Intended for healthcare professionals

  1. Research
  2. Multicomponent...
  3. Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project)
CCBYNC Open access
Research

Multicomponent intervention to prevent mobility disability in frail older adults: randomised controlled trial (SPRINTT project)

BMJ 2022; 377 doi: https://doi.org/10.1136/bmj-2021-068788 (Published 11 May 2022) Cite this as: BMJ 2022;377:e068788
  1. Roberto Bernabei, professor12,
  2. Francesco Landi, professor12,
  3. Riccardo Calvani, researcher1,
  4. Matteo Cesari, professor34,
  5. Susanna Del Signore, chief executive officer5,
  6. Stefan D Anker, professor6,
  7. Raphael Bejuit, senior biostatistician7,
  8. Philippe Bordes, project manager7,
  9. Antonio Cherubini, professor8,
  10. Alfonso J Cruz-Jentoft, professor9,
  11. Mauro Di Bari, associate professor10,
  12. Tim Friede, professor1112,
  13. Carmen Gorostiaga Ayestarán, director13,
  14. Harmonie Goyeau, biostatistician7,
  15. Pálmi V Jónsson, professor14,
  16. Makoto Kashiwa, director15,
  17. Fabrizia Lattanzio, scientific director8,
  18. Marcello Maggio, professor1617,
  19. Luca Mariotti, project manager2,
  20. Ram R Miller, director18,
  21. Leocadio Rodriguez-Mañas, professor19,
  22. Regina Roller-Wirnsberger, professor20,
  23. Ingrid Rýznarová, head physician21,
  24. Joachim Scholpp, global head22,
  25. Annemie M W J Schols, professor23,
  26. Cornel C Sieber, professor24,
  27. Alan J Sinclair, professor25,
  28. Anna Skalska, professor26,
  29. Timo Strandberg, professor2728,
  30. Achille Tchalla, professor29,
  31. Eva Topinková, professor30,
  32. Matteo Tosato, head geriatrician1,
  33. Bruno Vellas, professor31,
  34. Stephan von Haehling, professor1232,
  35. Marco Pahor, professor33,
  36. Ronenn Roubenoff, global head34,
  37. Emanuele Marzetti, associate professor12
  38. on behalf of the SPRINTT consortium
    1. 1Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy
    2. 2Department of Geriatrics and Orthopaedics, Università Cattolica del Sacro Cuore, Rome, Italy
    3. 3Department of Clinical Sciences and Community Health, Università di Milano, Milan, Italy
    4. 4Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy
    5. 5Bluecompanion, London, UK
    6. 6Department of Cardiology and Berlin Institute of Health Centre for Regenerative Therapies, German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany
    7. 7Sanofi-Aventis R&D, Chilly-Mazarin, France
    8. 8IRCCS INRCA, Ancona, Italy
    9. 9Servicio de Geriatría, Hospital Universitario Ramón y Cajal-IRYCIS, Madrid, Spain
    10. 10Geriatric Intensive Care Medicine, Università degli Studi di Firenze and Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
    11. 11Department of Medical Statistics, University of Goettingen Medical Centre, Goettingen, Germany
    12. 12German Centre for Cardiovascular Research (DZHK) partner site Göttingen, Goettingen, Germany
    13. 13International Clinical Trial Research Department, Servier, Madrid, Spain
    14. 14Department of Geriatrics, Landspitali University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
    15. 15Astellas Pharma, Tokyo, Japan
    16. 16Department of Medicine and Surgery, Università degli Studi di Parma, Parma, Italy
    17. 17Cognitive and Motor Centre, Medicine and Geriatric Rehabilitation Department of Parma, University Hospital of Parma, Parma, Italy
    18. 18Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, MA, USA
    19. 19Servicio de Geriatría, Hospital Universitario de Getafe, Getafe, Spain
    20. 20Department of Internal Medicine, Medizinische Universität Graz, Graz, Austria
    21. 21Silesian Hospital in Opava, Opava, Czech Republic
    22. 22Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma, Biberach an der Riss, Germany
    23. 23Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Universiteit Maastricht, Maastricht, Netherlands
    24. 24Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nurnberg, Germany
    25. 25Diabetes Frail, Droitwich Spa, UK
    26. 26Department of Internal Medicine and Gerontology, Uniwersytet Jagiellonski Collegium Medicum, Faculty of Medicine, Krakow, Poland
    27. 27University of Helsinki and Helsinki University Hospital, Helsinki, Finland
    28. 28University of Oulu, Centre for Life Course Health Research, Oulo, Finland
    29. 29Pôle Gérontologie Clinique, Centre Hospitalier Universitaire de Limoges, Limoges, France
    30. 30First Faculty of Medicine, Univerzita Karlova v Praze, Prague, Czech Republic
    31. 31Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
    32. 32Department of Cardiology and Pneumology, University of Goettingen Medical Centre, Goettingen, Germany
    33. 33Institute on Aging, University of Florida, Gainesville, FL, USA
    34. 34Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
    1. Correspondence to: E Marzetti Centre for Geriatric Medicine (CeMI), Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Rome, 00168, Italy emanuele.marzetti{at}policlinicogemelli.it (or @Emanuel00962649 on Twitter)
    • Accepted 22 March 2022

    Abstract

    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.

