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



Achison, Marcus, Adamson, Simon, Akpan, Asangaedem ORCID: 0000-0002-1764-8669, Aspray, Terry, Avenell, Alison, Band, Margaret M, Bashir, Tufail, Burton, Louise A, Cvoro, Vera, Donnan, Peter T
et al (show 28 more authors) (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). pp. 858-871.

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Abstract

<h4>Background</h4>This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia.<h4>Methods</h4>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.<h4>Results</h4>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)].<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: Angiotensin converting enzyme inhibitor, Leucine, Sarcopenia, Randomized controlled trial
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 04 Nov 2022 11:26
Last Modified: 18 Jan 2023 19:48
DOI: 10.1002/jcsm.12934
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165990