Scientific Bibliography - 19. Randomized Controlled Trial - BMJ

19. Randomized Controlled Trial - BMJ . 2022 May 11;377:e068788. doi: 10.1136/bmj-2021-068788.

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

 Roberto Bernabei  1   2 , Francesco Landi  1   2 , Riccardo Calvani  1 , Matteo Cesari  3   4 , Susanna Del Signore  5 , Stefan D Anker  6 , Raphael Bejuit  7 , Philippe Bordes  7 , Antonio Cherubini  8 , Alfonso J Cruz-Jentoft  9 , Mauro Di Bari  10 , Tim Friede  11   12 , Carmen Gorostiaga Ayestarán  13 , Harmonie Goyeau  7 , Pálmi V Jónsson  14 , Makoto Kashiwa  15 , Fabrizia Lattanzio  8 , Marcello Maggio  16   17 , Luca Mariotti  2 , Ram R Miller  18 , Leocadio Rodriguez-Mañas  19 , Regina Roller-Wirnsberger  20 , Ingrid Rýznarová  21 , Joachim Scholpp  22 , Annemie M W J Schols  23 , Cornel C Sieber  24 , Alan J Sinclair  25 , Anna Skalska  26 , Timo Strandberg  27   28 , Achille Tchalla  29 , Eva Topinková  30 , Matteo Tosato  1 , Bruno Vellas  31 , Stephan von Haehling  12   32 , Marco Pahor  33 , Ronenn Roubenoff  34 , Emanuele Marzetti  35   2 , SPRINTT consortium

Collaborators, Affiliations

Collaborators

  • SPRINTT consortium:

Andeleeb Dahy, Laurent Nicolas, Gianluca Zia, Cinzia Bertuzzi, Sabina De Giorgi, Luca Feletti, Alessandro Loria, Davide Mantovani, Elisa Marchioro, Francesco Mocci, Alberto Sacco, Maria Grazia Varesio, Maxime Billot, Noëlle Cardinaud, Muriel Castelli, Marion Charenton-Blavignac, Cecilia Ciccolari-Micaldi, Thierry Dantoine, Caroline Gayot, Nicolas Giroult, Anael Larreur, Cécilie Laubarie-Mouret, Delphine Marchesseau, Thomas Mergans, Thai Binh Nguyen, Arnaud Papon, Johann Ribet, Isabelle Saulnie, Gabor Abellan Van Kan, Virginie Biville, Lauréane Brigitte, Carole Cervera, Céline Cluzan, Muriel Croizet, Sophie Dardenne, Marie Dorard, Charlotte Dupuy, Emilie Durand, Catherine Faisant, Sophie Guyonnet, Rémi Mauroux, Agathe Milhet, Sylvie Montel, Pierre-Jean Ousset, Cécile Picauron, Gaelle Soriano, Bernard Teysseyre, Sital Harris, Allison Ogborne, Sarah Ritchie, Harriet Sinclair, Lois Tirrell, Caroline Sinclair, Alfredo Cesario, Barbara Cabin, Pim de Boer, Claire Ignaszewski, Ingrid Klingmann, Tina Auerswald, Christof Engel, Anna Franke, Ellen Freiberger, Ulrike Freiheit, Susann Gotthardt, Karin Kampe, Robert Kob, Christine Kokott, Carolin Kraska, Christian Meyer, Veronika Reith, Hanna Rempe, Daniel Schoene, Gabrielle Sieber, Kerstin Zielinski, Nicole Ebner, Michael Benecky, Alejandro Alvarez-Bustos, Cristina Alonso Bouzon, Beatriz Contreras Escamez, Jimmy Gonzales Turin, Olga Laosa Zafra, Myriel Lopez Tatis, Laura Pedraza Sepulveda, Juan Luis Sanchez, Carlos Sanchez Puelles, Juan Álvarez-Santos, Belén Fernández-Jiménez, Jesús Mateos-Del Nozal, Beatriz Montero-Errasquín, Beatriz Ponce-Moreno, Cristina Roldán-Plaza, Alfonso Romera-de Vicente, Vicente Sánchez-Cadenas, Carmen Sánchez-Castellano, Elisabet Sánchez-García, María Nieves Vaquero-Pinto, Sandrine Andrieu, Alessandro Blasimme, Cedric Dray, Emmanuelle Rial-Sebbag, Philippe Valet, Laurence Laigle, Itziar Martinez-Melchor, Belen Surroca, Stefania Ambrosi, Renato Baldoni, Serena Bernabei, Anna Rita Bonfigli, Silvia Bustacchini, Barbara Carrieri, Anna Rita Costantini, Michela Cucchi, Giuseppina Dell'Aquila, Emma Espinosa, Luciano Izzo, Massimiliano Fedecostante, Michela Mannoni, Antonella Mengarelli, Marino Modestino, Emanuele Monterubbianesi, Stefano Piomboni, Antonia Scrimieri, Eddy Severini, Fabiana Mirella Trotta, Lorella Vece, Susanna Venere, Elisa Zengarini, Milan Chang, Hrafnhildur Eymundsdóttir, Ólöf Guðný Geirsdóttir, Steinn Baugur Gunnarsson, Steinunn Guðnadóttir, Alfons Ramel, Konstantín Shcherbak, Gerhard Wirnsberger, Sheena Kao, Romain Barnouin, Lex van Velsenm, Miriam Vollenbroek-Hutten, Christian Asbrand, Sandrine Durand, Florence Joly, Klaus Flechsenhar, Régis Le Lain, Jerome Mshihid, Aurèle Ndja, Ivana Drastichova, Eva Hasaliková, Radim Hucko, Seget Jakub, Monika Janácová, Michaela Kilmková, Martina Parízková, Kristyna Pavelková, Michaela Redrova, Petra Rusková, Michele Basile, Damiano Biscotti, Claudio Boni, Vincenzo Brandi, Marianna Broccatelli, Carilia Celesti, Americo Cicchetti, Hélio Jose Coelho-Junior, Agnese Collamati, Silvia Coretti, Emanuela D'Angelo, Mariaelena D'Elia, Eugenio Di Brino, Giovanni Landi, Anna Maria Martone, Elena Ortolani, Teodosio Pafundi, Cecilia Pantanelli, Anna Picca, Matteo Ruggeri, Filippo Rumi, Sara Salini, Giulia Savera, Elisabetta Serafini, Davide L Vetrano, Fabio Vitale, Elisa Adorni, Fulvio Lauretani, Yari Longobucco, Giovanna Maria Pelà, Sara Tagliaferri, Thomas Rapp, Yves Arrghi, Bastian Ravesteinj, Jérôme Ronchetti, Quittterie Roquebert, Jonathan Sicsic, Nicolas Sirven, Harry Gosker, Jos M G A Schols, Lisanne Schuurman, Nick Smeets, Coby van de Bool, Claire Weling, Katja Hallikas, Marjatta Herranen, Laura Hyvönen, Kirsi Ikonen, Satu Jyväkorpi, Anne Karppi-Sjöblom, Kaisa Karvinen, Tarja Kindstedt, Saana Leirimaa, Hanna Öhman, Kaisu Pitkälä, Anja Punkka, Anna-Maria Saavalainen, Tuulia Salo, Katja Sohlberg, Reijo Tilvis, Annele Urtamo, Hannu Vanhanen, Lucie Bautzká, Tereza Gueye, Ilona Juklíčková, Pavla Mádlová, Helena Mejstříková, Helena Michálková, Eva Klára Novotná, Tereza Vágnerová, Ewa Blaszczyk-Bebenek, Marcin Cwynar, Joanna Czesak, Paulina Fatyga, Malgorzata Fedyk-Lukasik, Tomasz Grodzicki, Paulina Jamrozik, Zbigniew Janusz, Ewa Klimek, Sylwia Komoniewska, Maria Kret, Maciej Ozog, Agnieszka Parnicka, Katarzyna Petitjean, Anna Pietrzyk, Karolina Piotrowicz, Barbara Skalska-Dulinska, Damian Starzyk, Katarzyna Szczerbinska, Borys Witkiewicz, Anna Wlodarczyk, Wieslawa Zgud