    Footnotes

    • Contributors: RB and FL contributed equally to this article as co-primary authors. AC, EM, FrL, MC, MDB, MP, RoB, RC, RRM, SDA, and SDS conceived and designed the study. EM, MC, MT, RaB, and RC wrote the protocol. AJC-J, AJS, AMWJS, AS, AT, BV, CCS, ET, FaL, FrL, IR, LR-M, MM, PVJ, RR-W, and TS coordinated participant recruitment. MT and RC supervised the interventions. HG and RaB designed the statistical analysis plan. AC, AJC-J, EM, and MDB critically reviewed the statistical analysis plan. HG and RaB performed the statistical analysis. TF replicated the statistical analysis. EM and RC drafted the manuscript. AC, CGA, HG, JS, MC, MDB, MK, MP, MT, RR, RoB, SDA, and SvH critically reviewed the manuscript for important intellectual content. RoB and SDS obtained funding. LM and PB provided administrative and technical support. All authors read and approved the final manuscript. EM, FrL, RC, RR, and RoB act as guarantors, accept full responsibility for the work, had access to the data, and controlled the decision to publish. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

    • Funding: This work was funded by a grant from the Innovative Medicines Initiative Joint Undertaking (IMI−JU 115621), which included in-kind support by member companies of the European Federation of Pharmaceutical Industries and Associations (Sanofi-Aventis, Novartis, GlaxoSmithKline, Servier, Astellas Pharma, and Boehringer Ingelheim). The funder had no role in the study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the article for publication.

    • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: The present work was funded by a grant from the Innovative Medicines Initiative Joint Undertaking. AC, AJC-J, AJS, AMWJS, AS, AT, BV, CCS, EM, ET, FaL, FrL, IR, LM, LR-M, MC, MDB, MM, MT, PVJ, RB, RC, RR-W, SDA, SvH, and TS received in-kind support from the European Federation of Pharmaceutical Industries and Associations as part of the Innovative Medicines Initiative Joint Undertaking for the submitted work; CGA is a full time employee of Servier; HG, PB, and RaB are full time employees of Sanofi-Aventis; JS is a full time employee of Boehringer Ingelheim Pharma; MK is a full time employee of Astellas Pharma; RR and RRM are full time employees of Novartis; AJJ-C received grant support from Abbott Nutrition, Fresenius Kabi, and Nutricia outside of the submitted work, and personal fees from Abbott Nutrition, Fresenius Kabi, Nestlè, Nutricia, Pfizer, and Sanofi-Aventis outside of the submitted work; EM received personal fees from Abbott, Nestlè, Nutricia, and Thermofisher outside the submitted work; MC received personal fees from Nestlè outside the submitted work; RC received personal fees from Abbot and Nutricia outside the submitted work; SDA received grant support from Abbott and Vifor Pharma outside of the submitted work, and personal fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Cordio, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma outside of the submitted work; SDS has a pending US patent; SvH received grant support from Amgen, Boehringer Ingelheim, and ZS Pharma outside of the submitted work and personal fees from AstraZeneca, Bayer, BRAHMS, Chugai, Grünenthal, Helsinn, Hexal, Merck Sharp and Dohme, Novartis, Pharmacosmos, Respicardia, Roche, Servier, and Sorin outside the submitted work; TF received personal fees from Bayer, BiosenseWebster, CSL Behring, Coherex Medical, Fresenius Kabi, Galapagos, Janssen, LivaNova, Minoryx, Novartis, Parexel, Penumbra, Roche, and Vifor Pharma outside the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

    • The lead authors (EM, FrL, RC, RR, and RoB) affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as originally planned have been explained.

    • Dissemination to participants and related patient and public communities: The study results will be disseminated to the public through press release, broadcasts, newspapers, and the SPRINTT website (http://www.mysprintt.eu/en/public).

    • Provenance and peer review: Not commissioned; externally peer reviewed.

    Data availability statement

    Anonymised raw trial data can be shared on request to Luca Mariotti (luca.mariotti1@unicatt.it). A data access agreement needs to be signed.

    http://creativecommons.org/licenses/by-nc/4.0/

    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

    View Full Text
    Back to top