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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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, 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.
Results
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]).
Conclusions
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.
Original languageEnglish
Pages (from-to)858-871
Number of pages14
JournalJournal of Cachexia, Sarcopenia and Muscle
Volume13
Issue number2
Early online date16 Feb 2022
DOIs
Publication statusPublished - 1 Apr 2022

Keywords

  • Angiotensin converting enzyme inhibitor
  • Leucine
  • Sarcopenia
  • Randomised Controlled Tria
  • Meta-Analysis as Topic
  • Humans
  • Male
  • Treatment Outcome
  • Perindopril/therapeutic use
  • Sarcopenia/drug therapy
  • Hand Strength/physiology
  • Female
  • Aged
  • Physical Functional Performance
  • Leucine/therapeutic use
  • PREVALENCE
  • SUPPLEMENTATION
  • INTERVENTIONS
  • BIOELECTRICAL-IMPEDANCE ANALYSIS
  • SKELETAL-MUSCLE MASS
  • ADULTS
  • ELDERLY-PEOPLE
  • LOWER-EXTREMITY FUNCTION
  • Randomized controlled trial
  • DOUBLE-BLIND
  • ASSOCIATION

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