OBJECTIVE: To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. DESIGN: Evaluator blinded, randomised controlled trial. SETTING: 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. PARTICIPANTS: 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). INTERVENTIONS: The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. MAIN OUTCOME MEASURES: The primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes. RESULTS: Mean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34). CONCLUSIONS: A multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.

1st Faculty of Medicine Univerzita Karlova Praha Prague Czech Republic

Astellas Pharma Tokyo Japan

Bluecompanion London UK

Cognitive and Motor Centre Medicine and Geriatric Rehabilitation Department of Parma University Hospital of Parma Parma Italy

Department of Cardiology and Berlin Institute of Health Centre for Regenerative Therapies German Centre for Cardiovascular Research partner site Berlin Charité Universitätsmedizin Berlin Berlin Germany

Department of Cardiology and Pneumology University of Goettingen Medical Centre Goettingen Germany

Department of Clinical Sciences and Community Health Università di Milano Milan Italy

Department of Geriatrics and Orthopaedics Università Cattolica del Sacro Cuore Rome Italy

Department of Geriatrics Landspitali University Hospital Faculty of Medicine University of Iceland Reykjavik Iceland

Department of Internal Medicine and Gerontology Uniwersytet Jagiellonski Collegium Medicum Faculty of Medicine Krakow Poland

Department of Internal Medicine Medizinische Universität Graz Graz Austria

Department of Medical Statistics University of Goettingen Medical Centre Goettingen Germany

Department of Medicine and Surgery Università degli Studi di Parma Parma Italy

Department of Respiratory Medicine NUTRIM School of Nutrition and Translational Research in Metabolism Universiteit Maastricht Maastricht Netherlands

Diabetes Frail Droitwich Spa UK

Fondazione Policlinico Universitario Agostino Gemelli IRCCS Rome Italy

Geriatric Intensive Care Medicine Università degli Studi di Firenze and Azienda Ospedaliero Universitaria Careggi Florence Italy

Geriatric Unit IRCCS Istituti Clinici Scientifici Maugeri Milan Italy

German Centre for Cardiovascular Research partner site Göttingen Goettingen Germany

Gérontopôle Centre Hospitalier Universitaire de Toulouse Toulouse France

Institute for Biomedicine of Aging Friedrich Alexander Universität Erlangen Nürnberg Nurnberg Germany

Institute on Aging University of Florida Gainesville FL USA

International Clinical Trial Research Department Servier Madrid Spain

IRCCS INRCA Ancona Italy

Pôle Gérontologie Clinique Centre Hospitalier Universitaire de Limoges Limoges France

Sanofi Aventis R and D Chilly Mazarin France

Servicio de Geriatría Hospital Universitario de Getafe Getafe Spain

Servicio de Geriatría Hospital Universitario Ramón y Cajal IRYCIS Madrid Spain

Silesian Hospital in Opava Opava Czech Republic

Translational Medicine and Clinical Pharmacology Boehringer Ingelheim Pharma Biberach an der Riss Germany

Translational Medicine Novartis Institutes for Biomedical Research Basel Switzerland

Translational Medicine Novartis Institutes for Biomedical Research Cambridge MA USA

University of Helsinki and Helsinki University Hospital Helsinki Finland

University of Oulu Centre for Life Course Health Research Oulo Finland

BMJ. 2022 May 11;377:o1084. doi: 10.1136/bmj.o1084. PubMed

Ann Intern Med. 2022 Sep;175(9):JC103. doi: 10.7326/J22-0062. PubMed

Zobrazit více v PubMed

Newman AB, Simonsick EM, Naydeck BL, et al. . Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA 2006;295:2018-26. 10.1001/jama.295.17.2018. PubMed DOI

Studenski S, Perera S, Patel K, et al. . Gait speed and survival in older adults. JAMA 2011;305:50-8. 10.1001/jama.2010.1923. PubMed DOI PMC

Hardy SE, Kang Y, Studenski SA, Degenholtz HB. Ability to walk 1/4 mile predicts subsequent disability, mortality, and health care costs. J Gen Intern Med 2011;26:130-5. 10.1007/s11606-010-1543-2. PubMed DOI PMC

Chen LK, Hwang AC, Lee WJ, et al. Taiwan Health Promotion Intervention Study for Elders research group . Efficacy of multidomain interventions to improve physical frailty, depression and cognition: data from cluster-randomized controlled trials. J Cachexia Sarcopenia Muscle 2020;11:650-62. 10.1002/jcsm.12534. PubMed DOI PMC

Innovative Medicines Initiative. 9th call for proposals 2013 – Innovative Medicines Initiative. July 2013. https://www.imi.europa.eu/sites/default/files/uploads/documents/apply-for-funding/call-documents/imi1/Calll_9_Text.pdf (accessed 2 Mar 2022)

Landi F, Cherubini A, Cesari M, et al. . Sarcopenia and frailty: From theoretical approach into clinical practice. Eur Geriatr Med 2016;7:197-200. 10.1016/j.eurger.2015.12.015. DOI

