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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by McGill University Health Center
Sponsor:
Information provided by (Responsible Party):
Jose Morais, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT01922167
First received: July 26, 2013
Last updated: November 18, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
Frail Elderly
Dietary Supplement: Leucine
Dietary Supplement: Alanine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Impact of Exercise Training and Leucine Supplementation in Frail Elderly Women With an Exploration Into Mechanistic Explanations

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Change from Baseline in Fractional Synthesis Rate (FSR) at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Physical Performance at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]

    Short Physical Performance Battery test, Timed-up-and-Go test 6 Minute Walk Test

    1 repetition maximum Hand-grip strength


  • Change from Baseline in Body Composition at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]
    Dual energy X-ray absorptiometry

  • Change from Baseline in Post-prandial responses at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]
    Will measure excursion curves of glucose, insulin, branched chain amino acids, and amino acid profile

  • Change from Baseline in Fasting levels at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]
    Will measure fasting levels of insulin growth factor-1 (IGF-1), interleukin-6 (IL-6), cortisol, as well as resting metabolic rate


Other Outcome Measures:
  • Change from Baseline in Quality of Life at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]
    EuroQuol EQ-5D-5L™

  • Change from Baseline in Mammalian target of rapamycin (mTOR) signalling proteins at 12 weeks [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]

    Quantity of the following proteins and their phosphorylation status:

    • Protein kinase B (Akt) and phosphorylation on Ser473
    • Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and phosphorylation on Thr37/46
    • Ribosomal protein S6 kinase beta-1 (S6K1) and phosphorylation on Thr389
    • Ribosomal protein S6 (rpS6) and phosphorylation on Ser240/244
    • Proline-rich Akt substrate of 40 kilodaltons (PRAS40) and phosphorylation on Thr246
    • Forkhead box O3a (FoxO3a) and phosphorylation on Thr32


Estimated Enrollment: 24
Study Start Date: November 2013
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Leucine
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
Placebo Comparator: Alanine
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

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01922167

Contacts
Contact: Connie Nardolillo 514-843-1665 connie.nardolillo@muhc.mcgill.ca

Locations
Canada, Quebec
Royal Victoria Hospital Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Connie Nardolillo    514-843-1665    connie.nardolillo@muhc.mcgill.ca   
Principal Investigator: José A Morais, MD         
Institut Universitaire de Gériatrie de Montréal Active, not recruiting
Montreal, Quebec, Canada, H3W 1W5
Sponsors and Collaborators
McGill University Health Center
Investigators
Principal Investigator: José A Morais, MD McGill University Health Center
  More Information

No publications provided

Responsible Party: Jose Morais, Associate Professor and Director, Division of Geriatric Medicine, McGill University; President of the Canadian Geriatrics Society, McGill University Health Center
ClinicalTrials.gov Identifier: NCT01922167     History of Changes
Other Study ID Numbers: MUHC-H-5461
Study First Received: July 26, 2013
Last Updated: November 18, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by McGill University Health Center:
Aging
Frailty
Leucine
Resistance Exercise

ClinicalTrials.gov processed this record on September 16, 2014