This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia.
Placebo-controlled, parallel group, double-blind, randomised two-by-two factorial trial. We recruited adults aged ≥70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4m walk) and/or low handgrip strength (women <20kg, men <30kg) plus low muscle mass (using sex and BMI categoryspecific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomised to perindopril 4mg or placebo, and to oral leucine powder 2.5g 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.
We screened 320 people and randomised 145 participants compared to 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]) vs 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 -0.4kg [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]) vs 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 -0.3kg [95%CI -1.0 to 0.4], p=0.47). Meta-analysis of ACEi / 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]).
Neither perindopril nor leucine improved physical performance or muscle mass in this trial; metaanalysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.
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 ants to the trial, all the participants, and all the staff of the Tayside Clinical Trials Unit for their support of the trial.
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.
Data Availability StatementOnline supplementary material
Additional supporting information may be found online in the Supporting Information section at the end of the article
- Angiotensin converting enzyme inhibitor
- Randomised Controlled Tria
- Meta-Analysis as Topic
- Treatment Outcome
- Perindopril/therapeutic use
- Sarcopenia/drug therapy
- Hand Strength/physiology
- Physical Functional Performance
- Leucine/therapeutic use
- BIOELECTRICAL-IMPEDANCE ANALYSIS
- SKELETAL-MUSCLE MASS
- LOWER-EXTREMITY FUNCTION
- Randomized controlled trial