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

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

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.

Angiotensin converting enzyme inhibitor, Leucine, Randomized controlled trial, Sarcopenia
2190-5991
858-871
Achison, Marcus
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Adamson, Simon
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Akpan, Asangaedem
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Aspray, Terry
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Avenell, Alison
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Band, Margaret M
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Bashir, Tufail
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Burton, Louise A
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Cvoro, Vera
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Donnan, Peter T
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Duncan, Gordon W
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George, Jacob
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Gordon, Adam L
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Gregson, Celia L
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Hapca, Adrian
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Henderson, Emily
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Hume, Cheryl
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Jackson, Thomas A
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Kemp, Paul
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Kerr, Simon
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Kilgour, Alixe
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Lyell, Veronica
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Masud, Tahir
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McKenzie, Andrew
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McKenzie, Emma
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Patel, Harnish
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Pilvinyte, Kristina
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Roberts, Helen C
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Rossios, Christos
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Sayer, Avan A
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Smith, Karen T
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Soiza, Roy L
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Steves, Claire J
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Struthers, Allan D
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Sumukadas, Deepa
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Tiwari, Divya
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Whitney, Julie
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Witham, Miles D
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LACE study group
Achison, Marcus
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Adamson, Simon
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Akpan, Asangaedem
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Aspray, Terry
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Avenell, Alison
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Band, Margaret M
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Bashir, Tufail
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Burton, Louise A
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Cvoro, Vera
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Donnan, Peter T
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Duncan, Gordon W
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George, Jacob
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Gordon, Adam L
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Gregson, Celia L
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Hapca, Adrian
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Henderson, Emily
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Hume, Cheryl
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Jackson, Thomas A
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Kemp, Paul
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Kerr, Simon
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Kilgour, Alixe
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Lyell, Veronica
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Masud, Tahir
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McKenzie, Andrew
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McKenzie, Emma
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Patel, Harnish
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Pilvinyte, Kristina
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Roberts, Helen C
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Rossios, Christos
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Sayer, Avan A
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Smith, Karen T
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Soiza, Roy L
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Steves, Claire J
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Struthers, Allan D
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Sumukadas, Deepa
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Tiwari, Divya
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Whitney, Julie
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Witham, Miles D
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LACE study group (2022) Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial. Journal of Cachexia, Sarcopenia and Muscle, 13 (2), 858-871. (doi:10.1002/jcsm.12934).

Record type: Article

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.

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Accepted/In Press date: 17 January 2022
e-pub ahead of print date: 16 February 2022
Keywords: Angiotensin converting enzyme inhibitor, Leucine, Randomized controlled trial, Sarcopenia

Identifiers

Local EPrints ID: 455697
URI: http://eprints.soton.ac.uk/id/eprint/455697
ISSN: 2190-5991
PURE UUID: 6cfa3079-0e6c-4614-85fe-293899183785

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Date deposited: 30 Mar 2022 16:59
Last modified: 02 Sep 2022 18:14

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Contributors

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

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