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J Frailty Aging. Author manuscript; available in PMC 2016 December 01. Published in final edited form as: J Frailty Aging. 2015 December 1; 4(4): 207–208.
Innovative Medicines Initiative: The SPRINTT Project Emanuele Marzetti1, Riccardo Calvani1, Francesco Landi1, Emiel O. Hoogendijk2, Bertrand Fougère2, Bruno Vellas2,3, Marco Pahor4, Roberto Bernabei1, Matteo Cesari2,3, and on behalf of the SPRINTT Consortium 1Department
of Geriatrics, Neurosciences, and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy
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2Gérontopôle, 3Inserm
Centre Hospitalier Universitaire de Toulouse, Toulouse, France
UMR 1027, Université de Toulouse III Paul Sabatier, Toulouse France
4Department
of Aging and Geriatric Research, University of Florida – Institute on Aging, Gainesville, FL, USA
Keywords frailty; sarcopenia; disability; prevention
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The current healthcare systems are built around the traditional paradigm of patients suffering from a single acute illness. They are therefore largely unprepared to face the increasing demands for health services arising from the expansion of an older population with specific medical needs related to multiple chronic disorders. As a consequence, the medical conditions of a large and growing segment of the older European population are not efficiently managed by the available healthcare services (1). Among these conditions, the geriatric syndrome of frailty has emerged as a significant public health priority. It is defined as a multidimensional condition characterised by decreased reserve and diminished resistance to stressors (2). Such extreme vulnerability exposes the older individual to an increased risk of morbidity, disability, inappropriate healthcare use, institutionalization, poor quality of life, and death. Early detection and prevention of frailty are thus crucial to impede its progression and the development of its detrimental clinical consequences, while ensuring sustainability of healthcare systems of the Member States (3). Unfortunately, to date, no healthcare programmes or pharmacological treatments are available for frail older people. This is largely due to the lack of a precise, universal definition of frailty, linked in turn to the multidimensional nature of the condition. Eventually, the existing gaps in knowledge are reflected by the absence of effective interventions. Such a barrier may be overcome by developing and validating a robust conceptual framework to achieve a practical
Corresponding author: Matteo Cesari, MD, PhD. Faculté de Medicine, Université Toulouse III – Paul Sabatier; 37 Allées Jules Guesde, 31000 Toulouse, France. Phone: +33 (0)5 61145628, Fax: +33 (0)5 61145640, [email protected]. Conflict of interest: All the authors are investigators of the SPRINTT project, an Innovative Medicines Initiative (IMI)-funded project (including partners from the European Federation of Pharmaceutical Industries and Aassociations [EFPIA]). Matteo Cesari has received honoraria for presentations at scientific meetings and/or research fundings from Nestlé, Pfizer, Novartis. Bruno Vellas has served as consultant/advisor for Biogen, GSK, Lilly, Lundbeck, Medivation, MSD, Nestlé, Nutricia, Pfizer, Roche, Sanofi, Servier, TauRx Therapeutics, Novartis.
Marzetti et al.
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operationalisation of frailty. This should precisely define its pathophysiological and clinical foundations, to assist in the design and implementation of specific interventions aimed at restoring robustness and delaying the onset of adverse outcomes. The «Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies» (SPRINTT) project is specifically designed to overcome the existing barriers for an efficient public health intervention against frailty, and promote the implementation of successful aging strategies across Europe. To reach such an ambitious goal, the actions of the SPRINTT Consortium are directed towards the achievement of a consensus among academia, regulators, industry (pharmaceutical and medical devices), and patients’ representatives over:
Author Manuscript
1.
clear operationalisation of the presently vague concept of frailty;
2.
identification of a target population with unmet medical needs;
3.
evaluation and validation of methodologies for implementing preventive and therapeutic strategies among frail elders at risk of disability in the European Union;
4.
definition of an experimental setting as a template for regulatory purposes and pharmaceutical investigations;
5.
identification of biomarkers and health technology solutions to be implemented in clinical practice.
Author Manuscript
The SPRINTT project proposes a novel operationalisation of physical frailty recognising sarcopenia as its central biological substrate. This approach is based on the fact that the physical frailty phenotype overlaps substantially with sarcopenia (4). Indeed, many of the adverse outcomes of frailty are probably mediated by sarcopenia, which may therefore represent both the biological substrate for the development of physical frailty and the pathway through which the negative health outcomes of frailty ensue. Although physical frailty encompasses only a part of the frailty spectrum, the identification of a definite biological basis (i.e., skeletal muscle decline and loss of mobility function) opens new venues for the development of interventions to slow or reverse the progression of this condition. It is noteworthy that all of the components describing the Physical Frailty and Sarcopenia (PF&S) model are measurable and quantifiable. It is thus anticipated that the implementation of such a model will allow the identification of a precise subset of frail elderly citizens whose medical needs are presently unmet.
