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1. Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Author

Chalmers, James, Abo-Leyah, Hani, New, Benjamin JM, Almaden-Boyle, Christine, Connell, David, Taylor, Jennifer, Strachan, Jodie, Loftus, Heather, Young, Lesley, Strachan, Angela, Band, Margaret, McLaren-Neil, Fiona, Pilvinyte, Kristina, Adamson, Simon, Lahnsteiner, Eva, Rauchhaus, Petra, Hogarth, Fiona, George, Jacob, Burns, Tricia, Coote, Elizabeth, Keiller, Marney, Patel, Manish, Smith, Andrew, Sage, Elizabeth, Cooper, Jamie, Miller, David, Dosanjh, Davinder, Sutton, Benjamin, Underwood, Jonathan, Frayling, Sharon, Haynes, Matthew, Broad, Lauren, Jones, Laura, Rahilly, Karen, Oliver, Catherine, Evans, Terriann, Balan, Andrea, Davies, Rhys, Forde, Donal, Nye, Clemency, Haboubi, Dr, Hilton, Zoe, Williams, Jennie, McQueen, Alison, Spears, Mark, Edmond, Ian, Salutous, Dario, McGenily, Laura, Scott, Rhona, Henderson, Eilidh, Collins, Andrea, Dhasmana, Devesh, Liu, Patrick, Morrow, Ana, Couser, Mandy, Davey, Fleur, Hicks, Alexander, Wiffen, Laura, Fox, Lauren, Abdelrahim, Mohamed, Darbyshire, Alexander, Cowen, Elena, Rowley, Megan, Giles, Benjamin, Yang, Yingjia, Brown, Tom, Rupani, Hitasha, Hawes, Elizabeth, Barnes, Debi, Brogan, Fiona, Bungue-Tuble, Roneleeh, Howe, Serena, Turner, Charlotte, Baryschpolec, Sonia, Longhurst, Bev, Moon, Maria, Watkins, Lynn, Baker-Moffat, Michelle, Murray, Lisa, Harrington-Davies, Yasmin, Burrows, Kate, Minnis, Chrissie, Wands, Mary, Bamgboye, Adefunke, Wong, Charlotte, Brightling, Christopher, Diver, Sarah, Russell, Richard, McAuley, Hamish, Elneima, Omer, Yousuf, Ahmed, McCourt, Paula, Hargadon, Beverley, Parker, Sarah, Bourne, Michelle, Suntharalingam, Jay, Hartley, Tom, Masan, Vidan, Sturney, Sharon, MacKenzie, Rob, Marchand, Clare, Mason, Rebecca, White, Katie, Kirby, Alison, Meda, Manjula, Diwakar, Lavanya, Russell, Peter, Finn, Joanne, Harris, Sophie, Muir, Carol, Cook, Gemma, Staines, Nikki, Cook, Chris, Thompson, AA Roger, Condliffe, Alison, Hull, Rebecca, Dowey, Rebecca, Turton, Helena, Collini, Paul, Gabriel, Zoé, Hardman, Simon, Newell, Helen, Middle, Janet, Simpson, Phillip, Colton, Hayley, Barker, Joann, Birchall, Katie, Harrington, Kate, Housley, Kay, Lenagh, Rebecca, Wilson, Jayne, Wesonga, Joan, Whitham, Rachel, Bird, Sarah, Jackson, Yvonne, Mbuyisa, Angeline, Anderson, Samantha, Wilson, Anna, Kibutu, Faith, Walker, Sara, Cawthron, Kay, Macharia, Irene, Smart, Lynne, Emery, Anna, Howell, Alice, Hurditch, Elizabeth, Ford, Amber, Turner, Kim, Watson, Lisa, Bowler, Helen, Jackson, Tracy, Jaques, Carol, Dyer, Nichole, Ducker, Shelley, Goodall, Vicky, Udale, Emily, Keir, Holly R, Long, Merete B, Giam, Yan Hui, Vadiveloo, Thenmalar, Pembridge, Thomas, Hull, Rebecca C, Delgado, Lilia, Gilmour, Amy, Hughes, Chloe, Richardson, Hollian, Cassidy, Diane, Dosanjh, Davinder PS, Sage, Beth, Condliffe, Alison M, Shoemark, Amelia, MacLennan, Graeme, and Chalmers, James D

Published
2022
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2. Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia—Analyses from the LACE randomised controlled trial

Author

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

Published
2023
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3. ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial

Author

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

Published
2023
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4. Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial

Author

Keir, Holly R, primary, Long, Merete B, additional, Abo-Leyah, Hani, additional, Giam, Yan Hui, additional, Vadiveloo, Thenmalar, additional, Pembridge, Thomas, additional, Hull, Rebecca C, additional, Delgado, Lilia, additional, Band, Margaret, additional, McLaren-Neil, Fiona, additional, Adamson, Simon, additional, Lahnsteiner, Eva, additional, Gilmour, Amy, additional, Hughes, Chloe, additional, New, Benjamin JM, additional, Connell, David, additional, Dowey, Rebecca, additional, Turton, Helena, additional, Richardson, Hollian, additional, Cassidy, Diane, additional, Cooper, Jamie, additional, Suntharalingam, Jay, additional, Diwakar, Lavanya, additional, Russell, Peter, additional, Underwood, Jonathan, additional, Hicks, Alexander, additional, Dosanjh, Davinder PS, additional, Sage, Beth, additional, Dhasmana, Devesh, additional, Spears, Mark, additional, Thompson, AA Roger, additional, Brightling, Christopher, additional, Smith, Andrew, additional, Patel, Manish, additional, George, Jacob, additional, Condliffe, Alison M, additional, Shoemark, Amelia, additional, MacLennan, Graeme, additional, Chalmers, James D, additional, Chalmers, James, additional, Almaden-Boyle, Christine, additional, Taylor, Jennifer, additional, Strachan, Jodie, additional, Loftus, Heather, additional, Young, Lesley, additional, Strachan, Angela, additional, Pilvinyte, Kristina, additional, Rauchhaus, Petra, additional, Hogarth, Fiona, additional, Burns, Tricia, additional, Coote, Elizabeth, additional, Keiller, Marney, additional, Sage, Elizabeth, additional, Miller, David, additional, Dosanjh, Davinder, additional, Sutton, Benjamin, additional, Frayling, Sharon, additional, Haynes, Matthew, additional, Broad, Lauren, additional, Jones, Laura, additional, Rahilly, Karen, additional, Oliver, Catherine, additional, Evans, Terriann, additional, Balan, Andrea, additional, Davies, Rhys, additional, Forde, Donal, additional, Nye, Clemency, additional, Haboubi, Dr, additional, Hilton, Zoe, additional, Williams, Jennie, additional, McQueen, Alison, additional, Edmond, Ian, additional, Salutous, Dario, additional, McGenily, Laura, additional, Scott, Rhona, additional, Henderson, Eilidh, additional, Collins, Andrea, additional, Liu, Patrick, additional, Morrow, Ana, additional, Couser, Mandy, additional, Davey, Fleur, additional, Wiffen, Laura, additional, Fox, Lauren, additional, Abdelrahim, Mohamed, additional, Darbyshire, Alexander, additional, Cowen, Elena, additional, Rowley, Megan, additional, Giles, Benjamin, additional, Yang, Yingjia, additional, Brown, Tom, additional, Rupani, Hitasha, additional, Hawes, Elizabeth, additional, Barnes, Debi, additional, Brogan, Fiona, additional, Bungue-Tuble, Roneleeh, additional, Howe, Serena, additional, Turner, Charlotte, additional, Baryschpolec, Sonia, additional, Longhurst, Bev, additional, Moon, Maria, additional, Watkins, Lynn, additional, Baker-Moffat, Michelle, additional, Murray, Lisa, additional, Harrington-Davies, Yasmin, additional, Burrows, Kate, additional, Minnis, Chrissie, additional, Wands, Mary, additional, Bamgboye, Adefunke, additional, Wong, Charlotte, additional, Diver, Sarah, additional, Russell, Richard, additional, McAuley, Hamish, additional, Elneima, Omer, additional, Yousuf, Ahmed, additional, McCourt, Paula, additional, Hargadon, Beverley, additional, Parker, Sarah, additional, Bourne, Michelle, additional, Hartley, Tom, additional, Masan, Vidan, additional, Sturney, Sharon, additional, MacKenzie, Rob, additional, Marchand, Clare, additional, Mason, Rebecca, additional, White, Katie, additional, Kirby, Alison, additional, Meda, Manjula, additional, Finn, Joanne, additional, Harris, Sophie, additional, Muir, Carol, additional, Cook, Gemma, additional, Staines, Nikki, additional, Cook, Chris, additional, Condliffe, Alison, additional, Hull, Rebecca, additional, Collini, Paul, additional, Gabriel, Zoé, additional, Hardman, Simon, additional, Newell, Helen, additional, Middle, Janet, additional, Simpson, Phillip, additional, Colton, Hayley, additional, Barker, Joann, additional, Birchall, Katie, additional, Harrington, Kate, additional, Housley, Kay, additional, Lenagh, Rebecca, additional, Wilson, Jayne, additional, Wesonga, Joan, additional, Whitham, Rachel, additional, Bird, Sarah, additional, Jackson, Yvonne, additional, Mbuyisa, Angeline, additional, Anderson, Samantha, additional, Wilson, Anna, additional, Kibutu, Faith, additional, Walker, Sara, additional, Cawthron, Kay, additional, Macharia, Irene, additional, Smart, Lynne, additional, Emery, Anna, additional, Howell, Alice, additional, Hurditch, Elizabeth, additional, Ford, Amber, additional, Turner, Kim, additional, Watson, Lisa, additional, Bowler, Helen, additional, Jackson, Tracy, additional, Jaques, Carol, additional, Dyer, Nichole, additional, Ducker, Shelley, additional, Goodall, Vicky, additional, and Udale, Emily, additional