Affiliations

  • 1 Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy.
  • 2 Department of Geriatrics and Orthopaedics, Università Cattolica del Sacro Cuore, Rome, Italy.
  • 3 Department of Clinical Sciences and Community Health, Università di Milano, Milan, Italy.
  • 4 Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy.
  • 5 Bluecompanion, London, UK.
  • 6 Department 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 Sanofi-Aventis R&D, Chilly-Mazarin, France.
  • 8 IRCCS INRCA, Ancona, Italy.
  • 9 Servicio de Geriatría, Hospital Universitario Ramón y Cajal-IRYCIS, Madrid, Spain.
  • 10 Geriatric Intensive Care Medicine, Università degli Studi di Firenze and Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
  • 11 Department of Medical Statistics, University of Goettingen Medical Centre, Goettingen, Germany.
  • 12 German Centre for Cardiovascular Research (DZHK) partner site Göttingen, Goettingen, Germany.
  • 13 International Clinical Trial Research Department, Servier, Madrid, Spain.
  • 14 Department of Geriatrics, Landspitali University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • 15 Astellas Pharma, Tokyo, Japan.
  • 16 Department of Medicine and Surgery, Università degli Studi di Parma, Parma, Italy.
  • 17 Cognitive and Motor Centre, Medicine and Geriatric Rehabilitation Department of Parma, University Hospital of Parma, Parma, Italy.
  • 18 Translational Medicine, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
  • 19 Servicio de Geriatría, Hospital Universitario de Getafe, Getafe, Spain.
  • 20 Department of Internal Medicine, Medizinische Universität Graz, Graz, Austria.
  • 21 Silesian Hospital in Opava, Opava, Czech Republic.
  • 22 Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma, Biberach an der Riss, Germany.
  • 23 Department of Respiratory Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Universiteit Maastricht, Maastricht, Netherlands.
  • 24 Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nurnberg, Germany.
  • 25 Diabetes Frail, Droitwich Spa, UK.
  • 26 Department of Internal Medicine and Gerontology, Uniwersytet Jagiellonski Collegium Medicum, Faculty of Medicine, Krakow, Poland.
  • 27 University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • 28 University of Oulu, Centre for Life Course Health Research, Oulo, Finland.
  • 29 Pôle Gérontologie Clinique, Centre Hospitalier Universitaire de Limoges, Limoges, France.
  • 30 First Faculty of Medicine, Univerzita Karlova v Praze, Prague, Czech Republic.
  • 31 Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.
  • 32 Department of Cardiology and Pneumology, University of Goettingen Medical Centre, Goettingen, Germany.
  • 33 Institute on Aging, University of Florida, Gainesville, FL, USA.
  • 34 Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland.
  • 35 Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy This email address is being protected from spambots. You need JavaScript enabled to view it..

Free PMC article

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.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Conflict of interest statement

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.

 

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