Author Manuscript
The ad hoc randomised clinical trial (RCT) resulting from the SPRINTT project will translate the PF&S model into a multi-component intervention [combining physical activity, nutritional assessment/counseling and implementation of Information & Communication Technology (ICT) solutions] aimed at preventing incident mobility disability and major negative health-related events. The multi-component intervention proposed is original (such an intervention against the outcome of mobility disability has never been previously tested on a large scale, although built upon solid scientific background and data), relevant (it targets conditions of high prevalence in European community-living older persons), pertinent (it is focused on function, a primary component of quality of life and the one of the most important outcomes in the elderly), feasible (it will be carried out by internationally
J Frailty Aging. Author manuscript; available in PMC 2016 December 01.
Marzetti et al.
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recognised researchers with outstanding experience in the field of PF&S), easily applicable at a population level (thus facilitating the future clinical implementation of the project findings), and scalable (it will validate health technology services and an ICT infrastructure that will enable optimal data acquisition/analysis and clinical decision-making, as well as ensure accessibility to the interventions from the user’s home). The RCT, based on a priori power calculation, plans to recruit 1,500 participants aged 70 years and older (750 per treatment arm), distributed across seven regional coordinating site across Europe and involving nine European Countries. The target population will be comprised of “real life”, non-disabled older persons exposed to increased vulnerability to stressors.
Author Manuscript
The identification of such a population will rely on the three key elements that are at basis of the PF&S operationalisation: •
target organ deterioration (i.e., low muscle mass, measured by dual energy x-ray absorptiometry),
•
clinical manifestation of physical frailty (i.e., weakness, slow walking speed, and poor balance),
•
functional impairment [assessed using the short physical performance battery (sppb].
The main exclusion criterion will be the presence of mobility disability, that is the first step of the disabling cascade, at baseline.
Author Manuscript
Participants will be randomised to either a multi-component intervention or an educational control group. Both interventions will be administered for up to three years. The primary outcome will be the incidence of mobility disability, operationalised as incident inability to walk 400 metres. Secondary outcomes will include: changes in physical performance; ability of selected biomarkers to predict the rate of change in muscle mass & functional capacity; changes in frailty status; changes in sarcopenia parameters; incidence of falls and injurious falls; changes in nutritional status; changes in physical function, cognitive function and mood; changes in utilisation of healthcare services; changes in drug consumption and polypharmacy; changes in quality of life; incident cognitive impairment; mortality rate.
Author Manuscript
To ensure the successful accomplishment of all SPRINTT goals, a unique and robust Consortium has been established that convenes internationally recognised leading experts in the field of PF&S. The Consortium is organised in multiple interacting work-package teams, reassembling academia, members of the European Federation of Pharmaceutical Industries and Associations (EFPIA), and two Small and Medium Enterprises (SMEs). Each participant supports with its own specific expertise the conduction of the SPRINTT workpackages. Each leader/co-leader “tandem” will coordinate a group of experts in specific domains. The expertise of each partner will thus be valorised, and the Consortium activities conducted in the most informed, shared, and appropriate way.
J Frailty Aging. Author manuscript; available in PMC 2016 December 01.
Marzetti et al.
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Acknowledgments Funding: All the authors are investigators of the IMI-funded SPRINTT project (IMI-JU 115621). Marco Pahor is Principal Investigator of the University of Florida Claude D. Pepper Older Americans Independence Center (NIH/NIA P30AG028740).
References 1. Vellas B, Cestac P, Morley JE. Implementing frailty into clinical practice: we cannot wait. J Nutr Health Aging. 2012; 16:599–600. [PubMed: 22836699] 2. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013; 381:752–762. [PubMed: 23395245] 3. Morley JE, Vellas B, Abellan van Kan G, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013; 14:392–397. [PubMed: 23764209] 4. Cesari M, Landi F, Vellas B, Bernabei R, Marzetti E. Sarcopenia and physical frailty: two sides of the same coin. Front Aging Neurosci. 2014; 6:192. [PubMed: 25120482]
Author Manuscript Author Manuscript Author Manuscript J Frailty Aging. Author manuscript; available in PMC 2016 December 01.
