Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

LACE study group

doi:10.1002/jcsm.12934

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

LACE study group

Research output: Contribution to journal › Article › peer-review

23 Citations (Scopus)

Abstract

BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

Original language	English
Pages (from-to)	858-871
Number of pages	14
Journal	Journal of cachexia, sarcopenia and muscle
Volume	13
Issue number	2
DOIs	https://doi.org/10.1002/jcsm.12934
Publication status	Published - 1 Apr 2022

Keywords

Angiotensin converting enzyme inhibitor
Leucine
Randomized controlled trial
Sarcopenia

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10.1002/jcsm.12934

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@article{80a0c208b4094e00a56ccb1e7aee4043,

title = "Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial",

abstract = "BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.",

keywords = "Angiotensin converting enzyme inhibitor, Leucine, Randomized controlled trial, Sarcopenia",

author = "{LACE study group} and Marcus Achison and Simon Adamson and Asangaedem Akpan and Terry Aspray and Alison Avenell and Band, {Margaret M.} and Tufail Bashir and Burton, {Louise A.} and Vera Cvoro and Donnan, {Peter T.} and Duncan, {Gordon W.} and Jacob George and Gordon, {Adam L.} and Gregson, {Celia L.} and Adrian Hapca and Emily Henderson and Cheryl Hume and Jackson, {Thomas A.} and Paul Kemp and Simon Kerr and Alixe Kilgour and Veronica Lyell and Tahir Masud and Andrew McKenzie and Emma McKenzie and Harnish Patel and Kristina Pilvinyte and Roberts, {Helen C.} and Christos Rossios and Sayer, {Avan A.} and Smith, {Karen T.} and Soiza, {Roy L.} and Steves, {Claire J.} and Struthers, {Allan D.} and Deepa Sumukadas and Divya Tiwari and Julie Whitney and Witham, {Miles D.}",

note = "Funding Information: AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. The authors acknowledge support from the NIHR Ageing Clinical Research Network and the NHS Scotland Support for Science programme. The authors would also thank the efforts of all the research nurses and other site research staff who recruited participants to the trial, all the participants, and all the staff of the Tayside Clinical Trials Unit for their support of the trial. Funding Information: The LACE trial (project reference 13/53/03) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health and Social Care. Publisher Copyright: {\textcopyright} 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.",

year = "2022",

month = apr,

day = "1",

doi = "10.1002/jcsm.12934",

language = "English",

volume = "13",

pages = "858--871",

journal = "Journal of cachexia, sarcopenia and muscle",

issn = "2190-6009",

publisher = "Wiley Open Access",

number = "2",

}

TY - JOUR

T1 - Effect of perindopril or leucine on physical performance in older people with sarcopenia

T2 - the LACE randomized controlled trial

AU - LACE study group

AU - Achison, Marcus

AU - Adamson, Simon

AU - Akpan, Asangaedem

AU - Aspray, Terry

AU - Avenell, Alison

AU - Band, Margaret M.

AU - Bashir, Tufail

AU - Burton, Louise A.

AU - Cvoro, Vera

AU - Donnan, Peter T.

AU - Duncan, Gordon W.

AU - George, Jacob

AU - Gordon, Adam L.

AU - Gregson, Celia L.

AU - Hapca, Adrian

AU - Henderson, Emily

AU - Hume, Cheryl

AU - Jackson, Thomas A.

AU - Kemp, Paul

AU - Kerr, Simon

AU - Kilgour, Alixe

AU - Lyell, Veronica

AU - Masud, Tahir

AU - McKenzie, Andrew

AU - McKenzie, Emma

AU - Patel, Harnish

AU - Pilvinyte, Kristina

AU - Roberts, Helen C.

AU - Rossios, Christos

AU - Sayer, Avan A.

AU - Smith, Karen T.

AU - Soiza, Roy L.

AU - Steves, Claire J.

AU - Struthers, Allan D.

AU - Sumukadas, Deepa

AU - Tiwari, Divya

AU - Whitney, Julie

AU - Witham, Miles D.

N1 - Funding Information: AAS, TA, and MDW acknowledge support from the NIHR Newcastle Biomedical Research Centre. AA acknowledges support from the Health Services Research Unit, which is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate. The authors acknowledge support from the NIHR Ageing Clinical Research Network and the NHS Scotland Support for Science programme. The authors would also thank the efforts of all the research nurses and other site research staff who recruited participants to the trial, all the participants, and all the staff of the Tayside Clinical Trials Unit for their support of the trial. Funding Information: The LACE trial (project reference 13/53/03) is funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership. The views expressed in this publication are those of the authors and not necessarily those of the MRC, NIHR or the Department of Health and Social Care. Publisher Copyright: © 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

AB - BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

KW - Angiotensin converting enzyme inhibitor

KW - Leucine

KW - Randomized controlled trial

KW - Sarcopenia

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DO - 10.1002/jcsm.12934

M3 - Article

C2 - 35174663

AN - SCOPUS:85128160996

SN - 2190-6009

VL - 13

SP - 858

EP - 871

JO - Journal of cachexia, sarcopenia and muscle

JF - Journal of cachexia, sarcopenia and muscle

IS - 2

ER -

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

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