Cesari M, Landi F, Calvani R, et al. SPRINTT Consortium . Rationale for a preliminary operational definition of physical frailty and sarcopenia in the SPRINTT trial. Aging Clin Exp Res 2017;29:81-8. 10.1007/s40520-016-0716-1. PubMed DOI

Marzetti E, Cesari M, Calvani R, et al. SPRINTT Consortium . The “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” (SPRINTT) randomized controlled trial: Case finding, screening and characteristics of eligible participants. Exp Gerontol 2018;113:48-57. 10.1016/j.exger.2018.09.017. PubMed DOI

Landi F, Cesari M, Calvani R, et al. SPRINTT Consortium . The “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” (SPRINTT) randomized controlled trial: design and methods. Aging Clin Exp Res 2017;29:89-100. 10.1007/s40520-016-0715-2. PubMed DOI

Guralnik JM, Simonsick EM, Ferrucci L, et al. . A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85-94. 10.1093/geronj/49.2.M85. PubMed DOI

McLean RR, Shardell MD, Alley DE, et al. . Criteria for clinically relevant weakness and low lean mass and their longitudinal association with incident mobility impairment and mortality: the foundation for the National Institutes of Health (FNIH) sarcopenia project. J Gerontol A Biol Sci Med Sci 2014;69:576-83. 10.1093/gerona/glu012 PubMed DOI PMC

Simonsick EM, Montgomery PS, Newman AB, Bauer DC, Harris T. Measuring fitness in healthy older adults: the Health ABC Long Distance Corridor Walk. J Am Geriatr Soc 2001;49:1544-8. 10.1046/j.1532-5415.2001.4911247.x. PubMed DOI

Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98. 10.1016/0022-3956(75)90026-6. PubMed DOI

Fielding RA, Rejeski WJ, Blair S, et al. LIFE Research Group . The lifestyle interventions and independence for elders study: Design and methods. J Gerontol A Biol Sci Med Sci 2011;66:1226-37. 10.1093/gerona/glr123 PubMed DOI PMC

Borg G. Perceived exertion as an indicator of somatic stress. Scand J Rehabil Med 1970;2:92-8. PubMed

Volkert D, Beck AM, Cederholm T, et al. . ESPEN guideline on clinical nutrition and hydration in geriatrics. Clin Nutr 2019;38:10-47. 10.1016/j.clnu.2018.05.024. PubMed DOI

Pahor M, Guralnik JM, Ambrosius WT, et al. LIFE study investigators . Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 2014;311:2387-96. 10.1001/jama.2014.5616. PubMed DOI PMC

Abellan van Kan G, Rolland Y, Andrieu S, et al. . Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging 2009;13:881-9. 10.1007/s12603-009-0246-z. PubMed DOI

Liu CK, Leng X, Hsu FC, et al. . The impact of sarcopenia on a physical activity intervention: the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P). J Nutr Health Aging 2014;18:59-64. 10.1007/s12603-013-0369-0. PubMed DOI PMC

Perera S, Mody SH, Woodman RC, Studenski SA. Meaningful change and responsiveness in common physical performance measures in older adults. J Am Geriatr Soc 2006;54:743-9. 10.1111/j.1532-5415.2006.00701.x. PubMed DOI

Kwon S, Perera S, Pahor M, et al. . What is a meaningful change in physical performance? Findings from a clinical trial in older adults (the LIFE-P study). J Nutr Health Aging 2009;13:538-44. 10.1007/s12603-009-0104-z. PubMed DOI PMC

Rodriguez-Mañas L, Laosa O, Vellas B, et al. European MID-Frail Consortium . Effectiveness of a multimodal intervention in functionally impaired older people with type 2 diabetes mellitus. J Cachexia Sarcopenia Muscle 2019;10:721-33. 10.1002/jcsm.12432. PubMed DOI PMC

Casas-Herrero Á, Sáez de Asteasu ML, Antón-Rodrigo I, et al. . Effects of Vivifrail multicomponent intervention on functional capacity: a multicentre, randomized controlled trial. J Cachexia Sarcopenia Muscle 2022;13:884-93. 10.1002/jcsm.12925. PubMed DOI PMC

Jang IY, Jung HW, Park H, et al. . A multicomponent frailty intervention for socioeconomically vulnerable older adults: a designed-delay study. Clin Interv Aging 2018;13:1799-814. 10.2147/CIA.S177018. PubMed DOI PMC

Kitzman DW, Whellan DJ, Duncan P, et al. . Physical rehabilitation for older patients hospitalized for heart failure. N Engl J Med 2021;385:203-16. 10.1056/NEJMoa2026141. PubMed DOI PMC

Zhang Y, Zou L, Chen ST, et al. . Effects and moderators of exercise on sarcopenic components in sarcopenic elderly: A systematic review and meta-analysis. Front Med (Lausanne) 2021;8:649748. 10.3389/fmed.2021.649748. PubMed DOI PMC