J Frailty Aging. Author manuscript; available in PMC 2016 December 01. Published in final edited form as: J Frailty Aging. 2015 December 1; 4(4): 207–208.
Innovative Medicines Initiative: The SPRINTT Project Emanuele Marzetti1, Riccardo Calvani1, Francesco Landi1, Emiel O. Hoogendijk2, Bertrand Fougère2, Bruno Vellas2,3, Marco Pahor4, Roberto Bernabei1, Matteo Cesari2,3, and on behalf of the SPRINTT Consortium 1Department
of Geriatrics, Neurosciences, and Orthopedics, Catholic University of the Sacred Heart, Rome, Italy
Author Manuscript
2Gérontopôle, 3Inserm
Centre Hospitalier Universitaire de Toulouse, Toulouse, France
UMR 1027, Université de Toulouse III Paul Sabatier, Toulouse France
4Department
of Aging and Geriatric Research, University of Florida – Institute on Aging, Gainesville, FL, USA
Keywords frailty; sarcopenia; disability; prevention
Author Manuscript Author Manuscript
The current healthcare systems are built around the traditional paradigm of patients suffering from a single acute illness. They are therefore largely unprepared to face the increasing demands for health services arising from the expansion of an older population with specific medical needs related to multiple chronic disorders. As a consequence, the medical conditions of a large and growing segment of the older European population are not efficiently managed by the available healthcare services (1). Among these conditions, the geriatric syndrome of frailty has emerged as a significant public health priority. It is defined as a multidimensional condition characterised by decreased reserve and diminished resistance to stressors (2). Such extreme vulnerability exposes the older individual to an increased risk of morbidity, disability, inappropriate healthcare use, institutionalization, poor quality of life, and death. Early detection and prevention of frailty are thus crucial to impede its progression and the development of its detrimental clinical consequences, while ensuring sustainability of healthcare systems of the Member States (3). Unfortunately, to date, no healthcare programmes or pharmacological treatments are available for frail older people. This is largely due to the lack of a precise, universal definition of frailty, linked in turn to the multidimensional nature of the condition. Eventually, the existing gaps in knowledge are reflected by the absence of effective interventions. Such a barrier may be overcome by developing and validating a robust conceptual framework to achieve a practical
Corresponding author: Matteo Cesari, MD, PhD. Faculté de Medicine, Université Toulouse III – Paul Sabatier; 37 Allées Jules Guesde, 31000 Toulouse, France. Phone: +33 (0)5 61145628, Fax: +33 (0)5 61145640, [email protected]. Conflict of interest: All the authors are investigators of the SPRINTT project, an Innovative Medicines Initiative (IMI)-funded project (including partners from the European Federation of Pharmaceutical Industries and Aassociations [EFPIA]). Matteo Cesari has received honoraria for presentations at scientific meetings and/or research fundings from Nestlé, Pfizer, Novartis. Bruno Vellas has served as consultant/advisor for Biogen, GSK, Lilly, Lundbeck, Medivation, MSD, Nestlé, Nutricia, Pfizer, Roche, Sanofi, Servier, TauRx Therapeutics, Novartis.
Marzetti et al.
Page 2
Author Manuscript
operationalisation of frailty. This should precisely define its pathophysiological and clinical foundations, to assist in the design and implementation of specific interventions aimed at restoring robustness and delaying the onset of adverse outcomes. The «Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies» (SPRINTT) project is specifically designed to overcome the existing barriers for an efficient public health intervention against frailty, and promote the implementation of successful aging strategies across Europe. To reach such an ambitious goal, the actions of the SPRINTT Consortium are directed towards the achievement of a consensus among academia, regulators, industry (pharmaceutical and medical devices), and patients’ representatives over:
Author Manuscript
1.
clear operationalisation of the presently vague concept of frailty;
2.
identification of a target population with unmet medical needs;
3.
evaluation and validation of methodologies for implementing preventive and therapeutic strategies among frail elders at risk of disability in the European Union;
4.
definition of an experimental setting as a template for regulatory purposes and pharmaceutical investigations;
5.
identification of biomarkers and health technology solutions to be implemented in clinical practice.
Author Manuscript
The SPRINTT project proposes a novel operationalisation of physical frailty recognising sarcopenia as its central biological substrate. This approach is based on the fact that the physical frailty phenotype overlaps substantially with sarcopenia (4). Indeed, many of the adverse outcomes of frailty are probably mediated by sarcopenia, which may therefore represent both the biological substrate for the development of physical frailty and the pathway through which the negative health outcomes of frailty ensue. Although physical frailty encompasses only a part of the frailty spectrum, the identification of a definite biological basis (i.e., skeletal muscle decline and loss of mobility function) opens new venues for the development of interventions to slow or reverse the progression of this condition. It is noteworthy that all of the components describing the Physical Frailty and Sarcopenia (PF&S) model are measurable and quantifiable. It is thus anticipated that the implementation of such a model will allow the identification of a precise subset of frail elderly citizens whose medical needs are presently unmet.
