responses to a meal, and to obtain muscle biopsies necessary to measure the rate of protein accumulation in the muscle. Simple physical performance measurements will be taken before and at the completion of the intervention. This study aims to better understand how the presence of aging affects the body's responses to resistance exercise and how leucine, one of the amino acids that make up proteins, may help build muscle. This in turn, could lead to defining combined diet and exercise strategies to prevent muscle loss often seen with aging.

Conditions

Frail Elderly

Keywords

Aging; Frailty; Leucine; Resistance Exercise

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Fractional Synthesis Rate (FSR) at 12 weeks

  Baseline and at 12 weeks

Secondary Outcomes (4)

• Change from Baseline in Physical Performance at 12 weeks

  Baseline and at 12 weeks

• Change from Baseline in Body Composition at 12 weeks

  Baseline and at 12 weeks

• Change from Baseline in Post-prandial responses at 12 weeks

  Baseline and at 12 weeks

• Change from Baseline in Fasting levels at 12 weeks

  Baseline and at 12 weeks

Other Outcomes (2)

• Change from Baseline in Quality of Life at 12 weeks

  Baseline and at 12 weeks

• Change from Baseline in Mammalian target of rapamycin (mTOR) signalling proteins at 12 weeks

  Baseline and at 12 weeks

Study Arms (2)

Leucine

EXPERIMENTAL

2.5 g doses of leucine isolate three times per day (7.5 g total) of leucine, taken by mouth in powder form mixed with liquid for 12 consecutive weeks.

Dietary Supplement: Leucine

Alanine

PLACEBO COMPARATOR

2.5 g doses of alanine isolate three times per day (7.5 g total) of alanine, taken by mouth in powder form mixed with liquid for 12 consecutive weeks.

Dietary Supplement: Alanine

Interventions

Leucine DIETARY_SUPPLEMENT

Leucine

Alanine DIETARY_SUPPLEMENT

Alanine

Eligibility Criteria

• Age: 65 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Mini Mental State Examination score \> 24
• Time up and go test \< 17 s
• Stable weight and diet
• No acute disease
• Body mass index (BMI) 20-35 kg/m\^2
• Normal complete blood count (CBC), biochemistry, glycated hemoglobin (A1C), lipid profile, thyroid stimulating hormone (TSH)
• Non-diabetic (Oral Glucose Tolerance Test)
• Negative serology for hepatitis and human immunodeficiency virus (HIV)
• Normal chest X-Ray, electrocardiogram (ECG) and urine analysis
• Non-disabled
• Provide informed consent

You may not qualify if:

• Eating disorder,
• Food allergies affecting diet
• Substance abuse
• Active medical conditions including diabetes and any cancer other than skin within 5 years
• Serum creatinine \> 110 umol/L, Hb \< 110 g/L
• Medications known to interfere with the metabolic endpoint measurements: diuretics, beta-blockers, bronchodilators, non-steroidal anti-inflammatory drugs (NSAIDs), antianginals, antiarrythmics and steroids (other than topical)
• Disability

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Study Sites (2)

Institut Universitaire de Gériatrie de Montréal

Montreal, Quebec, H3W 1W5, Canada

Location

Royal Victoria Hospital - Glen Site

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (2)

• Jacob KJ, Sonjak V, Spendiff S, Hepple RT, Chevalier S, Perez A, Morais JA. Mitochondrial Content, but Not Function, Is Altered With a Multimodal Resistance Training Protocol and Adequate Protein Intake in Leucine-Supplemented Pre/Frail Women. Front Nutr. 2021 Jan 22;7:619216. doi: 10.3389/fnut.2020.619216. eCollection 2020.

  PMID: 33553232 DERIVED

• Jacob KJ, Chevalier S, Lamarche M, Morais JA. Leucine Supplementation Does Not Alter Insulin Sensitivity in Prefrail and Frail Older Women following a Resistance Training Protocol. J Nutr. 2019 Jun 1;149(6):959-967. doi: 10.1093/jn/nxz038.

  PMID: 31149709 DERIVED

MeSH Terms

Conditions

Frailty

Interventions

Leucine; Alanine

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• José A Morais, MD

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and Director, Division of Geriatric Medicine, McGill University; President of the Canadian Geriatrics Society

Study Record Dates

• First Submitted: July 26, 2013
• First Posted: August 14, 2013
• Study Start: November 1, 2013
• Primary Completion: February 8, 2018
• Study Completion: December 17, 2018
• Last Updated: March 8, 2019

Record last verified: 2019-03

Locations

CA (2)