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Background: Angiotensin-converting enzyme inhibitors and leucine are promising potential treatments for sarcopenia. Neither has yet been tested in adequately powered randomised trials in patients with sarcopenia., Objectives: To determine the efficacy of leucine and perindopril in improving physical function in older people with sarcopenia, to evaluate the effect of leucine and perindopril on muscle mass and to evaluate the predictive biomarkers of sarcopenia., Design: A placebo-controlled, parallel group, double-blind, randomised 2 × 2 factorial trial., Setting: Primary care and geriatric medicine secondary care departments in 14 UK centres., Participants: Adults aged ≥ 70 years with low muscle strength and mass, without contraindications to angiotensin-converting enzyme inhibitors and without known diagnosis-specific skeletal myopathy., Interventions: Eligible participants were randomised 1 : 1 to receive 4 mg of oral perindopril or a matching placebo and, separately, were randomised 1 : 1 to receive 2.5 g of oral leucine powder or a matching placebo powder taken thrice daily with meals. Randomisation was performed using an interactive web-based randomisation system run independently of the research team to preserve allocation concealment., Main Outcome Measures: The primary outcome was the between-group difference in the Short Physical Performance Battery (SPPB) score over the 12-month follow-up period. Other outcome measures included appendicular muscle mass, EQ-5D (EuroQol-5 Dimensions) quality-of-life score, grip strength, quadriceps strength, 6-minute walk distance, activities of daily living, hip bone mineral density and insulin resistance. All adverse events and falls were recorded. Protein-, DNA (deoxyribonucleic acid)- and RNA (ribonucleic acid)-based biomarkers were collected at baseline and at 3 and 12 months., Results: We screened 320 people and randomised 145 participants. Participants had a mean age of 79 (standard deviation 6) years, 78 (54%) were women and the mean SPPB was 7.0 (standard deviation 2.4). The median adherence was lower for perindopril than for placebo (76% vs. 96%; p  < 0.001). Perindopril did not improve the primary outcome (adjusted treatment effect –0.1 points, 95% confidence interval –1.2 to 1.0 points). Quality of life was worse in the perindopril group (treatment effect –12 points, 95% confidence interval –21 to –3 points) and more adverse events occurred in the perindopril group ( n  = 218 vs. n  = 165). Falls rates between the groups were similar and other secondary outcomes showed no significant treatment effect. For leucine compared with placebo, 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% confidence interval –1.0 to 1.1 points). No significant treatment effect was found for any secondary outcome. There were similar numbers of adverse events and falls in both groups., Limitations: The trial did not reach its original recruitment target; this trial alone cannot confidently exclude clinically important effects of either perindopril or leucine., Future Work: Further exploration of biomarkers predicting response to sarcopenia interventions is warranted., Conclusions: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis confirmed the lack of efficacy of both treatments in improving physical performance., Study Registration: This trial is registered as ISRCTN90094835 and EudraCT 2014-003455-61. The systematic review is registered as PROSPERO CRD42014013398., Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation ; Vol. 9, No. 8. See the NIHR Journals Library website for further project information., (Copyright © 2022 Witham et al. This work was produced by Witham et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This is an Open Access publication distributed under the terms of the Creative Commons Attribution CC BY 4.0 licence, which permits unrestricted use, distribution, reproduction and adaption in any medium and for any purpose provided that it is properly attributed. See: https://creativecommons.org/licenses/by/4.0/. For attribution the title, original author(s), the publication source – NIHR Journals Library, and the DOI of the publication must be cited.)

Background: In 2016, 26% of UK men were estimated to be obese. Systematic reviews suggest that few men engage in formal weight loss interventions that support weight reduction and improve health., Objective: To co-produce, with patient and public involvement, an acceptable and feasible randomised controlled trial design to test a men-only weight management intervention., Design: This was a two-phase feasibility study. Phase 1 was the development of intervention components, study procedures and materials including a discrete choice experiment with survey questions. Phase 2 was an individually randomised three-arm feasibility trial over 12 months. Qualitative interviews were conducted at 3 and 12 months., Setting: The setting was two sites in Scotland that had disadvantaged urban and rural areas and differed in employment levels and ethnic groups., Participants: In phase 1, 1045 men with obesity were recruited by Ipsos MORI (London, UK; www.ipsos.com/ipsos-mori/en-uk) to represent the UK population. In phase 2, 105 men with obesity were recruited in the community or through general practice obesity registers. Qualitative interviews were conducted with 50 men at 3 months and with 33 men at 12 months., Interventions: The trial arms were narrative short message service (SMS) for 12 months (SMS only), financial endowment incentive informed by loss aversion and linked to achievement of weight loss targets plus narrative SMS for 12 months (SMS + I), and waiting list control group for 12 months followed by 3 months of an alternative SMS style developed based on feedback from men who had received the narrative SMS (control)., Main Outcome Measures: The main outcome measures were acceptability and feasibility of recruitment, retention, engagement, intervention components and trial procedures. Outcomes were assessed by examining procedural, quantitative and qualitative data at 3, 6 and 12 months., Results: The most acceptable incentive strategy, based on the discrete choice experiment results, was to verify weight loss of 5% at 3 months, verify weight loss of 10% at 6 months and maintain weight loss of 10% at 12 months. Overall, 105 men with obesity from across the socioeconomic spectrum were successfully recruited to target, 59% of whom lived in more disadvantaged areas. Retention at 12 months was acceptable (74%) and was higher among individuals from disadvantaged areas. Narrative SMS were acceptable to many men, with a minority reporting negative reactions. Incentives were acceptable but were not the primary motivation for behaviour change. Twelve men in the incentive arm (33%) secured at least some money and three (8%) secured the full amount. Both intervention arms lost some weight, with greater weight loss in the arm that received SMS and incentives. The alternative SMS based on men’s feedback received no strong negative reactions., Limitations: Fewer participants from the SMS + I arm (64%) completed the study at 12 months than did those in the SMS-only (79%) and control (83%) arms. The reasons for this difference were complex., Conclusions: The men-only weight management intervention consisting of narrative SMS and financial incentives was acceptable and feasible, meeting the progression criteria for a full trial. Tailoring of SMS may improve acceptability and retention., Future Work: Minor refinements to the intervention components based on the study findings will be made prior to testing in a multisite definitive randomised controlled trial., Trial Registration: ClinicalTrials.gov NCT03040518., Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research ; Vol. 8, No. 11. See the NIHR Journals Library website for further project information., (Copyright © Queen’s Printer and Controller of HMSO 2020. This work was produced by Dombrowski et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.)