Author Manuscript
The ad hoc randomised clinical trial (RCT) resulting from the SPRINTT project will translate the PF&S model into a multi-component intervention [combining physical activity, nutritional assessment/counseling and implementation of Information & Communication Technology (ICT) solutions] aimed at preventing incident mobility disability and major negative health-related events. The multi-component intervention proposed is original (such an intervention against the outcome of mobility disability has never been previously tested on a large scale, although built upon solid scientific background and data), relevant (it targets conditions of high prevalence in European community-living older persons), pertinent (it is focused on function, a primary component of quality of life and the one of the most important outcomes in the elderly), feasible (it will be carried out by internationally
J Frailty Aging. Author manuscript; available in PMC 2016 December 01.
Marzetti et al.
Page 3
Author Manuscript
recognised researchers with outstanding experience in the field of PF&S), easily applicable at a population level (thus facilitating the future clinical implementation of the project findings), and scalable (it will validate health technology services and an ICT infrastructure that will enable optimal data acquisition/analysis and clinical decision-making, as well as ensure accessibility to the interventions from the user’s home). The RCT, based on a priori power calculation, plans to recruit 1,500 participants aged 70 years and older (750 per treatment arm), distributed across seven regional coordinating site across Europe and involving nine European Countries. The target population will be comprised of “real life”, non-disabled older persons exposed to increased vulnerability to stressors.
Author Manuscript
The identification of such a population will rely on the three key elements that are at basis of the PF&S operationalisation: •
target organ deterioration (i.e., low muscle mass, measured by dual energy x-ray absorptiometry),
•
clinical manifestation of physical frailty (i.e., weakness, slow walking speed, and poor balance),
•
functional impairment [assessed using the short physical performance battery (sppb].
The main exclusion criterion will be the presence of mobility disability, that is the first step of the disabling cascade, at baseline.
Author Manuscript
Participants will be randomised to either a multi-component intervention or an educational control group. Both interventions will be administered for up to three years. The primary outcome will be the incidence of mobility disability, operationalised as incident inability to walk 400 metres. Secondary outcomes will include: changes in physical performance; ability of selected biomarkers to predict the rate of change in muscle mass & functional capacity; changes in frailty status; changes in sarcopenia parameters; incidence of falls and injurious falls; changes in nutritional status; changes in physical function, cognitive function and mood; changes in utilisation of healthcare services; changes in drug consumption and polypharmacy; changes in quality of life; incident cognitive impairment; mortality rate.
Author Manuscript
To ensure the successful accomplishment of all SPRINTT goals, a unique and robust Consortium has been established that convenes internationally recognised leading experts in the field of PF&S. The Consortium is organised in multiple interacting work-package teams, reassembling academia, members of the European Federation of Pharmaceutical Industries and Associations (EFPIA), and two Small and Medium Enterprises (SMEs). Each participant supports with its own specific expertise the conduction of the SPRINTT workpackages. Each leader/co-leader “tandem” will coordinate a group of experts in specific domains. The expertise of each partner will thus be valorised, and the Consortium activities conducted in the most informed, shared, and appropriate way.
J Frailty Aging. Author manuscript; available in PMC 2016 December 01.
Marzetti et al.
Page 4
Author Manuscript
Acknowledgments Funding: All the authors are investigators of the IMI-funded SPRINTT project (IMI-JU 115621). Marco Pahor is Principal Investigator of the University of Florida Claude D. Pepper Older Americans Independence Center (NIH/NIA P30AG028740).
References 1. Vellas B, Cestac P, Morley JE. Implementing frailty into clinical practice: we cannot wait. J Nutr Health Aging. 2012; 16:599–600. [PubMed: 22836699] 2. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013; 381:752–762. [PubMed: 23395245] 3. Morley JE, Vellas B, Abellan van Kan G, et al. Frailty consensus: a call to action. J Am Med Dir Assoc. 2013; 14:392–397. [PubMed: 23764209] 4. Cesari M, Landi F, Vellas B, Bernabei R, Marzetti E. Sarcopenia and physical frailty: two sides of the same coin. Front Aging Neurosci. 2014; 6:192. [PubMed: 25120482]
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