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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,...

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Autores principales: Achison, Marcus, Adamson, Simon, Akpan, Asangaedem, Aspray, Terry, Avenell, Alison, Band, Margaret M., Bashir, Tufail, Burton, Louise A., Cvoro, Vera, Donnan, Peter T., Duncan, Gordon W., George, Jacob, Gordon, Adam L., Gregson, Celia L., Hapca, Adrian, Henderson, Emily, Hume, Cheryl, Jackson, Thomas A., Kemp, Paul, Kerr, Simon, Kilgour, Alixe, Lyell, Veronica, Masud, Tahir, McKenzie, Andrew, McKenzie, Emma, Patel, Harnish, Pilvinyte, Kristina, Roberts, Helen C., Rossios, Christos, Sayer, Avan A., Smith, Karen T., Soiza, Roy L., Steves, Claire J., Struthers, Allan D., Sumukadas, Deepa, Tiwari, Divya, Whitney, Julie, Witham, Miles D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977979/
https://www.ncbi.nlm.nih.gov/pubmed/35174663
http://dx.doi.org/10.1002/jcsm.12934
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author Achison, Marcus
Adamson, Simon
Akpan, Asangaedem
Aspray, Terry
Avenell, Alison
Band, Margaret M.
Bashir, Tufail
Burton, Louise A.
Cvoro, Vera
Donnan, Peter T.
Duncan, Gordon W.
George, Jacob
Gordon, Adam L.
Gregson, Celia L.
Hapca, Adrian
Henderson, Emily
Hume, Cheryl
Jackson, Thomas A.
Kemp, Paul
Kerr, Simon
Kilgour, Alixe
Lyell, Veronica
Masud, Tahir
McKenzie, Andrew
McKenzie, Emma
Patel, Harnish
Pilvinyte, Kristina
Roberts, Helen C.
Rossios, Christos
Sayer, Avan A.
Smith, Karen T.
Soiza, Roy L.
Steves, Claire J.
Struthers, Allan D.
Sumukadas, Deepa
Tiwari, Divya
Whitney, Julie
Witham, Miles D.
author_facet Achison, Marcus
Adamson, Simon
Akpan, Asangaedem
Aspray, Terry
Avenell, Alison
Band, Margaret M.
Bashir, Tufail
Burton, Louise A.
Cvoro, Vera
Donnan, Peter T.
Duncan, Gordon W.
George, Jacob
Gordon, Adam L.
Gregson, Celia L.
Hapca, Adrian
Henderson, Emily
Hume, Cheryl
Jackson, Thomas A.
Kemp, Paul
Kerr, Simon
Kilgour, Alixe
Lyell, Veronica
Masud, Tahir
McKenzie, Andrew
McKenzie, Emma
Patel, Harnish
Pilvinyte, Kristina
Roberts, Helen C.
Rossios, Christos
Sayer, Avan A.
Smith, Karen T.
Soiza, Roy L.
Steves, Claire J.
Struthers, Allan D.
Sumukadas, Deepa
Tiwari, Divya
Whitney, Julie
Witham, Miles D.
collection PubMed
description 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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spelling pubmed-89779792022-04-05 Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial Achison, Marcus Adamson, Simon Akpan, Asangaedem Aspray, Terry Avenell, Alison Band, Margaret M. Bashir, Tufail Burton, Louise A. Cvoro, Vera Donnan, Peter T. Duncan, Gordon W. George, Jacob Gordon, Adam L. Gregson, Celia L. Hapca, Adrian Henderson, Emily Hume, Cheryl Jackson, Thomas A. Kemp, Paul Kerr, Simon Kilgour, Alixe Lyell, Veronica Masud, Tahir McKenzie, Andrew McKenzie, Emma Patel, Harnish Pilvinyte, Kristina Roberts, Helen C. Rossios, Christos Sayer, Avan A. Smith, Karen T. Soiza, Roy L. Steves, Claire J. Struthers, Allan D. Sumukadas, Deepa Tiwari, Divya Whitney, Julie Witham, Miles D. J Cachexia Sarcopenia Muscle Original Articles 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. John Wiley and Sons Inc. 2022-02-16 2022-04 /pmc/articles/PMC8977979/ /pubmed/35174663 http://dx.doi.org/10.1002/jcsm.12934 Text en © 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. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Achison, Marcus
Adamson, Simon
Akpan, Asangaedem
Aspray, Terry
Avenell, Alison
Band, Margaret M.
Bashir, Tufail
Burton, Louise A.
Cvoro, Vera
Donnan, Peter T.
Duncan, Gordon W.
George, Jacob
Gordon, Adam L.
Gregson, Celia L.
Hapca, Adrian
Henderson, Emily
Hume, Cheryl
Jackson, Thomas A.
Kemp, Paul
Kerr, Simon
Kilgour, Alixe
Lyell, Veronica
Masud, Tahir
McKenzie, Andrew
McKenzie, Emma
Patel, Harnish
Pilvinyte, Kristina
Roberts, Helen C.
Rossios, Christos
Sayer, Avan A.
Smith, Karen T.
Soiza, Roy L.
Steves, Claire J.
Struthers, Allan D.
Sumukadas, Deepa
Tiwari, Divya
Whitney, Julie
Witham, Miles D.
Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial
title Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial
title_full Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial
title_fullStr Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial
title_full_unstemmed Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial
title_short Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial
title_sort effect of perindopril or leucine on physical performance in older people with sarcopenia: the lace randomized controlled trial
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8977979/
https://www.ncbi.nlm.nih.gov/pubmed/35174663
http://dx.doi.org/10.1002/jcsm.12934
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