Chen N, He X, Feng Y, Ainsworth BE, Liu Y. Effects of resistance training in healthy older people with sarcopenia: a systematic review and meta-analysis of randomized controlled trials. Eur Rev Aging Phys Act 2021;18:23. 10.1186/s11556-021-00277-7. PubMed DOI PMC

Elstgeest LEM, Schaap LA, Heymans MW, et al. Health ABC Study . Sex-and race-specific associations of protein intake with change in muscle mass and physical function in older adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr 2020;112:84-95. 10.1093/ajcn/nqaa099. PubMed DOI PMC

European Medicines Agency. Reflection paper on physical frailty: instruments for baseline characterisation of older populations in clinical trials. January 2018. www.ema.europa.eu/documents/scientific-guideline/reflection-paper-physical-frailty-instruments-baseline-characterisation-older-populations-clinical_en.pdf (accessed 2 Mar 2022)

Arrieta H, Astrugue C, Regueme S, et al. . Effects of a physical activity programme to prevent physical performance decline in onco-geriatric patients: a randomized multicentre trial. J Cachexia Sarcopenia Muscle 2019;10:287-97. 10.1002/jcsm.12382. PubMed DOI PMC

Rooks D, Swan T, Goswami B, et al. . Bimagrumab vs optimized standard of care for treatment of sarcopenia in community-dwelling older adults: A randomized clinical trial. JAMA Netw Open 2020;3:e2020836. 10.1001/jamanetworkopen.2020.20836. PubMed DOI PMC

Ngandu T, Lehtisalo J, Solomon A, et al. . A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 2015;385:2255-63. 10.1016/S0140-6736(15)60461-5. PubMed DOI

Patrizio E, Calvani R, Marzetti E, Cesari M. Physical functional assessment in older adults. J Frailty Aging 2021;10:141-9. 10.14283/jfa.2020.61. PubMed DOI

Rolland YM, Cesari M, Miller ME, Penninx BW, Atkinson HH, Pahor M. Reliability of the 400-m usual-pace walk test as an assessment of mobility limitation in older adults. J Am Geriatr Soc 2004;52:972-6. 10.1111/j.1532-5415.2004.52267.x. PubMed DOI

Dent E, Morley JE, Cruz-Jentoft AJ, et al. . Physical frailty: ICFSR international clinical practice guidelines for identification and management. J Nutr Health Aging 2019;23:771-87. 10.1007/s12603-019-1273-z. PubMed DOI PMC

Izquierdo M, Merchant RA, Morley JE, et al. . International exercise recommendations in older adults (ICFSR): Expert consensus guidelines. J Nutr Health Aging 2021;25:824-53. 10.1007/s12603-021-1665-8. PubMed DOI

Niemeijer A, Lund H, Stafne SN, et al. . Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis. Br J Sports Med 2020;54:1073-80. 10.1136/bjsports-2018-100461. PubMed DOI

Gielen E, Beckwée D, Delaere A, De Breucker S, Vandewoude M, Bautmans I, Sarcopenia Guidelines Development Group of the Belgian Society of Gerontology and Geriatrics (BSGG) . Nutritional interventions to improve muscle mass, muscle strength, and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Nutr Rev 2021;79:121-47. 10.1093/nutrit/nuaa011. PubMed DOI

Ferrucci L, Kuchel GA. Heterogeneity of aging: Individual risk factors, mechanisms, patient priorities, and outcomes. J Am Geriatr Soc 2021;69:610-2. 10.1111/jgs.17011. PubMed DOI PMC

de Souto Barreto P, Rolland Y, Vellas B, Maltais M. Association of long-term exercise training with risk of falls, fractures, hospitalizations, and mortality in older adults: A systematic review and meta-analysis. JAMA Intern Med 2019;179:394-405. 10.1001/jamainternmed.2018.5406. PubMed DOI PMC

Gill TM, Pahor M, Guralnik JM, et al. LIFE Study Investigators . Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study). BMJ 2016;352:i245. 10.1136/bmj.i245. PubMed DOI PMC

Sherrington C, Whitney JC, Lord SR, Herbert RD, Cumming RG, Close JC. Effective exercise for the prevention of falls: a systematic review and meta-analysis. J Am Geriatr Soc 2008;56:2234-43. 10.1111/j.1532-5415.2008.02014.x. PubMed DOI

Pua YH, Ong PH, Clark RA, Matcher DB, Lim EC. Falls efficacy, postural balance, and risk for falls in older adults with falls-related emergency department visits: prospective cohort study. BMC Geriatr 2017;17:291. 10.1186/s12877-017-0682-2. PubMed DOI PMC

Stenholm S, Shardell M, Bandinelli S, Guralnik JM, Ferrucci L. Physiological factors contributing to mobility loss over 9 years of follow-up—results from the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2015;70:591-7. 10.1093/gerona/glv004. PubMed DOI PMC

Effects of Exercise Training on Muscle Quality in Older Individuals: A Systematic Scoping Review with Meta-Analyses

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ClinicalTrials.gov
NCT02582138