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.

Potential application of anti-osteoporotic therapy to relieve sarcopenia in the elderly

“…In an observational study, patients with hypertension showed a slower rate of muscle strength loss with ACEI than with other hypertensive drugs 28 . However, a placebo-controlled, parallel-group, double-blind, randomized two-by-two analysis of causes showed no improvement in walking speed, muscle strength, or muscle mass after 12 months of perindopril in patients greater than or equal to 70 years of age with sarcopenia 29 . A randomized controlled study and meta-analysis showed the same results 30 , 31 .…”

Sarcopenia in the Cirrhotic Patient: Current Knowledge and Future Directions

“…J o u r n a l P r e -p r o o f 20 However, much more research is required because other research demonstrates minimal impact of RAAS inhibitors on indicators of muscle integrity [129,130,131] .…”

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

“…Participants aged 70 years and over with sarcopenia, according to the EWGSOP definition (2010) [5], were recruited between April 2016 and December 2019 to the LACE trial to investigate inhibition of sarcopenia using leucine and/or ACE inhibition as described (trial registration ISRCTN90094835) [31]. The trial was approved by the East of Scotland NHS research ethics committee (approval 14/ES/1099) and the UK Medicines and Healthcare Regulatory Authority (EudraCT number 2014-003455-61; Clinical Trial Authorisation number 36888/ 0001/001-0001); the trial was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.…”

“…The original study was a double-blind randomised controlled trial and sample preparation and analysis for this work was carried out without any access to information that could identify the individuals involved. The full trial protocol, inclusion and exclusion criteria as well as the main outcomes have been published [31,32]. Height, weight, and age were recorded, and overall muscle mass was initially estimated by bioimpedance to reduce the total number of DXA scans required as part of the screening process.…”