Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial

Margaret M. Band, Deepa Sumukadas, Allan D. Struthers, Alison Avenell, Peter T. Donnan, Paul R. Kemp, Karen T. Smith, Cheryl L. Hume, Adrian Hapca, Miles D. Witham (Lead / Corresponding author)

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Abstract

Background: Sarcopenia (the age related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot, or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exists from small studies for both interventions, but neither have yet been tested in adequately powered randomised trials in patients with sarcopenia.

Methods: Leucine and ACE inhibitors in sarcopenia (LACE) is a multi-centre, masked, placebo-controlled, 2x2 factorial randomised trial evaluating the efficacy of leucine and perindopril (ACEi) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on Bioimpedance Analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts, and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including micro RNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo.

Discussion: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia.
Original languageEnglish
Article number6
Pages (from-to)1-11
Number of pages11
JournalTrials
Volume19
DOIs
Publication statusPublished - 1 Jan 2018

Fingerprint

Sarcopenia
Clinical Protocols
Angiotensin-Converting Enzyme Inhibitors
Leucine
Randomized Controlled Trials
Perindopril
Therapeutics
Muscles
Placebos
Secondary Care
Resistance Training
Angiotensin Receptor Antagonists
Photon Absorptiometry
Muscle Strength
Peptidyl-Dipeptidase A
Genetic Polymorphisms
Activities of Daily Living
MicroRNAs
Genetic Markers
Cost-Benefit Analysis

Keywords

  • Leucine
  • Older people
  • Perindopril
  • Physical function
  • Quality of life
  • Randomised controlled trial
  • Sarcopenia

Cite this

Band, Margaret M. ; Sumukadas, Deepa ; Struthers, Allan D. ; Avenell, Alison ; Donnan, Peter T. ; Kemp, Paul R. ; Smith, Karen T. ; Hume, Cheryl L. ; Hapca, Adrian ; Witham, Miles D. / Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial) : study protocol for a randomised controlled trial. In: Trials. 2018 ; Vol. 19. pp. 1-11.
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abstract = "Background: Sarcopenia (the age related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot, or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exists from small studies for both interventions, but neither have yet been tested in adequately powered randomised trials in patients with sarcopenia.Methods: Leucine and ACE inhibitors in sarcopenia (LACE) is a multi-centre, masked, placebo-controlled, 2x2 factorial randomised trial evaluating the efficacy of leucine and perindopril (ACEi) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on Bioimpedance Analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts, and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including micro RNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. Discussion: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia.",
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Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial) : study protocol for a randomised controlled trial. / Band, Margaret M.; Sumukadas, Deepa; Struthers, Allan D.; Avenell, Alison; Donnan, Peter T.; Kemp, Paul R.; Smith, Karen T.; Hume, Cheryl L.; Hapca, Adrian; Witham, Miles D. (Lead / Corresponding author).

In: Trials, Vol. 19, 6, 01.01.2018, p. 1-11.

Research output: Contribution to journalArticle

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T1 - Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial)

T2 - study protocol for a randomised controlled trial

AU - Band, Margaret M.

AU - Sumukadas, Deepa

AU - Struthers, Allan D.

AU - Avenell, Alison

AU - Donnan, Peter T.

AU - Kemp, Paul R.

AU - Smith, Karen T.

AU - Hume, Cheryl L.

AU - Hapca, Adrian

AU - Witham, Miles D.

N1 - This project is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. Grant number: 13/53/03. The views expressed in this publication are those of the author(s) and not necessarily those of the MRC, NHS, NIHR or the Department of Health. The authors acknowledge the financial assistance and support of the NIHR Ageing Clinical Research Network and acknowledge support from the Chief Scientist Office, Scottish Government Support for Science funding stream. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Sarcopenia (the age related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot, or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exists from small studies for both interventions, but neither have yet been tested in adequately powered randomised trials in patients with sarcopenia.Methods: Leucine and ACE inhibitors in sarcopenia (LACE) is a multi-centre, masked, placebo-controlled, 2x2 factorial randomised trial evaluating the efficacy of leucine and perindopril (ACEi) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on Bioimpedance Analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts, and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including micro RNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. Discussion: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia.

AB - Background: Sarcopenia (the age related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot, or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exists from small studies for both interventions, but neither have yet been tested in adequately powered randomised trials in patients with sarcopenia.Methods: Leucine and ACE inhibitors in sarcopenia (LACE) is a multi-centre, masked, placebo-controlled, 2x2 factorial randomised trial evaluating the efficacy of leucine and perindopril (ACEi) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on Bioimpedance Analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts, and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including micro RNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. Discussion: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia.

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