Published
2022
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5. Leucine and perindopril to improve physical performance in people over 70 years with sarcopenia: the LACE factorial RCT

Author

Witham, Miles D, primary, Adamson, Simon, additional, Avenell, Alison, additional, Band, Margaret M, additional, Bashir, Tufail, additional, Donnan, Peter T, additional, George, Jacob, additional, Hapca, Adrian, additional, Hume, Cheryl, additional, Kemp, Paul, additional, McKenzie, Emma, additional, Pilvinyte, Kristina, additional, Rossios, Christos, additional, Smith, Karen, additional, Struthers, Allan D, additional, and Sumukadas, Deepa, additional

Published
2022
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6. Recruitment strategies for sarcopenia trials: lessons from the LACE randomized controlled trial

Author

Witham, Miles D., primary, Achison, Marcus, additional, Aspray, Terry J., additional, Avenell, Alison, additional, Band, Margaret M., additional, Donnan, Peter T., additional, George, Jacob, additional, Hapca, Adrian, additional, Hume, Cheryl, additional, Kemp, Paul, additional, Pilvinyte, Kristina, additional, Sayer, Avan A., additional, Smith, Karen T., additional, Struthers, Allan D., additional, and Sumukadas, Deepa, additional

Published
2021
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7. Asthma prescribing according to Arg16Gly beta-2 genotype: a randomised trial in adolescents

Author

Ruffles, Tom, primary, Jones, Christina J., additional, Palmer, Colin, additional, Turner, Steve, additional, Grigg, Jonathan, additional, Tavendale, Roger, additional, Hogarth, Fiona, additional, Rauchhaus, Petra, additional, Pilvinyte, Kristina, additional, Hannah, Romanie, additional, Smith, Helen, additional, Littleford, Roberta, additional, Lipworth, Brian, additional, and Mukhopadhyay, Somnath, additional

Published
2021
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8. Effect of controller prescribing according to rs1042713 genotype on asthma related quality of life in young people (PACT): a randomized controlled trial

Author

Ruffles, Thomas, primary, Jones, Christina, additional, Palmer, Colin, additional, Turner, Steve, additional, Grigg, Jonathan, additional, Tavendale, Roger, additional, Hogarth, Fiona, additional, Rauchhaus, Petra, additional, Pilvinyte, Kristina, additional, Smith, Helen, additional, Littleford, Roberta, additional, Lipworth, Brian, additional, and Mukhopadhyay, Somnath, additional

Published
2020
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9. Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Author

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

Abstract

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, 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. 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)]. 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.

Published
2022
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10. Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

Author

Shrestha A, Bashir T, Achison M, Adamson S, Akpan A, Aspray T, Avenell A, Band MM, Burton LA, Cvoro V, Donnan PT, Duncan GW, George J, Gordon AL, Gregson CL, Hapca A, Hume C, Jackson TA, Kerr S, Kilgour A, Masud T, McKenzie A, McKenzie E, Patel H, Pilvinyte K, Roberts HC, Sayer AA, Rossios C, Smith KT, Soiza RL, Steves CJ, Struthers AD, Tiwari D, Whitney J, Witham MD, and Kemp PR

Subjects
Humans, Male, Aged, Female, Muscle, Skeletal pathology, Muscle, Skeletal physiopathology, Genotype, Alleles, Polymorphism, Single Nucleotide, Body Composition, Leucine genetics, Aged, 80 and over, Hand Strength, Muscle Strength genetics, Receptor, Bradykinin B2 genetics, Sarcopenia genetics, Physical Functional Performance
Abstract

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia., Methods: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures., Results: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019)., Conclusion: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shrestha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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11. Leucine and perindopril to improve physical performance in people over 70 years with sarcopenia: the LACE factorial RCT

Author

Witham MD, Adamson S, Avenell A, Band MM, Bashir T, Donnan PT, George J, Hapca A, Hume C, Kemp P, McKenzie E, Pilvinyte K, Rossios C, Smith K, Struthers AD, and Sumukadas D

Abstract

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.)

Published
2022
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