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

被引:29
作者
Achison, Marcus [1 ,2 ]
Adamson, Simon [1 ,2 ]
Akpan, Asangaedem [3 ]
Aspray, Terry [4 ,5 ]
Avenell, Alison [6 ]
Band, Margaret M. [1 ,2 ]
Bashir, Tufail [7 ]
Burton, Louise A. [8 ,9 ]
Cvoro, Vera [10 ,11 ]
Donnan, Peter T. [12 ]
Duncan, Gordon W. [13 ]
George, Jacob [11 ,14 ]
Gordon, Adam L. [15 ,16 ,17 ]
Gregson, Celia L. [18 ,19 ]
Hapca, Adrian [1 ,2 ]
Henderson, Emily [20 ,21 ]
Hume, Cheryl [1 ,2 ]
Jackson, Thomas A. [22 ]
Kemp, Paul [7 ]
Kerr, Simon [23 ]
Kilgour, Alixe [13 ]
Lyell, Veronica [1 ,2 ]
Masud, Tahir [24 ]
McKenzie, Andrew [1 ,2 ]
McKenzie, Emma [1 ,2 ]
Patel, Harnish [25 ,26 ]
Pilvinyte, Kristina [1 ,2 ]
Roberts, Helen C. [27 ]
Rossios, Christos [7 ]
Sayer, Avan A. [4 ,5 ]
Smith, Karen T. [1 ,2 ]
Soiza, Roy L. [28 ]
Steves, Claire J. [29 ,30 ]
Struthers, Allan D. [31 ]
Sumukadas, Deepa [32 ]
Tiwari, Divya [33 ,34 ]
Whitney, Julie [35 ,36 ]
Witham, Miles D. [4 ,5 ]
机构
[1] Univ Dundee, Ninewells Hosp, Tayside Med Sci Ctr TASC, Tayside Clin Trials Unit TCTU, Dundee, Scotland
[2] Med Sch, Dundee, Scotland
[3] Univ Liverpool, Liverpool Univ Hosp NHS FT Trust, Clin Res Network Northwest Coast, Liverpool, Merseyside, England
[4] Newcastle Univ, NIHR Newcastle Biomed Res Ctr, Translat Clin Res Inst, AGE Res Grp, Newcastle Upon Tyne, Tyne & Wear, England
[5] Newcastle Upon Tyne NHS Trust, Newcastle Upon Tyne, Tyne & Wear, England
[6] Univ Aberdeen, Hlth Serv Res Unit, Aberdeen, Scotland
[7] Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc & Resp Interface Sect, South Kensington Campus, London, England
[8] Univ Dundee, Med Elderly, Dundee, Scotland
[9] Univ Dundee, Ageing & Hlth, Dundee, Scotland
[10] Victoria Hosp, Kirkcaldy, Scotland
[11] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland
[12] Univ Dundee, Sch Med, Div Populat Hlth & Genom, Dundee, Scotland
[13] NHS Lothian, Med Elderly, Edinburgh, Midlothian, Scotland
[14] Univ Dundee, Ninewells Hosp, Dept Clin Pharmacol, Div Mol & Clin Med,Med Sch, Dundee, Scotland
[15] Univ Nottingham, Sch Med, Unit Injury Inflammat & Recovery, Nottingham, England
[16] NIHR Nottingham Biomed Res Ctr, Nottingham, England
[17] Univ Hosp Derby & Burton NHS Fdn Trust, Dept Med Elderly, Derby, England
[18] Univ Bristol, Bristol Med Sch, Musculoskeletal Res Unit, Bristol, Avon, England
[19] Royal United Hosp NHS Fdn Trust Bath, Older Persons Unit, Bath, Avon, England
[20] Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England
[21] Royal United Hosp Bath NHS Fdn Trust, Bath, Avon, England
[22] Univ Birmingham, Inst Inflammat & Ageing, Birmingham, W Midlands, England
[23] Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Older Peoples Med, Newcastle Upon Tyne, Tyne & Wear, England
[24] Nottingham Univ Hosp NHS Trust, Clin Gerontol Res Unit, City Hosp Campus, Nottingham, England
[25] Univ Southampton, NIHR Biomed Res Ctr, Southampton, Hants, England
[26] Univ Hosp Southampton NHSFT, Southampton, Hants, England
[27] Univ Southampton, Mailpoint Southampton Gen Hosp 807, Acad Geriatr Med, Southampton, Hants, England
[28] Univ Aberdeen, Ageing & Clin Expt Res ACER Grp, Aberdeen, Scotland
[29] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England
[30] Kings Coll Hosp London, Dept Clin Gerontol, London, England
[31] Univ Dundee, Ninewells Hosp, Div Mol & Clin Med, Dundee, Scotland
[32] NHS Tayside, Dept Med Elderly, Dundee, Scotland
[33] Bournemouth Univ, Bournemouth, Dorset, England
[34] Royal Bournemouth Hosp, Bournemouth, Dorset, England
[35] Kings Coll London, Sch Populat Hlth & Environm Sci, London, England
[36] Kings Coll Hosp London, London, England
关键词
Angiotensin converting enzyme inhibitor; Leucine; Sarcopenia; Randomized controlled trial; BIOELECTRICAL-IMPEDANCE ANALYSIS; LOWER-EXTREMITY FUNCTION; SKELETAL-MUSCLE MASS; ELDERLY-PEOPLE; DOUBLE-BLIND; ADULTS; SUPPLEMENTATION; PREVALENCE; INTERVENTIONS; ASSOCIATION;
D O I
10.1002/jcsm.12934
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
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页码:858 / 871
页数:14
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